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The Magic Cure to Old Age Problems

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Imagine we have developed a medicine that could cure most of the problems that come with aging. If you take it, you have a decreased risk of Alzheimer’s, a better memory, better reasoning ability, plus your brain can heal itself better when damaged. Seems like a pretty good deal! What if I told you that all you had to do was live with some people, play some board games and voluntarily exercise a little bit. Would you be surprised? That’s what research on cognitive research has shown us.

In order to understand exactly what cognitive reserve is, let’s define some of the main components. Brain reserve and cognitive reserve are often used interchangeably when really they are two separate concepts. Brain reserve refers to the number of brain features, like how many synapses and neurons we have and things like the size of actual parts of our brain that allow people to adjust to brain pathology. Cognitive reserve, on the other hand, is how our brain can flexibly adjust to tasks in an efficient manner.

Some animal models have shown us that there are a number of things we can do on our own, without a doctor’s note, to try and decrease our risk of cognitive decline as we age. Some studies have exposed mice to environmental enrichment and found an increase in the number of neurons in their hippocampus, an area of the brain very important in memory. Glial cells, important in supporting the structure of our brain, are found to be created more when rodents participated in physical activity. Environmental enrichment also increased dendritic spine density ( a correlate to memory formation) while physical activity increased angiogenesis, the creation of new blood vessels.

How does cognitive reserve protect us from things like Alzheimer’s?

Part of the pathology of Alzheimer’s is that it makes physical changes in our brain. With people who have higher levels of cognitive reserve, they are able to withstand those changes longer and show fewer symptoms in comparison to those with lower levels of cognitive reserve. Basically, think of cognitive reserve as a mediator between two parties fighting over the future of your brain health. The pathology wants to lead you to a specific clinical outcome and the more mediators (cognitive reserve) you have, the less severe that clinical outcome has to be.

 

This picture sums up how everything we do affects our brain, which then affects our cognitive reserve.

 

Our education, intake of information, and life events can all impact cognitive reserve. Genetics plays a component too. And, as we build more cognitive reserve that can help us withstand some of that cognitive decline that comes with aging.

What should I do?

Every now and then, put down your phone and do something that engages your brain and provides some environmental enrichment. Read a book, play a difficult board game, dance, garden, get some exercise and eat right. All the things you already know you should be doing will help your brain to build up a reserve against decline! I know it can be hard to shut off Netflix sometimes, but trust me, your future brain will thank you.

 

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Neurochemisty- Importance of the Journey

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My time in Neurochemistry has come to an end. It’s been a bumpy ride, full of ups and downs but I think that’s what education is supposed to be. What would I have gained in experience if I could just memorize and recite information with ease? Concordia College makes sure that students are not just learning information to regurgitate back out but actually teaching students to apply their knowledge to the world in a meaningful and impactful way. We call this BREW- Becoming Responsibly Engaged in the World. Neurochemistry has been a class where I have been challenged to think outside the box and not just memorize what I’ve learned (although that’s a component too). I actually know what to do with the information I’ve learned and how to explain the importance to other people. The best way to explain the type of learning experience Neurochemistry has been is to explain how it fits in with Concordia’s 5 goals for liberal learning.   

  1. Instill a love for learning

I’ve always considered myself someone interested in learning, but I think my view of how to learn was too narrow before this class. I paid attention when professors would lecture and took notes when words were bolded in the textbook. However, I rarely had conversations with my peers about their thoughts on the topic and how they understood it. Every Wednesday of the semester, we would each come to class prepared to talk about a topic that others didn’t know about. All of us learned about a different piece of the puzzle and then as a class, we were able to complete the puzzle with our combined knowledge. I loved coming together and being taught something different by each person, especially since everyone has their own unique way of explaining things.

2. Develop foundational skills and transferable intellectual capacities

One of the most important skills we learned in Neurochemistry is how to share information with people who may not have a background on the subject. Sure, we as scientists can make a great discovery but does that matter at all if we can’t share that information effectively? We practiced our narrative skills throughout the semester by writing blog posts and trying to figure out how to concisely explain a 20 page article in 500 hundred words. I hope to attend graduate school and this is a necessary skill that any scientist needs to learn, so better I learn now!

3. Develop an understanding of disciplinary, interdisciplinary and intercultural perspectives and their connections

Neurochemistry by itself means almost nothing. We can understand how things happen on a cellular and molecular level but if we aren’t looking at the bigger picture, whether there’s an influx of calcium or activation of GPCRs, it doesn’t matter. We need to determine the consequences of over or under activation in these signaling pathways and that means taking an interdisciplinary perspective. We need to understand the biology of the body, the psychology of the mind, the chemistry of the signals, and the effects of social interactions to grasp the importance of what we are learning. We can learn about how addiction pathways in the brain are strengthened but if we don’t consider the stigma put on individuals or the barriers to treatment, we aren’t going to solve the problem anytime soon. Taking this class with students from all different majors and having an entire class period dedicated to discussions lead to a breadth of knowledge being shared.

4.  Cultivate an examined cultural, ethical, physical and spiritual self-understanding

We cover heavy topics in class, a lot of which people have been personally affected by. Talking about our opinions can be hard when some of the topics can be political and deeply personal. Our class has had to learn how to strike the right balance when talking about these issues. It requires a lot of thought and reflection. How do we share our opinions without hurting others? We try to approach each topic with an open mind to learn from others. Maybe I have opinion A but I’m open to the possibility of a classmate teaching me why they think opinion B is important. Going in with a mindset like that had helped our class approach topics in a respectful way without having to cross boundaries.

5. Encourage responsible participation in the world

Part of our class this year was to participate in a community action project to assess some of the needs in the Fargo/Moorhead area. After communicating with some local mental health agencies, we decided to target our efforts to incoming first year students. Mental health education is not required in all states and so some freshman come into college with no baseline information about what some signs and symptoms are and how to seek help. We gave presentations to First Year Transition (FYT) Labs and asked students to rank their knowledge before and after the presentation. We hope that the enthusiastic responses we received will encourage the orientation team to incorporate more mental health curriculum when students arrive on campus.

 

Attending a liberal arts institution has given me the opportunity to focus on these 5 goals and be a part of a deeper type of learning. Many students don’t get the opportunity to directly impact their community or to have meaningful conversations about topics like addiction and obesity and I have Concordia to thank for that. If I had to choose one skill that this class has given me, it would be the confidence to step outside my comfort zone. I came into this class very nervous because I wasn’t able to take the prerequisites. With a little extra work and the support of my peers and professor, I had a meaningful and educational experience in this class. It’s pretty rare you get both.

 

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Beyond the Brain, Beyond the Classroom

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If I’m being honest, I wasn’t sure what to expect when I entered my first day of neurochemistry. I knew that it was going to be a more diverse group of students than the average chemistry class, drawing from psychology, neuroscience, biology, and other majors. I had also heard that the structure of the class was not your typical lecture-learn-regurgitate-repeat style that is so often found in the college classroom. Beyond the vague understanding that this class was atypical, I expected a fairly normal semester. Neurochemistry, however, is a class taught in a very non-traditional way and this lends itself particularly well to achieving Concordia’s five goals for liberal learning.

Instill a love for learning

I have always loved learning, to the point that my constant curiosity drove my family crazy.  Nevertheless, neurochemistry did a particularly good job of stoking my curiosity. Lacking in traditionally graded assignments and quizzes, we were warned from the beginning that self-driven learning is a hallmark of the course. I appreciated this method and felt like I was able to thrive. Too often courses get bogged down in completing assignments and endless busy work in the name of racking up points. By removing some of the more rudimentary points from the class, it was easier to relax and focus on working in a style that helped me learn the most. Additionally, I found the majority of topics we discussed to be very interesting. The class’ format of learning basic signaling ideas before using that understanding in the context of disease pathologies made the science more interesting. I also improved my ability to read literature articles, consider what was being presented critically and skeptically, and communicate this information to my peers concisely and accurately. By allowing for ample discussion, the class was able to learn from and teach each other. The limiting factor to this type of learning is that each student only gets out what they put in… and what their peers are willing to give. Overall, the majority of the class was dedicated to learning and improving each week, but there were occasional shortcomings, as is expected. Finally, by replacing traditional tests with neurochemistry “performances”, we were able to show the skills we acquired as the semester went on. By having to critically think about an issue without being handed the whole story, I felt like everyone was given an equal opportunity to succeed and show their skills. Rather than the grade depending on whether you remembered the MAPK pathway, it evaluated critical thinking and overall understanding, which are much more important skills in the long run. Overall, allowing students more autonomy over their education helped instill a love for learning—and neurochemistry!

Develop foundational skills and transferable intellectual capacities

The structure of this class also encouraged its students to develop skills that can be used outside the classroom. Communication was a big focus of the semester, which is a universal skill required across professions. Focusing on condensing our ideas into an “and, but, therefore” structure required us to think past the acronym soup that biochemistry often gets stuck in. Beyond finding interesting narratives, being able to talk about one small technical portion of a paper on our Wednesday “speed dating” classes taught us how to be concise and brief while still getting the point across. This is a particularly valuable lesson for me, as research “elevator pitches” are very common in the world of academia, but difficult to practice and perfect.

Develop an understanding of disciplinary, interdisciplinary and intercultural perspectives and their connections

As a biochemistry and Spanish major, this goal for liberal learning is of particular importance to me. I was able to use my group’s community action project (CAP) to combine these disciplines for have a greater impact on the community. The CAP project is already interdisciplinary in nature due to the partnership between neurochemistry and social work. However, based on my experience doing outreach in Spanish, I though it would be an exciting opportunity to focus our community outreach on the Fargo-Moorhead Hispanic community. By successfully completing an informational session in Spanish at St. Francis de Sales church, we further integrated disciplines across Concordia. By making more connections between STEM, humanities, and languages I continue to shape my perspective of the world and our community in the area.

Cultivate an examined cultural, ethical, physical and spiritual self-understanding

Understanding culture is an extremely important part of learning, whether you’re reflecting on your own culture or learning about another. Friday discussions offered an opportunity for each of us to combine our previous knowledge, experiences, and opinions with the science discussed during the week. In these discussions we were again able to move beyond the classroom and talk about real  issues affecting our school, the community, the U.S., and the world overall. It was interesting to hear and learn of everyone’s different perspectives and opinions. Often times I craved discussions more rooted in research and fact but hearing personal experiences and opinions does have its own merit. Whatever the discussions focused on, having access to so many different perspectives about varied and controversial topics helped improve my own self-understanding of the world.

Encourage responsible participation in the world

In addition to encouraging interdisciplinary work, the CAP project encouraged us to move forward responsibly as we engage with our community. I think the most applicable thing that was driven home by this project was the idea of a assessing the needs of a community rather than offering a group what you think they need. Too often people with the best of intentions cause more hard then good because they fail to evaluate the community they are trying to help. In my opinion, the only way to work in the world responsibly is to recognize that we all have more to learn than we have to teach. Reaching out to different communities in the FM area demonstrated this idea to me again.

That’s All Folks

Whether looked at through the lens of liberal learning or understanding biochemical signaling pathways, it has been a semester full of learning. I have not only improved as a biochemist, but also learned a lot about communication and critical thinking, and to me that is what it means to be a liberal learner. The semester wasn’t without challenges; the CAP was full of setbacks and struggles, discussions sometimes fell short, and pathways became muddled. Nevertheless, I learned a lot this semester, including from the challenges. As I continue my education, I look forward to continuing to improve on the communication and critical thinking skills that I practiced often during this course.  I am excited to weave this course into my narrative, and will continue to look beyond the brain, and beyond the classroom.

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The Controversy about Cannabinoids

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What are Cannibinoids?

Cannabinoids exist naturally in the body as N-arachidnonyl-ethanolamine (AEA) and 2-arachidonylglycerol (2-AG). They bind to two different types of cannabinoid receptors CB1R and CB2R. AEA and 2-AG are produced by the body in response to increases in the concentrations of calcium in the cell. These molecules are different from other neurotransmitters in the brain because they are unable to diffuse freely in the brain and have to rely concentration gradients or transport systems. Cannabinoids can also come from outside the body in the form of cannabis or synthetic cannabinoids who have similar effects on the body as endocannabinoids.

https://www.ncbi.nlm.nih.gov/pubmed/29533978

Endocannabinoid Signaling

The image above gives a good view of cannabinoid signaling. The cannabinoid receptor is a G-protein coupled receptor and when it is bound to the G protein, which in this case is an inhibitor or can regulate enzymes and channels. As seen in the graphic it inhibits adenylyl cyclase and its downstream effects, activates ERK which slows the cell cycle, and through the actions of ceramide it can inhibit AKT and mTOR which have a role in cell death. This particular graphic is focused on the role of endocannabinoids in cancer patients so this is where the halting of tumor progression via the actions of RhoA and the inhibition of the cell cycle resulting from the activation of ERK is important in the disease progression and treatment through cannabinoids.

https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(13)00044-8

Cannabinoids for Disease Treatment

There are currently three canabionoid derived medications that are approved by the FDA for disease treatment. Epidiolex is a drug that has been approved for the treatment of seizures that are related to Lennox-Gastaut Syndrome and Dravet Syndrome. There is also a wealth of anecdotal evidence about the efficacy of people using cannabis derived products for the treatment of epilepsy. Other drugs have been approved to treat weight loss that is associated with anorexia and with AIDS. Research is also ongoing about the use of these drugs to treat weight loss in cancer patients.

https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd

Thee has also been some research suggesting that cannabis derived products can block the pain pathway and might be a solution for people suffering from chronic pain. Some research has also looked a the treatment of movement disorders, including those seen as a result of Parkinson’s, Multiple Sclerosis, and tardive dyskensia and found that the cannabis derived products can help reverse some of the uncontrollable movements that are seen in these disorders.

https://www.ncbi.nlm.nih.gov/pubmed/29533978

However, as the feature image on this post suggests there is concern about the potential for side effects as a result of the use of cannabis-derived products. These concerns include a potential for an increase in the number of seizures, memory impairments, paranoia, and depression. However, because cannabis is listed as a schedule 1 drug by the DEA this limits the amount of research that can be conducted. Schedule 1 implies that there is no medical use for the drug and implies that there is no use in studying potential medical uses. This limits the amount of studies that can be done on the use of cannabis-derived products and our understanding of their effects.

Disease/Health

Cognitive Reserve – The Retirement Funds of the Brain

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Aging.

It’s a word that most of us don’t like to think about. For some, the idea of growing older is a scary thought, and for others it exists only in the back of the mind until the future arrives. Bottom line is, aging often gets a bad rap. And here’s a shocker – just like you, your brain ages, and once it hits its own point of “retirement,” the natural cognitive decline associated with aging is, unfortunately, irreversible.

End of story? No! You probably didn’t come to this article to hear about all the bad stuff that comes with this natural, inevitable process, so what’s the deal? Well if you haven’t guessed yet, there is one aspect of getting older that many of us look forward to. Yup, that’s retirement. We might dream about our future selves living carefree lifestyles – never-ending days of no work, lounging around at home, or worldwide traveling without a care in the world. But in order to achieve this lifestyle, there is (like in everything else) a monetary factor. You might be familiar with the concept of retirement funds and how important they are for making the future as comfortable as can be. As for your brain, fortunately, recent research suggests that there are numerous activities that can enrich your thinker and significantly lessen the impacts, or at least slow the effects of, cognitive decline and even neurodegenerative pathologies. As it turns out, being exposed to more of these things early on builds into a special “reserve” (almost like a retirement fund!) that the brain can draw from to function more ‘comfortably,’ if you will, even as it enters its own stage of retirement. So let’s get to it!

The Brain’s Reserve – What is it?

What is the brain’s existing resource bank?

Your brain’s reserve can be divided into two categories – cognitive reserve and brain reserve. Though they are quite similar and both beneficial in the long run, the differences between the two should still be noted.

  • Brain Reserve – The available “hardware” (neurons, brain cells, mass, matter, connections, overall volume, etc) your brain has. Like most things, more is usually better. Harvard Medical School gives this useful analogy: “Just like a powerful car that enables you to engage another gear and suddenly accelerate to avoid an obstacle, your brain can change the way it operates and thus make added resources available to cope with challenges.”
  • Cognitive Reserve – Your brain’s ability to use existing “hardware” in the brain reserve to cope with or adapt to changes, such as those seen in neurodegenerative diseases or age-related decline. Below are some examples of cognitive reserve functions that can be boosted by enriching the brain’s neuroplasticity (capability to change)
    • Adult neurogenesis – Formation and differentiation of new neurons, even into adulthood (previously believed to be possible only in children).
    • Gliogenesis – Proliferation of supporting, non-neuron brain cells (glial cells) that can help with cleaning up waste, adding structural support, and protection.
    • Angiogenesis – Generation of new blood vessels that can increase blood supply and thus oxygen to the brain.
    • Synaptogenesis – A form of neuroplasticity where existing neuronal ‘connections’ (synapses) are modified, or more synapses are formed. This is what you think of when you hear more brain connections.

To learn more about cognitive and brain reserve, visit this article here.

The link between the two is quite clear – available brain reserve can allow for more cognitive reserve functions to take place, and increased cognitive reserve can help build on to brain reserve. It makes sense, really. If brain matter and neuronal synapses are lost with cognitive decline, then having more “stuff” for the brain to work with will mean less information lost when things start falling apart, and an increased capability to use what’s left to make up for the loss. In neuroscience terms, the building a brain reserve is “neuroprotective” (quite literally ‘protects the brain’) against the effects of such degeneration.

Just like a powerful car that enables you to engage another gear and suddenly accelerate to avoid an obstacle, your brain can change the way it operates and thus make added resources available to cope with challenges.

Building the Reserve

What are some ways we can build our brain’s available resources?

Great, so now you’re probably wondering – how can I ‘add funds’ to my brain’s reserve, so I can save for those rainy days? Luckily, there are many different forms of enrichment that can help the brain add hardware and increase its adaptability. Although a part of brain reserve is genetic (how much brain capacity and matter you’re born with), research on animal models increasingly points towards the importance of an enriched environment. Continuously doing these activities throughout one’s life can help enhance the reserve:

  • Physical exercise – voluntary exercise has been found to increase cell proliferation and survival rates in the brain by enhancing the production of brain growth factors, called neurotrophins. Works best when paired with a good diet.
  • Bilingualism – learning a new language is no easy feat, but that’s why it’s so good for your brain! Lifelong bilingualism has been found to decrease the effects of Alzheimer’s and general cognitive decline. In fact, in some studies, bilingual individuals with severe atrophy in the brain were found to out perform monolinguals with less atrophy in cognitive tasks!
  • Education and Cognitive Training – This one’s pretty obvious. The more you use your brain, the stronger it gets. Being a lifelong learner constantly stimulates your brain to make new synapses and utilize its hardware for storing information and memories. Though not 100% proven, other mentally stimulating activities such as reading and doing puzzles has been associated with building the reserve. Learning is associated with better cognitive, memory, and language capacity into old age.
  • Social engagement – Meaningful social engagement that allows for self-expression is shown to be a crucial part of an enriched environment. This can mean anything from engaging with friends, being part of a group or team, or participating in consistent volunteer or charity work. In some studies, those who were divorced, widowed, or single were found to have a higher likelihood of developing Alzheimer’s or dementia.
  • Music and learning an instrument – They say music is like another language, and that holds true for the cognitive reserve as well. Learning an instrument is a mentally stimulating task that can help build your reserve.
Learning another language is a great way to stimulate the brain and build neuronal connections.

And that’s definitely not all. For more about building the cognitive reserve and its neuroprotective effects, you can visit this handy article here.

The Reserve at Work

The bottom line is, keep the brain busy, and it will grow. But how does all this magic happen? The mechanisms and proposed pathways that occur in building the reserve are numerous and depends on the type of enrichment, but most of them have been linked to boosting levels of neurotrophins, which are crucial in growth and development of the brain, and to some extent regulating the neurotransmitters (communicating substances of neurons). For example, physical activity requires high energy metabolism, which places demands on the liver. Mitochondria (yes, the powerhouse of the cell!) in liver cells work hard to metabolize energy, and in doing so create a substance called DBHB (a type of ketone). This is not only used as an energy source of the brain, but has also been found to promote gene transcription of BDNF (a type of neurotrophin) by blocking an enzyme that would normally down regulate the process (if you’d like to learn more about the DBHB hypothesis, refer to the link above, in ‘Physical exercise’)!

With that said, it’s no surprise various studies show that those who invested into building their cognitive reserve displayed less cognitive decline, even in patients with Alzheimer’s, dementia, and even Parkinson’s and other usually fatal pathologies. We are quick to consider all the inevitable negatives that come with such disorders and diseases, but the cognitive reserve gives us hope that something out there exists to combat the outcomes.

But whether a dementia patient or a college-age student, everyone can benefit from enriching their mind. At the end of they day, the body operates on a very much “use it or lose it” basis, and unfortunately, that holds true for the brain as well. But by stimulating and giving the brain more resources to work with, even well into its own days of retirement, we can have some peace of mind in knowing that not all is lost with the passage of time.

 

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Summiting Liberal Learning

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I didn’t know what to expect going into neurochemistry this semester. I had no experience in the neurosciences and had never taken a chemistry class without a lab. To say the least, what expectations I did have for this class were blown out of the water and this became one of the most enjoyable classes I have taken at Concordia.

In a short time, I went from knowing nothing about neurosciences to craving more of the specifics about neurochemical pathways. The neat thing is that everyone in our class was the same way. We were all genuinely curious which fostered a unique learning environment. On Wednesdays we would have speed dating rounds where we would each share something regarding the weekly topic that we had researched further. As a group there was so much energy in the room as we shared information and learned more together, it was invigorating. Neurochemistry definitely heightened my love of learning as I always wanted to know more.

Image from https://themindblower96.wordpress.com/2015/05/21/54/.

Each week we read an article outlining the pathology and neurochemistry surrounding a neurological disease or other neurological functions. We would try to understand what we could individually and then discussed the article in class to learn about areas in the paper that were more difficult. Scientific literacy is a transferable skill that will be important in my future endeavors. I might even go as far to include scientific literacy on my resume. My future goal currently is to study plant biology, in which understanding research in the field is critical as it is in all the sciences.

On Fridays, we would sit in a large circle and discuss the topic that our paper covered and other social implications that surround the topic. This was a great way to observe other perspectives in the class but also gave us the opportunity to move away from the microscopic neurochemistry to the macroscopic implications a neurological disorder, substance abuse, or obesity has on society. We were given the opportunity to share our own experiences and biases in an open, accepting zone. I think these discussions were really a time to draw from other disciplines as we analyzed what we knew about the topic. Discussions often included political, ethical, cultural, and social concerns showing that this class provided a wholesome learning experience.

Lastly, a project that we mostly did outside of class was the Community Action Project. In this project we teamed up with social work students to tackle a societal issue with components of neurochemistry. We were each assigned a topic. My group was addiction and we decided to tackle youth vaping. We held four sessions with middle school students who had been cited for vaping. Not only was the project interdisciplinary, as we worked with social work students, but it also allowed us to contribute to the community in one way or another. I’m not sure the middle school students will quit vaping tomorrow but maybe we gave them some things to think about when they do vape. I consider this as the BREW component of our class. We were engaged in an issue that is a part of our world and hopefully were able to contribute to fixing the problem. The addiction counselor at the school will be implementing a similar program in the future with students which makes it feel like we really did contribute.

Neurochemistry was a class that I think embodies the liberal arts education. The course provided a wholesome learning experience through the discussions we had and the Community Action Project. Overall, the class is very creatively administered which is refreshing when most courses in the sciences are lecture based. I thoroughly enjoyed this class and cannot praise the applicability of this class to liberal learning enough. This is liberal learning at its finest!!

-Emma Chandler 2020

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Don’t Get Lost in the Weeds – What’s the Real Deal Behind Marijuana?

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To legalize or not to legalize?

That is the question that often comes to mind when we see that all-too-distinct 7-point leaf. The use of marijuana, or cannabis, has remained a controversial topic in the States over the past years. Whereas some see legalizing cannabis as a stinkingly massive, scary issue, others see it as a sort of “Miracle Drug” – one that has potentially beneficial, yet often overlooked uses. With a nation that’s become keen on broadcasting the dangers of the drug war and “gateway” substances whilst preaching “Pugs Not Drugs” to children (starting as early as elementary school), it becomes quite easy to see how stigmas grow and understand why many often jump to believe the former argument. But without getting lost in the ‘weeds’ – that is, outside of the social stigma, the politics, and the stereotypical associations that come with any type of cannabis use – does cannabis have physiological benefits that would warrant it as the Miracle Drug that many claim it is?

Without further ado, let’s delve into some of the recently researched science behind this Miracle Drug and see if it really does hold up to its controversial nickname.

Weeding Out The Fluff – Endocannabinoids and the Body

Down to core, cannabis is a drug – a chemical that has affects on the body. Claims that cannabis can be used to treat seizures, cancer symptoms, and even neurodegenerative disorders stems from the particular effects it causes. Throughout the body, there is widespread distribution of a special type cell receptor, called an endocannabinoid receptor (CB1 and CB2, two subtypes of CBRs, for short), and CB1 receptors are especially common in the brain. Normally, the body produces lipid-based, endogenous, cannabinoid-like substances called endocannabinoids, which help regulate some processes that occur in the brain via interactions with these receptors (yes, your body synthesizes biological CBD). Thus, plant-derived cannabinoids and synthetic cannabinoids can also interact with these CBRs and produce similar effects. But to understand these, it’s first important to look at what the effects of endocannabinoids.

What are these effects? Because CB1 is so widely dispersed, it can be hard to pinpoint just one. To the right are a few of the many affects cannabinoids can have throughout the body:

Zou, S., & Kumar, U. (2018). Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system. International journal of molecular sciences, 19(3), 833.

But let’s talk about the brain. Normally, CB1 receptors are found on the surfaces of neurons, in especially high concentrations within portions of the brain dedicated to memory, such as the hippocampus. Now for some basic neuroscience. Many types of neurons can be divided into two basic classes: excitatory and inhibitory. Excitatory neurons release communicating molecules, neurotransmitters, to the next neuron. These neurotransmitters are (you guessed it) excitatory, in that they excite the next neuron so it can fire a signal off to whatever its target is – another neuron, a cell, a muscle, you name it. Inhibitory neurons also release neurotransmitters, but in contrast these prevent, or ‘inhibit’ the next neuron from firing or cell from acting, living up to its name. For a basic rundown of excitatory and inhibitory neurotransmitters, check out this video:

Cannabinoids enter the scene in synapses, the space between two neurons where the previous neuron releases its neurotransmitters into, in order for the second to receive and respond to them. From there, they can perform two different feedback processes, depending on the type of neuron (excitatory or inhibitory) – Depolarization Induced Suppression of Inhibition (DSI) or Depolarization Induced Suppression of Excitation (DSE). Though these might sound complicated, their names basically give away their action. Here’s a simplified rundown of DSI:

  • After being activated (in neuroscience terms, ‘depolarized’) the first neuron, an inhibitory neuron, releases inhibitory neurotransmitter (such as GABA), into the synapse.
  • The inhibitory neurotransmitter prevents the downstream neuron from firing by binding to its respective receptors on this neuron. This binding induces a series of biochemical events that makes the neuron much less likely to fire.

Still with me? Up to this point, the first neuron has quite literally inhibited the second neuron. But we don’t want this to last too long – neurons have to fire at various levels in order to carry out their function, form memories, and communicate! So what happens next?

  • Over time, high-frequency inhibitory firing from the first neuron activates regulatory calcium channels on the second neuron, so calcium enters the second neuron.
  • Increased calcium concentration activates an enzyme in the downstream neuron, called phospholipase C (PLC).
  • PLC takes phospholipids from the cell membrane and creates diacylglycerol (DAG)
  • Another enzyme, DAG Lipase, acts on DAG to create whoolah…
2-AG. The name is so long I won’t even bother spelling it out here

A substance called 2-AG. This is that biological endocannabinoid. What does it do next?

  • 2-AG is released back into the synapse, from the downstream neuron, as a “retrograde” (backwards communicating) signaling molecule.
  • The endocannabinoid reacts with our friends, the CB receptors, on the first neuron.

This can set off a variety of chemical cascades, but ultimately it results in less inhibitory neurotransmitter being released. So what happens when you stop inhibiting the second neuron? It is allowed to fire. Thus, the process lives quite literally up to its name – a “Depolarization (Firing) – Induced Suppression of Inhibition.” If you could guess, a DSE does practically the same thing, except the first neuron is excitatory, so suppressing it would lead to more inhibition and less firing of the second neuron (although DSI is more relevant when talking about CBD).  These processes are important in making sure signals don’t run too rampant, or the brain isn’t inhibited for too long, but they are relatively short-lived and thus don’t cause any significant changes in the brain. If you’re more of a visual learner, here’s the entire process in one lovely diagram:

Outline comparing retrograde signalling (DSE, DSI) to regular plasticity in the brain (the process by which synapses, neuronal ‘connections’ change

Putting the ‘Can’ in Cannabis – Beneficial Uses for CBD

Cannabis kept for medical research

So back to cannabis – when you put more endocannabinoid analogs into the synapse for longer periods of time, what happens? Well, depending on whether the process is DSE or DSI, there could be too much or too little excitation or inhibition in various parts of the brain, which could have various effects. Sounds very vague, and it is, but then again it’s nearly impossible to pinpoint what specific part of the brain CBD acts in at one moment in time, and thus what downstream effects are attributed to it (in part due to the widespread nature of CB receptors). Some of the effects are pictured above, but because of the neuro-basis mechanism of cannabis, it’s come into the light of neurodegenerative disease treatments.

Wait a minute, isn’t cannabis psychoactive? How can it be used to treat some of the most vulnerable patient population? In reality, synthetically created CBD is often contaminated with other chemicals and does NOT contain THC, making it a full agonist (interacts fully) with CB receptors and to some extent producing unpredictable and more intense effects. On the other hand, what is often considered “medical marijuana” is plant-derived and exists in the more pure phytochemical state. This form contains THC, making it only a partial agonist for CB receptors, thus producing milder, more natural effects that would normally happen when the body produces endocannabinoids. Here are some potential benefits CBD CAN hold for specific patients:

  • Parkinson’s Disease: In this degenerative disease, neurons that release regulatory neurotransmitter dopamine are damaged over time. Dopamine is largely excitatory, and is important in maintaining smooth motor movement. Thus, using CBD to induce DSI (allow for more excitation in the brain) can make up for some of the excitation lost from losing dopaminergic neurons.
  • Alzheimer’s and Cognitive Decline: A disease marked by slowing memory and mental ability, neurons in areas of the brain relevant to memory are damaged over time in Alzheimer’s. Because they are damaged, they cannot fire the usually excitatory neurotransmitters (such as glutamate) needed for learning and forming new neuronal ‘connections’ (synapses!). Using CBD can again induce DSI and increase excitation in these parts of the brain, potentially improving cognitive ability.
  • Seizures and Epilepsy: Though not directly CBD, a similar derivative of CBD called cannabidiol with lower affinity for CB1 and CB2 receptors has been found to be effective in reducing seizure activity. It is suspected that this derivative “counteracts” DSI, producing less neuronal activity and activation, which could play into reduction of the overactivity seen in many seizure cases. The research can be found here.

And that is definitely not all. Patient cases where CBD has been used to treat anything from pain to cancer-related appetite loss have shown increased quality of life for the users. Nonetheless there is still much research to be done in order to fully discover the mechanisms and reasons behind the beneficial findings detailed in the papers above. However, as marijuana is currently a Schedule 1 drug in the US (a completely different issue I won’t get into today), conducting adequate research on CBD is extremely difficult, and with that the “Miracle” remains unknown for much of society.

On its own, marijuana doesn’t sound so bad – research exists that shows its pure derivative can treat anything from general pain to ultimately fatal neurodegenerative disorders. What’s standing in the way? It’s a complicated, multi-faceted issue that brings into play politics, social stigma, elementary education, and the policies of our current drug industry, and I can say that we are a long way from changing. Who knows, maybe a future with cannabis isn’t such a bad thing. But until word on the street starts welcoming discussion of this Miracle Drug, I guess ‘weed’ never know.

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Got enrichment?

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Enrichment. I associate this word with study hall because the teachers of Absarokee Highschool thought it was a clever way to get students to actually study. Really enrichment is improving or enhancing the value of something. Now, whether calling study hall “enrichment” improved the quality of my education is debatable but, recent research has found that enriching experiences modify the structure of the brain. This is called brain plasticity. Experiences change the nervous system structurally and functionally, and effectively produce a protective reserve that sustains brain function with aging and the onset of diseases.

There are two kinds of protective reserves, brain and cognitive. Brain reserve is the physiological qualities of the brain such as the number of neurons and synapses and the molecular processes maintained by the brain. Cognitive reserve, on the other hand, is the psychological ability to make use of the brain reserve. Building and preserving these reserves protects the brain from deterioration or malfunction of neurochemical processes.

Cognitive reserve is preserved through social, mental, and physical engagement. Research on social interactions such as marital status, living arrangement, parenthood, and friendship have shown to have protective effects on the cognitive reserve. Similarly, activities that are mentally demanding, high education, and complex work are protective of the cognitive reserve as well. Physically, regular exercise and a healthy diet rich in antioxidants and unsaturated fatty acids has been associated with the decreased risk for dementia.

Brain reserve is primarily tested in animal models, as it encompasses the actual anatomy of the brain. In many studies, environmental enrichment induced brain plasticity through cellular and molecular changes. Cellularly, enrichment fosters neurogenesis, gliogenesis, angiogenesis, and synaptogenesis.

  • Neurogenesis: The generation of new, functional neurons
  • Gliogenesis: The generation of astrocytes, which provide structural and functional support to neurons, oligodendrites that facilitate neurotransmission, and microglia that dispose of waste material creating space for neurogenesis.
  • Angiogenesis: The formation of blood vessels
  • Synaptogenesis: The formation of synapses for neurotransmission

At the molecular level, enrichment changes gene expression of certain proteins. These changes facilitate changes in concentrations of neurotransmitters and neurotrophins. Neurotransmitters are involved in the neurotransmission across synapses. Neurotrophins are central to growth and proliferation. Interestingly, there has been some variability in the location in the brain and how neurotransmitters and neurotrophins increase. For the most part, neurotrophins increase; however, neurtransmitters and the receptors there of are not as definitive.

Now that we know what enrichment does, what is enrichment? As mentioned in the cognitive reserve section, neuroprotection is based on social, mental, and physical factors. These three areas are considered the components of enrichment. For testing animal models, treatment groups are afforded social interaction through placing multiple organisms in one confinement. Mental enrichment is applied by allowing the animals access to objects that the organisms can forage for or use in one form or another. Finally, the physical component of enrichment is applied by the type of diet afforded the animals and the access to exercise, such as the size of the confinement and exercise machines.

Increased enrichment resulted in increased neuroprotection through the cellular and molecular processes discussed up above. Enrichment occurs through social, mental, and physical engagement. Neuroprotection can decrease cognitive decline with age and as a result of a degenerative brain disease. Therefore, enrichment is GOOD!

Maybe my teachers were on to something, in calling study hall enrichment. Although, I think all my classmates can attest that high school “enrichment” lacked social interaction as we were not allowed to talk, mental engagement unless you worked on homework, and physical enriching as food and moving was not allowed. So maybe anti-enrichment is a better word?

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Cognitive Reserve and Neurodegenerative Disorders

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What is cognitive reserve?

The terms brain reserve and cognitive reserve are often used interchangeably, however, there is a difference between the two. They are sometimes categorized as passive and active models. Brain reserve is a passive model. It is the size of the brain and its neural components. Individuals have different capacities of brain reserve. These differences lead to differences in how different degrees of brain damage is expressed. Cognitive reserve, on the other hand, is an active model. Cognitive reserve suggests that the brain actively tries to adapt or cope with damage by utilizing pre-existing cognitive processes or by using compensatory processes. With this idea, someone who has more cognitive reserve may be able to tolerate more damage before showing any impairment than someone with less cognitive reserve, even if they have the same amount of brain reserve capacity.

Exposure to environmental enrichment can be beneficial to brain reserve. Enriching factors may include high educational level, complex work, and large amounts of mentally demanding activities. Environmental enrichment has been shown to increase neurogenesis, gliogenesis, angiogenesis, and synaptogenesis in hippocampal and neocortex regions.

Cognitive Reserve and Alzheimer’s Disease

Cognitive reserve has been shown to mediate the clinical manifestations of Alzheimer’s disease (AD). One study looked at AD patients with higher education levels and lower education levels and the differences in different abilities. They saw no difference between groups with the preservation of verbal abilities. They did notice, however, that higher education patients had better preserved visuo-spatial abilities, logical deductive reasoning, constructional praxis, and executive functions. Lower education patients had reduced grey matter volume when compared to higher education patients.

Bilingualism can also increase cognitive reserve. Studies indicate that bilinguals can compensate for more severe changes from early phases of AD than monolinguals.

 

Cognitive Reserve and Parkinson’s Disease

There has been a greater interest in research regarding cognitive reserve and Parkinson’s disease (PD). Again, like as in Alzheimer’s disease, studies suggest that higher levels of education as a proxy for cognitive reserve has significant associations with the performance of cognitive tests in PD.

Though bilingualism has been shown to delay clinical manifestations in AD, it has not been well studied with PD. The first study to look at this found no significant difference between monolinguals and bilinguals with PD in the performance of executive function tests.

Research between cognitive reserve and neurodegenerative diseases like AD or PD is limited. Further studies need to be conducted to come to any further conclusions on how cognitive reserve impacts brains of these patients.

 

 

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739591/

https://go-gale-com.cordproxy.mnpals.net/ps/retrieve.do?tabID=T002&resultListType=RESULT_LIST&searchResultsType=SingleTab&searchType=AdvancedSearchForm&currentPosition=1&docId=GALE%7CA257676398&docType=Report&sort=RELEVANCE&contentSegment=ZEDU-MOD1&prodId=PROF&contentSet=GALE%7CA257676398&searchId=R1&userGroupName=mnacarlb&inPS=true

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831977/

https://www.hindawi.com/journals/pd/2015/943572/

https://www.prd-journal.com/article/S1353-8020(13)00304-0/pdf

Image source:

https://www.health.harvard.edu/mind-and-mood/what-is-cognitive-reserve

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Ins and Outs of Endocannabinoids

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Marijuana or cannabis. Some say it is bad, others say its good. Lets dive down deep to discover the ins and outs of the endocannabinoid system.

Cannabis is a plant that is grown and yields CBD and THC. THC activates cannabinoid receptors and leads to the common high due to the psychoactive component. More is still being learned about CBD, and it is known that it is use as a treatment option for pain. THC uses two different receptors to bind, CB1R and CB2R. CB1R is dominant in brain and skeletal muscle whereas CB1Rb has higher expression within the liver and pancreatic cells due to its involvement in metabolism. CB2R are found in the testes and lower levels in brain reward regions. Endogenous agonist (AEA) and 2-AG are important endocannabinoids that bind to both receptors.  AEA has a high-affinity and partial agonist of CB1R and inactive to CB2R. 2-AG is a full agonist against both receptors, but has a low affinity. CB1R can inhibit GABA and glutamate release from presynaptic terminals meaning it can modulate neurotransmission. This is important because CB1R plays a neuroprotective role against excitotoxicity, inhibits nitric oxide, and increases brain derived neurotrophic factors (BDNF). So how is this all beneficial or hurtful to the body?

CB1R has been observed in a variety of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s. In Parkinson’s, there is an upregulation of CB1R and the endocannabinoid system. In Huntington’s, there is a progressive loss of CB1Rs and worsens over time. Currently, CB1R is being looked at as a way to control appetite. The most common use of cannabinoids however is for pain. In cancer patients who are undergoing chemotherapy or radiation, they typically experience a loss of appetite. Cannabinoids are being used to help increase their appetite to maintain a healthy weight to continue treatment and increase their well being. Along with stimulating appetite, it also reduces nausea, vomiting, and alleviates pain. As mentioned above, one property of endocannabinoids is the neuroprotective effects against excitotoxicity. This is commonly associated with seizures due to the over active firing. Endocannabinoids can reduce this, resulting in dramatic decreases for those that have epilepsy. In fact, some families who have young children with severe epilepsy will move to a state that has legalized medical marijuana. In moving to these places, these families have had children or family members go from hundreds of small seizures and frequent gran mal seizures to less than a quarter of that. This shows that the endocannabinoid system can drastically reduce neurological diseases and their symptoms to increase the way of life of these people. However, there are some fears that are associated with endocannabinoids such as the addictive or gate way drug tendencies. However, cannabis does not actually have an addictive chemical like nicotine. Cannabis is considered a gateway drug but not a lot of research has been done, in fact, alcohol a frequently consumed item is considered a gateway drug.

The endocannabinoid is a complex system that is still being studied for pros and cons. A lot of the research that is now available is leaning towards more benefits than harms, especially for neurodegenerative diseases in which this system can help improve the quality of life.

 

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