Alzheimer’s Disease and Diet as Prevention

What is Alzheimer’s disease?

Alzheimer’s disease (AD) is a neurodegenerative disease that causes the brain to shrink and brain cells to die. It is characterized by memory loss and decline in social skills and behaviors. Cognitive decline is gradual, so in the early years of AD, people may forget recent events or little details, but it can lead to declines in memory where people cannot do everyday tasks on their own. Around 6.5 million people living in the United States suffer from AD and it is projected to impact much greater numbers in the future. [1]

What is happening in the brain?

The exact cause of AD is not fully understood by scientists, but researchers have found two hallmarks of AD in the brain. One being beta-amyloid plaques which are clumps of fragments from proteins that block communication between cells in the brain. The other is neurofibrillary tangles made by tau proteins which also disrupt communication between cells but also cause damage to cells in the brain. [1]

[2]

Insulin resistance and Alzheimer’s disease

Insulin signaling is important for regular neurological functioning; insulin improves things like memory and other cognitive functions. Insulin resistance refers to the brain’s decreased sensitivity to sensing insulin resulting in defects in insulin signaling. This could lead to an increase in neuroinflammation and oxidative stress which eventually lead to neurodegeneration. Insulin resistance and reduced insulin signaling is believed to cause the formation of the beta-amyloid plaques and neurofibrillary tangles that are believed to be the root cause of AD. [3]

How can diet prevent Alzheimer’s disease?

Eating healthy foods can prevent neuroinflammation and oxidative stress, which are risk factors for AD. A healthy diet can increase nutrient intake which can increase anti-inflammatory and antioxidant activity in the brain, protecting the brain against neurodegeneration. A healthy diet can also decrease the risk of developing diabetes, obesity, and heart disease which are found to be risk factors for developing AD. [4]

Mediterranean and MIND diets

The Mediterranean diet emphasizes the consumption of plant-based foods and healthy fats. Fruits and vegetables are essential to this diet as well as whole grains, fish, and unsaturated fats. The Mediterranean diet consists of low levels of red meats and sugars. The MIND diet is a spin on the Mediterranean diet with the DASH diet (diet to help treat and prevent hypertension). It has been found through studies that treating high blood pressure has positive effects in reducing the risk of dementia. The MIND diet is very similar to the Mediterranean diet but greatly emphasizes the intake of vegetables and fruits, but especially leafy greens and berries. Fish and whole grains are essential parts of the MIND diet as well as limiting the intake of red meat, cheeses, sugars, and fried foods. Studies on the MIND diet in relation to dementia and AD have shown that people who reported sticking to the MIND diet or the Mediterranean diet showed less evidence of beta-amyloid plaques and neurofibrillary tangles, and they found that it reduced the risk of developing AD by 53%. [5]

[6]

What does this mean?

Specific diets could have a positive effect on retaining cognitive function and preventing the development of AD, but more research and evidence needs to be conducted to prove this for sure. What we do know is that having a healthy lifestyle which includes eating a healthy diet has been proven to prevent cognitive decline which could be related to the prevention of AD.

 

References

[1] Mayo Clinic. (2024, February 13). Alzheimer’s disease. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/symptoms-causes/syc-20350447. 

[2] Alzheimer’s Disease Research. (2015, July 1). Amyloid Plaques and Neurofibrillary Tangles. BrightFocus Foundation. https://www.brightfocus.org/news/amyloid-plaques-and-neurofibrillary-tangles.

[3] Akhtar, A. & Sah, S. P. (2020). Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer’s disease. Neurochemistry International, 135, 1-11. https://doi.org/10.1016/j.neuint.2020.104707. 

[4] Stefaniak, O., Dobrzyńska, M., Drzymała-Czyż, S., & Przysławski, J. (2022). Diet in the prevention of Alzheimer’s disease: Current knowledge and future research requirements. Nutrients, 14(21), 4564. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656789/. 

[5] NIA. (2023, November 20). What Do We Know About Diet and Prevention of Alzheimer’s Disease? National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-and-dementia/what-do-we-know-about-diet-and-prevention-alzheimers-disease. 

[6] Fiorianti, K. (2023, February 27). The MIND Diet for Parkinson’s. Peterson Foundation for Parkinson’s. https://petersonforparkinsons.org/the-mind-diet-for-parkinsons/. 

 

Alzheimer’s Disease In The Brain: A Look Into Insulin Signaling Dysfunction

Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disorder that impairs cognitive functions, specifically memory, making it the leading cause of dementia.[4] Despite not knowing the specific etiology and pathogenesis of AD, the hallmarks are amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs).[1] Recent research has suggested that dysfunctional insulin signaling as well as neuroinflammation accelerate the progression of AD and its associated cognitive decline. Therefore, there is potential in targeting molecules involved in insulin’s signaling pathway including IDE, IRS, PI3K, mTOR, and GSK-3b for future treatment or prevention of AD.

Life 11 01022 g001

Figure 1. Two major hallmarks of Alzheimer’s disease: Aβ plaques and NFTs. [7]

Insulin Signaling – Why is it Important to AD?

Insulin, typically associated with glucose metabolism, has a regulatory role in the brain where it helps promote synaptic plasticity, neurotransmission, and neurogenesis. This is why insulin signaling is important and could be implicated in the progression of AD because when it is functioning properly improves cognitive function.

Insulin Resistance – A Possible Cause of AD?

Insulin resistance happens when the body becomes less responsive to the effects of insulin hormones. This can occur when there are lower levels of insulin binding to its receptors because insulin’s receptors can become desensitized. This can mean that even with insulin hormones being present, they might not bind to their receptors and activate their downstream pathways. Insulin resistance boosts oxidative stress, cytokines production (leading to neuroinflammation), and apoptosis. Insulin resistance leads to Alzheimer’s because it triggers a cascade of disrupted molecules in insulin’s signaling pathways, such as IDE, IRS, PI3K, mTOR, and caspases (Nrf2 and NF-kB).

Fig. 1

Figure 2. Role of the insulin signaling pathway (insulin and its various molecules) in neurodegeneration and Alzheimer’s disease. [5]

Amyloid-Beta to Aβ Plaques

Amyloid-beta peptides are cleaved from the glycoprotein amyloid precursor protein (APP) that plays a major role in neuronal development and signaling. Amyloid-β plaques occur when amyloid-beta proteins clump together outside of the cells. When plaques build up they may block cell-to-cell signaling at synapses or activate an immune response that causes excess cytokines to be released and may be a leading contributor to neuroinflammation in AD cases.

Figure 3. Formation of Amyloid-β plaques from the precursor APP protein. [3]

Tau Proteins to Neurofibrillary Tangles

In healthy neurons, tau proteins help to stabilize and coordinate microtubules, which help give neurons their structure. When insulin signaling is disrupted and PI3K pathways are not being activated properly, Akt does not phosphorylate GSK and inactivate it. When GSK is active it phosphorylates the tau proteins, causing them to break away from the microtubules and clump together into NFTs. Neurofibrillary tangles accumulate inside the cell and block neuron’s normal functioning, including the synaptic communication between neurons. Tau proteins leaving microtubules could also play a role in neurodegeneration because microtubules would not stabilize the cell structure and neuron extensions.

Figure 4. Formation of NFTs from tau hyperphosphorylation. [2]

What Goes Wrong in Insulin Signaling Pathways?

IRS

The insulin receptor substrate relays the signal from the insulin receptor to activate the downstream responses. However, in Alzheimer’s IRS-1 is downregulated, which negatively affects the PI3K pathway. Reduced activation of PI3K/Akt enhances the activation of GSK-3b which increases tau phosphorylation and causes the formation of NFTs.

PTK5/PTPN4-IRS-PI3K-PDK-Akt-FOXO insulin-like signalling pathway in O.... | Download Scientific Diagram

Figure 5. Insulin signaling pathway shown simplified to highlight IRS activation of PI3K pathway. [9]

PI3K and mTOR

Insulin resistance disrupts the PI3K signaling pathway, impacting the activation of mTOR. Since the PI3K pathway activates the mTOR gene to produce nutrients, proteins, and lipids that help other cells grow and create a healthy environment. In AD, with the PI3K pathway not activating mTOR, mTOR can’t produce nutrients to help insulin grow and produce more cells, which creates a bad cycle.

IJMS | Free Full-Text | Targeting PI3K/AKT/mTOR Signaling Pathway as a Radiosensitization in Head and Neck Squamous Cell Carcinomas

Figure 6. PI3K signaling pathway activation of the mTOR pathway involved in cell growth. [8]

IDE

IDE is an enzyme that breaks down insulin and the amyloid-beta protein. In AD, hyperinsulinemia (too much insulin) and insulin resistance affect the activity of IDE, causing insulin to compete with amyloid-beta to bind to the enzyme IDE. When insulin resistance occurs, lower levels of IDE happen because there is a downregulation of the PI3K signaling. Both reduce the clearance and degradation of amyloid-β in the brain, leading to the accumulation of Aβ plaques.

Figure 2. IDE as a pathological link between type 2 diabetes and Alzheimer’s disease. Type 2 diabetes is characterized by hyperinsulinemia and systemic insulin resistance. Insulin is hypothesized to decrease the IDE-mediated beta-amyloid (Aβ) degradation via the competitive inhibition, but this statement needs to be qualified. Insulin also increases Aβ production via other mechanisms, such as increased secretion. The central insulin resistance leads to the reduction of insulin signaling in the brain, which induces the hyperphosphorylation of tau protein and formation of toxic Aβ oligomers by the multiple mechanisms. Particularly, insulin resistance lowers the IDE expression and in this way decreases IDE-mediated Aβ degradation and additionally increases Aβ oligomer levels, which can in turn aggravate insulin resistance in the brain. All these molecular events finally lead to the formation of Aβ plaques and neurofibrillary tangles disturbing the neuronal organization and function.

Figure 7. Insulin decreases the IDE-mediated beta-amyloid (Aβ) degradation through competitive inhibition. Insulin resistance also plays a role as it lowers the IDE expression and decreases IDE-mediated Aβ degradation. [6]

Caspases (NF-kB and Nrf2)

Disrupted insulin signaling (or insulin resistance) activates NF-kB, a proinflammatory transcription factor that releases cytokines and contributes to neuroinflammation, further impacting the progression of AD.

Nrf2 is a regulatory transcription factor that is activated in response to oxidative stress, promoting antioxidation. However, in Alzheimer’s Nrf2 levels are decreased, leading to an increase in insulin resistance and oxidative stress.

 

References

[1] A. A. Abduljawad et al., “Alzheimer’s Disease as a Major Public Health Concern: Role of Dietary Saponins in Mitigating Neurodegenerative Disorders and Their Underlying Mechanisms,” Molecules, vol. 27, no. 20, Art. no. 20, Jan. 2022, doi: 10.3390/molecules27206804.
[2] “Fig. 3. Process of Tau tangle formation during Alzheimer’s diseases…,” ResearchGate. Accessed: Feb. 12, 2024. [Online]. Available: https://www.researchgate.net/figure/Process-of-Tau-tangle-formation-during-Alzheimers-diseases-progressionNFT_fig3_321868408
[3] “Figure 4. A schematic representation of beta-amyloid pathway that leads…,” ResearchGate. Accessed: Feb. 12, 2024. [Online]. Available: https://www.researchgate.net/figure/A-schematic-representation-of-beta-amyloid-pathway-that-leads-to-AD-pathology-The_fig5_312319588
[4] “Home | Alzheimer’s Association,” Alzheimer’s Disease and Dementia. Accessed: Feb. 12, 2024. [Online]. Available: https://alz.org/
[5] A. Akhtar and S. P. Sah, “Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer’s disease,” Neurochemistry International, vol. 135, p. 104707, May 2020, doi: 10.1016/j.neuint.2020.104707.
[6] O. Pivovarova, A. Höhn, T. Grune, A. F. H. Pfeiffer, and N. Rudovich, “Insulin-degrading enzyme: new therapeutic target for diabetes and Alzheimer’s disease?,” Annals of Medicine, vol. 48, no. 8, pp. 614–624, Nov. 2016, doi: 10.1080/07853890.2016.1197416.
[7] P. Prasanna et al., “Microfluidic Platforms to Unravel Mysteries of Alzheimer’s Disease: How Far Have We Come?,” Life, vol. 11, no. 10, Art. no. 10, Oct. 2021, doi: 10.3390/life11101022.
[8] Y.-C. Su, W.-C. Lee, C.-C. Wang, S.-A. Yeh, W.-H. Chen, and P.-J. Chen, “Targeting PI3K/AKT/mTOR Signaling Pathway as a Radiosensitization in Head and Neck Squamous Cell Carcinomas,” International Journal of Molecular Sciences, vol. 23, no. 24, Art. no. 24, Jan. 2022, doi: 10.3390/ijms232415749.
[9] “PTK5/PTPN4-IRS-PI3K-PDK-Akt-FOXO insulin-like signalling pathway in O….,” ResearchGate. Accessed: Feb. 12, 2024. [Online]. Available: https://www.researchgate.net/figure/PTK5-PTPN4-IRS-PI3K-PDK-Akt-FOXO-insulin-like-signalling-pathway-in-O-asiaticus_fig5_330769736

Anything but an ordinary four years

It’s been a tough four years having to learn and make friends during a pandemic. We had one normal semester of our freshman year before being sent home and spending the next two years remote and masked. It’s hard to make new friends and connect with people behind a mask while being distanced. Our senior year was finally our first full normal year and despite the senior slide kicking in, it was worth the wait.

Despite having to take Pchem and neurochem senior year many good things came out of it, such as the group chat “What in the H hat”. I am not going to lie neurochem is not what I expected it to be, and it was hard to connect to the class content. But getting to spend every Monday, Wednesday, and Friday with the neurochem girls was worth it. I expected neurochem to be more lectured based and how chemistry occurs in the brain. However, it ended up being discussion based and how signaling pathways occur in the brain and throughout the body. Learning all of the pathways felt more like biology and being a chemistry major it was a difficult adjustment. These challenges and adjustments are what allowed this class to meet the liberal arts goals established by Concordia.

  1. Instill a love for learning

By having discussion and allowing for us to pick our topics for Wednesday “speed dating” it helped instill a love for learning because we were able to learn more about a specific topic we were interested in and we then got to share this information with each other. The discussions on Fridays were also enjoyable and beneficial to hear other viewpoints and get perspectives from students with varying backgrounds from my own.

  1. Develop foundational skills and transferable intellectual capacities

In this class I was able to make connections to other classes I have taken and understand the interconnectedness of the classes. It also taught me how to communicate science in a way that can be enjoyable to those who are not scientists.

  1. Develop an understanding of disciplinary, interdisciplinary, and intercultural perspective and their connections

By reading a wide range of studies and review posts along with discussing these reading with my classmates I was able to achieve an intercultural  understanding and then by going over the pathways in class helped solidify the disciplinary and interdisciplinary understanding.

  1. Cultivate and examined cultural, ethical, physical, a spiritual self-understanding

Learning about the pathways actually helped explain how various processes occur in the body and why. It allowed for a better understanding of the way things work in the body and why they work that way.

  1. Encourage responsible participation in the world

Neurochemistry definitely encourages participation. By being a discussion-based class and having a dedicated day strictly for discussion of the topic allows for you to become active in discussion and allows you to share your perspective and opinions in a respectful and accepting environment.

By practicing these five goals of liberal learning, not just in neurochemistry but in my last four years at Concordia has prepared me far greater for what is next to come than I could have imagined when I began my freshman year in 2019. A liberal arts education has shown me various classes outside of science that I would have never taken and how everything is interconnected in some way. It was challenging at times to get outside of my comfort zone of science and take an english class or a history class. But having to take these classes along with learn in a pandemic has taught me resilience and determination. That no matter how challenging a time you have you can make it through and when you need help and motivation your professors are right there to encourage you through it too.

The connections I have made with my professors and the chemistry department along with the friendships I have made throughout my last four years are truly something I will never forget and will cherish. I will truly miss the Concordia chemistry faculty and ISC.

Farwell Concordia,

Unlocking Brain’s Potential: Exploring the World of Nootropics

 

Nootropics, also known as cognitive enhancers or smart drugs, are supplements or substances that are believed to improve cognitive function, including memory, creativity, motivation, and focus. Nootropics can be natural or synthetic and work by altering the brain’s neurotransmitter levels, increasing blood flow to the brain, or enhancing brain cell metabolism. Some of the most popular nootropics include caffeine, creatine, omega-3 fatty acids, and certain herbal supplements like ginkgo biloba and bacopa monnieri. While some people swear by the benefits of nootropics, scientific evidence for their effectiveness is limited, and their long-term effects on brain function and health are still not fully understood [1].

 

Cultures and Nootropics

The use of nootropics varies widely across different cultures. In some countries, such as the United States, nootropics are legal and readily available as over-the-counter supplements or prescription drugs. In other countries, such as Taiwan, nootropics are regulated as prescription drugs and are used primarily to treat cognitive disorders such as Alzheimer’s disease [2]. Traditional Chinese medicine has used natural substances, such as ginseng and gingko biloba, for centuries to enhance cognitive function. In India, the traditional practice of Ayurveda uses a variety of herbal remedies, such as ashwagandha and brahmi, to improve cognitive function and reduce stress [3]. Overall, the cultural attitudes towards nootropics vary, and their use and regulation are influenced by factors such as history, politics, and healthcare systems.

 

Fungi as Nootropics

Certain types of fungi, such as lion’s mane (Hericium erinaceus) and cordyceps (Cordyceps sinensis), have been suggested to have nootropic effects. These fungi contain compounds such as hericenones, erinacines, and cordycepin, which have been shown to stimulate nerve growth factor (NGF) and enhance cognitive function. Lion’s mane, in particular, has been shown to improve memory and reduce cognitive impairment in animal studies. Additionally, other fungi such as Reishi (Ganoderma lucidum) and Chaga (Inonotus obliquus) have been traditionally used in herbal medicine for their potential nootropic and health benefits. However, further research is needed to fully understand the effects of fungi as nootropics and their potential risks and side effects [4].

 

Environmental Enrichments During (Animal) Research

Environmental enrichment refers to the provision of stimuli that enhance the physical and social environment of captive animals, promoting species-typical behaviors and improving their welfare. This can include objects, toys, and structures that encourage exploration, play, and social interaction. Environmental enrichment is important because it can reduce stress and improve the mental and physical health of animals, particularly those living in captivity. Examples of environmental enrichment include providing hiding places, puzzles and food-dispensing devices, and opportunities for exercise and social interaction. Enrichment programs are widely used in zoos, aquariums, research institutions, and animal shelters to enhance the well-being of animals in captivity [5].

 

Limitation with Nootropics

Nootropics are challenging to study in neuroscience research due to several reasons. First, many nootropics are classified as dietary supplements and are therefore not regulated by the Food and Drug Administration (FDA), making it difficult to ensure their safety and efficacy. Second, the effects of nootropics on cognitive function are often subtle and subjective, making it challenging to design and interpret clinical trials. Third, there are many different types of nootropics, each with unique mechanisms of action, making it difficult to generalize findings across different substances. Finally, the long-term effects of nootropics on brain function and health are still not fully understood, which further complicates their study [6].

 

Resources

[1] Malík, M., & Tlustoš, P. (2022, August 17). Nootropics as cognitive enhancers: Types, dosage and side effects of smart drugs. Nutrients. Retrieved May 6, 2023, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9415189/

[2] Wu, C.-Y., Hu, H.-Y., Chow, L.-H., Chou, Y.-J., Huang, N., Wang, P.-N., & Li, C.-P. (2015, June 22). The effects of anti-dementia and nootropic treatments on the mortality of patients with dementia: A population-based cohort study in Taiwan. PloS one. Retrieved May 6, 2023, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476616/

[3] Kulkarni, R., Girish, K. J., & Kumar, A. (2012, July). Nootropic herbs (Medhya rasayana) in ayurveda: An update. Pharmacognosy reviews. Retrieved May 6, 2023, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459457/

[4] Tomen, D. (2023, April 10). The nootropic benefits of medicinal mushrooms. Nootropics Expert. Retrieved May 6, 2023, from https://nootropicsexpert.com/the-nootropic-benefits-of-medicinal-mushrooms/

[5] Würbel, & Bayne. (n.d.). The impact of environmental enrichment on the outcome variability and scientific validity of Laboratory Animal Studies. Revue scientifique et technique (International Office of Epizootics). Retrieved May 6, 2023, from https://pubmed.ncbi.nlm.nih.gov/25000800/

[6] Morè, L., Lauterborn, J. C., Papaleo, F., & Brambilla, R. (2020). Enhancing cognition through pharmacological and environmental interventions: Examples from preclinical models of neurodevelopmental disorders. Neuroscience & Biobehavioral Reviews, 110, 28–45. https://doi.org/10.1016/j.neubiorev.2019.02.003

 

The News on Nootropics

What are nootropics

Nootropics are synthetic molecules marketed towards enhancing cognition and increasing focus. There are currently no over the counter nootropics that are FDA approved. Human cognition is a complex and intricate pathway that cannot easily be altered on demand. Therefore, many over the counter nootropics may be acting more as a placebo.

Cognition

The DSM-5 outlines six neurocognitive domains that are linked to an increase in learning and memory which are: perceptual and motor function, language, learning and memory, social cognition, attention, and executive functions.

Perceptual and motor function: visual and visuo-constructional reasoning along with motor coordination.

Language: syntax, grammar, object naming, receptive language, and verbal fluency.

Learning and memory: semantic and episodic memory along with implicit learning. Social cognition: Recognition of individuals emotions and intentions.

Attention: Processing speed and sustained attention.

Executive function: Working memory, planning, decision-making, and flexibility.

These domains do not work independently but rather as an integrated system. Therefore, to effectively enhance cognition a nootropic would have to alter all six pathways.

                Aniracetam

How nootropics work

Nootropics work by positively modulating AMPA receptors and increase neurotrophin levels in the brain.  Ampakines are a class of nootropics that are small molecules the bind and open AMPA receptors to allow for the influx of ions. Ampakines are derived from the nootropic aniracetam. The ampakine binding slows receptor deactivation and desensitization rates. The increased length of the receptor being open allows for a rapid increase in excitatory transmission and ultimately lowers the threshold for long term potentiation (LTP). LTP aids in learning and memory so by lowering this threshold learning can occur at a faster rate. Ampakines can additionally upregulate BDNF expression. Increases in BDNF can surpass the drugs half-life and continue supporting neuronal differentiation and survival. An increase in BDNF can also lead to the increased activation of the Ras-ERK pathway. The Ras-ERK pathway is implicated in establishing long term memories and plasticity. Ampakines can be categorized as either high impact or low impact. High impact ampakines slow the AMPA channels from closing and low impact ampakines accelerates the AMPA channel opening.

Current research

Research thus far has looked at the possibilities of nootropics in proving cognition in older adults and those suffering from Huntington’s and Alzheimer’s disease. The main goal has been to find ways to slow the cognitive decline associated with these diseases. Therefore, researchers recommended young and healthy individuals refrain from taking nootropics since studies have not looked at the effects of nootropics on that age range.

Conclusion

Nootropics or “smart drugs” are thought to enhance cognition and aid an individual in focus and learning. However, human cognition is comprised of six complex and intertwined domains. Therefore, to enhance cognition would be to activate all six domains. Researchers caution against taking over the counter nootropics since they are not FDA approved and have little scientific study of them. Studies that have been done have looked at the nootropic class of ampakines and how they can help older adults’ cognition and those diagnosed with Huntington’s and Alzheimer’s disease.

References

[1] Morè, L., Lauterborn, J. C., Papaleo, F., & Brambilla, R. (2020). Enhancing cognition through pharmacological and environmental interventions: Examples from preclinical models of neurodevelopmental disorders. Neuroscience & Biobehavioral Reviews, 110, 28–45. https://doi.org/10.1016/j.neubiorev.2019.02.003

[2] Brody, Barbara (2022). What are nootropics? WebMD. https://www.webmd.com/vitamins-and-supplements/features/nootropics-smart-drugs-overview

[3] RespireRX (2017). Ampakines development summary. https://www.sec.gov/Archives/edgar/data/849636/000149315217007695/ex99-3.htm

The End to Pain Through Endocannabinoids

What are Endocannabinoids

Endocannabinoids (eCBs) are naturally produced in the body and are lipid-based neurotransmitters. The primary endocannabinoids are arachidonoyl ethionamides (AEA) and 2-archidonoyl glycerol (2-AG) which are agonists to CB1 and CB2 but bind to both receptors. However, CB1 has a higher binding affinity than CB2. eCBs are produced as the body needs them by an increase in intracellular calcium and are degraded through fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). FAAH breaks down AEA and MAGL breaks down 2-AG. The benefits of the endocannabinoid system are that it aids in mood, pain, perception, and learning and memory.

CB1 and CB2 Receptors

CB1 receptors are found primarily in the central nervous system (CNS) and CB2 receptors are primarily in the peripheral nervous system (PNS). CB1 receptor accounts for being the most abundant GPCR in the CNS but is also located on peripheral nerve terminals. Besides binding AEA and 2-AG THC, the main ingredient in cannabis sativa (marijuana), binds at CB1. CB2 receptors can be found in the CNS but are mainly located in cells and tissues of the immune system. CB2 receptors in the CNS are localized to microglia and modulate inhibitory plasticity. Additionally, CB1 and CB2 receptors operate independently from each other.

Receptor Activation

Following activation of CB1 there is a rapid decrease in the levels of cAMP via adenylate cyclase inhibition. This decrease occurs through activation resulting in potassium channel conductance and a decrease in calcium voltage operated channels. Ultimately resulting in a decrease in neurotransmitter release. However, prolonged exposure can result in tolerance and a decrease in the ability of the receptors to activate the endocannabinoid pathway. AEA and 2-AG can bind and activate CB receptors but so can THC and CBD from marijuana.

AEA, 2-AG, THC, and CBD are the only agonists that can bind to CB receptors. However, there are ways to enhance endocannabinoid levels and receptor activation. Both dark chocolate and black truffles contain anandamide (naturally produced endocannabinoid), caffeine, olive oil, exercise, and omega-3 fatty acids upregulate CB receptors. Lastly, cold exposure increases endocannabinoid levels and flavonoids found in tea and wine inhibit the breakdown of endocannabinoids.

Endocannabinoids and Pain

The activation of the endocannabinoid system is associated with pain reduction. However, natural endocannabinoids may not be able to provide the level of activation required of the endocannabinoid system which is when cannabinoids of THC and CBD are introduced. Research has linked cannabis to control and manage pain associated with Alzheimer’s disease (AD), Huntington’s disease (HD), and multiple sclerosis (MS). In MS eCB system activation reduced pain and spasms and provided neuroprotective and anti-inflammatory effects. In HD CB1 receptor activation is reduced, resulting in reduced motor performance. Therefore, enhanced activation of remaining CB1 receptors may help the degradation of the receptors. In AD CB receptor activation is thought to produce a neuroprotective effect and protect individuals against amyloid beta plaque toxicity and reduced tau phosphorylation.

Conclusion

Endocannabinoids are naturally produced in the body and are agonist to CB1 and CB2 receptors, as are phytocannabinoids, THC and CBD. The activation of the endocannabinoid system has been linked to pain reduction, mood stabilization, and memory and learning. Research has begun investigating the therapeutic effects of endocannabinoids on diseases such as HD, MS, and AD.

References

[1] Kendall, D. A., & Yudowski, G. A. (2017). Cannabinoid receptors in the central nervous system: Their signaling and roles in disease. Frontiers in Cellular Neuroscience10. https://doi.org/10.3389/fncel.2016.00294

[2] De Pietro, MaryAnn, CRT (2021). What to know about endocannabinoids and the endocannabinoid system. Medical News Today. https://www.medicalnewstoday.com/articles/endocannabinoid

[3] Fallis, Jordan (2023). 26 powerful ways to boost your endocannabinoid system. Optimal Living Dynamics. https://www.optimallivingdynamics.com/blog/how-to-stimulate-and-support-your-endocannabinoid-system#:~:text=Medium%20and%20high%2Dintensity%20exercise,68%2C%2072%2C%2074)

Final Blog

Introduction

I enjoyed this class because it gave me a chance to blend what I learned from my neuroscience classes with what I learned from my psychology classes. This class focused on the pathology of mental disorders, but I found that my psychology background helped me better understand the whole picture. Both aspects are important because the biology of the brain determines the behavior, but your behavior can also affect the biology of the brain, and both need to be addressed when treating mental disorders. My understanding of mental disorders helped me to connect more with the pathology behind them.

I also think that my psychology background gave me a unique perspective on some of the topics that we covered during our Friday discussion days. I think it’s really easy for the sciences to forget about the humans behind the disorders that are being studied. While psychology is not immune to this, I think neuroscience is at a greater risk because it is so focused on pathology and often only used animal models in its research. The fact that I was taking Abnormal Psychology at the same time as this class made me a lot more aware of how I talk about mental disorders, like when we discussed depression and psychopathy, and how these discussions weren’t always the most sensitive. I know I had to work really hard to keep my comments both scientifically accurate and empathetic at the same time and my psychology background helped me with this.

 

What Kinds of Learning Occurred for You During this Semester?

My learning for this semester wasn’t so much focused on memorizing information as it was on learning how to read scientific publications and present my findings. Yes, I learned about a lot of signaling pathways that I was unfamiliar with, and I am at least generally aware of how they work now. But there was a lot more time spent on practicing how to read scientific articles, because they’re not the type of writing that you can just pick up, read once, and expect to understand what is going on. You have to take notes, you have to highlight the important parts, you have to identify what you don’t understand and then research those parts. I think that was the most important skill that I learned. The importance of figuring out what you don’t understand and then learning how to teach yourself about it. This was something that I had never done before because I assumed I was supposed to understand everything on the first try. I’m glad that I learned this skill though because it made the publications a lot easier to understand and a lot more enjoyable by proxy.

If You Were to Highlight on Your Resume a Skill or Competency that You Improved this Semester, What Would You be Sure to Include?

This class will be very useful for my future career plans of going into research. The focus that this class placed on understanding how to read scientific articles will come in handy since a lot of research is reviewing past literature. I also found the focus on communicating our findings to the general public to be very useful. When you’re taking a lot of STEM classes and you are friends with mostly other STEM majors, it can be really easy to forget that not everyone understands the lingo that you use. I found the weekly blog posts to be a useful exercise to help me get out of the habit of using those complicated words, because every time I used a niche word, I had to explain what it meant and that got tedious. These blog posts also helped me think more about the way that I present information. Is it entertaining? Is it easy to follow? Am I putting people to sleep with this long paragraph? These are all questions that I started to ask myself when writing my blog posts, and I am hoping to carry that habit with me when writing my own scientific articles.

I’m really glad that this class focused so much on becoming better writers. It’s something that is often overlooked during our science classes, which explains why research articles can be so difficult to read. Hopefully I can be one of the good writers in the scientific community and people will actually like reading my publications.

Conclusion

This class was both really challenging but also fun. The homework took a really long time, but I feel the skills that I gained from doing the homework made it worth the time. It wasn’t just busy work, it taught me how to read and understand scientific articles. It also taught me how to share research with the general public in a more digestible manner. This is a skill that more science students need to be taught because currently academic writing in the sciences is atrocious. I think these skills will be extremely valuable to me when I graduate because I’m planning on going into research, and that field requires a lot of reading scientific literature and sharing my findings with the public. I’ll be sure to put this class on my CV to highlight the skills that I gained.

 

A Journey.

Concordia and me

In high school, I never thought I would pick Concordia College for the next four years of my education. It was really the people here that drew me into picking the school. I remember visiting schools across the nation and thinking I do not want to stay this close to home, so I don’t need to look at Concordia. I don’t know how or why I did look into Concordia, but the community caught my attention. I got the opportunity to talk to a professor and it really struck me that those small classrooms, close connections to my professor and peers are what I wanted. Throughout my years here now, I have really seen myself learn and grow through not only the curriculum, but also the community within the science department and outside of it too.

Concordia has five goals set in place for the liberal learning experience here on campus. The first is to instill a love for learning. There were definitely classes that I thought were brutal and I won’t lie, it was stressful keeping up sometimes. At the end of the day, however, I was always beyond impressed by how much I found myself learning about so many different topics. Neuroscience was just a major that I thought would be fun to learn about, but I can say all my neuroscience classes were by far my most favorite and I loved learning in every single one of them. I ended up adding a Biology major because why not learn more in more areas!?

The second goal is to develop foundational skills and transferable intellectual capacities. All of my classes have always been so hands on and discussion based where I feel like I gained skills that would be applicable to real life. The labs especially taught me a large varieties of skills including teamwork, problem solving, scientific reasoning, etc. My environmental and global studies classes were also important I thought to me because they gave me more knowledge of real world issues that I otherwise may have been ignorant about.

The third goal to develop an understanding of disciplinary, interdisciplinary, and intercultural perspectives and their connections. While I love my major specific classes, I really liked the well rounded aspect of the liberal learning here at Concordia that allows me to take classes of different subjects as well. I feel like I know so much more about the world and everything out there. My Spanish and inquiry classes especially we got to go out in the communities and talk to people and that was very cool! In my inquiry, we got to go to the New American Consortium and work with people of different cultural backgrounds, which was one of my favorite experiences right off the bat coming into college. These experiences in such classes I thought also really pushed for the fifth goal which is to encourage responsible participation in the world. The clubs and activities also added to my growth in these areas, especially when I was on the DEIC executive committee board. That role was especially fun because I got to really learn about different culture’s celebrations in order to recreate them here on campus. I think this also helped with the fourth goal: Cultivate an examined cultural, ethical, physical and spiritual self-understanding. I think I learned more about myself and the diverse group of people around me through my experiences at Concordia.

This semester and me

This semester was one of my favorites because I think I learned about so many diverse subjects in my classes. Neurochemistry was one of my favorites in my entire college career because of the design of the class being so discussion heavy. In this class I felt like I could use prior knowledge from many of my classes to analyze real life health conditions affecting people in the world. Once we problem solved understanding research articles and the brain pathways causing a variety of illnesses, we could dig deeper into the subject. It was not always just straight science. The open ideas structure really allowed us to learn about so much more like environmental impacts on health or psychological or food or the government and societal stigma. The topics were endless and I loved that lack of restriction in class.

The amount of information and just analyzing skills I have gained from reading, understanding, and discussing so many articles will for sure help me in my career path to becoming a doctor. I think any career, including the ones in healthcare, need skills that involve investigating what is wrong and how it can be fixed. We did this a lot with so many different health conditions throughout the semester. Knowing how these health conditions are formed was really interesting and will be impactful in the future when I may have patients who have many of these.

The discussion-based format of Neurochemistry also played such a huge role in the friendships I have strengthened after the class. Instead of just sitting next to strangers for a semester and listening to lectures, we got to talk to each other and hear so many perspectives of people with so many different backgrounds. We even started hanging out outside of class, which we had never done before this class (as seen in the top featured picture).

 

 

Neurochemistry End of Semester Reflection

Neurochemistry allowed me to integrate and apply the skills and competencies gained throughout the intersectionality of liberal education learning at Concordia in few ways:


Critical thinking

Liberal education emphasizes critical thinking and analysis. Neurochemistry required us to analyze complex information, synthesize information from multiple sources, and evaluate evidence. By applying critical thinking skills to this subject, we as students can strengthen our ability to analyze and evaluate complex issues in other areas.


Interdisciplinary learning

Neurochemistry draws on knowledge from various fields, including biology, chemistry, neuroscience, and psychology. As such, we can integrate and apply our learning from these different disciplines. This interdisciplinary approach is a hallmark of liberal education, and we can take these skills we gained throughout the semester learning and analyzing neurochemistry through different signaling pathways and social and environmental factors with us as we pursue other areas of study or work.


Effective communication

Liberal education places a strong emphasis on effective communication. Throughout the semester we needed to be able to communicate complex concepts and ideas to our classmates. By practicing effective communication skills in this context, we can enhance our ability to communicate effectively in other areas, such as in written assignments, presentations, or group discussions.


Ethical considerations

Neurochemistry has significant implications for society, including in the areas of healthcare, law, and public policy. A course in neurochemistry can allow us to explore ethical considerations related to these areas, including issues related to consent, confidentiality, and privacy. By considering these ethical questions, students can develop a deeper understanding of the importance of ethical decision-making in all areas of life.

In summary, neurochemistry allowed me to integrate and apply the skills and competencies gained throughout liberal education learning by providing opportunities for critical thinking, interdisciplinary learning, effective communication, and consideration of ethical implications that I will continue using in my future plans (wilderness therapy) and when interacting with human beings.

I was challenged and supported through this course that had a very refreshing structure. Neurochemistry was a discussion based class that involved cooperative learning, problem solving, and understanding different cultures and their approach to neurodegenerative disorders. It was so exciting to learn from students from different majors than just neuroscience. I gained insight from chemistry, biology, psychology, environmental studies, and dietetics. We all focus on our strengths and we were still willing to learn about different disciplines and work experiences.

My favorite part of this semester was experiencing how all four of my courses were intertwined. I was able to apply my knowledge and see the intersectionality from my Neurochemistry, Intercultural Communication, Religion, and Philosophy of Disability class. There was a lot of tension between these courses that gave me a deeper understanding of the problem of ableism, and the ways in which philosophical investigation could enhance the lives of individuals with disabilities and the fairness of institutions ranging from politics to the medical field. My liberal arts education is making me a more empathetic and aware being. I would love to see courses like philosophy of disability to be required courses for individuals that are planning on going to the medical field. These humanities courses would give insight and compassion to how diverse human experiences effect our systems and personal lives in this world structured for white, cis, able bodied individuals.

Cognitive Impairments and Nootropics

Artstract by Dhruvika Patel

What are Cognitive Impairments?

Cognitive impairments are issues that interfere with a person’s ability to think, learn, remember, use proper judgement, and make thought out decisions. There are many signs that can be found in those that might have an impairment, including memory loss, difficulty with concentration, task completion, remembering, following instructions, and solving issues. Due to the wide variety of impacts that can occur, it makes sense that there would be detrimental effects not only on the person, but also their family’s finances. These finances can be a result of increased costs for education, healthcare, and personal daily care. Furthermore, we can’t ignore the emotional burden that also falls upon the family to take on an often-lifelong responsibility. However, their story is not destined to be hopeless forever. There are therapies that can occur to better cognitive abilities along with further research that looks at more possibilities to train the brain through enrichments.

Epigenetics and Enrichment

Epigenetic mechanisms regulate transcription and gene expression. Recent findings suggest that epigenetic processes can be changed through environmental and social rearing conditions. An epigenetic modification is BDNF increase in the hippocampus exposed to environmental enrichment. Environmental enrichment is comprised of 3 domains: increased physical activity, increased social groupings, and increased opportunities for exploration. There are complications to enrichment studies; however, these include having a control group with no confounding variables and manipulating the genome in mutant mouse models.

Brain Mechanisms

Fig 2. This figure represents how one’s lifestyle and environment works with BDNF production. (1)

Cognitive function depends mainly on neuronal activity and engagement of synaptic proteins and signaling cascades to promote the establishment and strengthening of synaptic contacts. Positive modulators of AMPA receptor have positive effects on learning and memory in rodents. Ampakines are a class of positive allosteric AMPA receptor modulators that work with learning and memory but also promote BDNF expression and protect the brain from neurodegeneration. BDNF is important for neuronal survival, differentiation in the brain, and LTP and learning. Furthermore, Ras-ERK signaling activation is needed for LTP and long-term memories, so germline mutations can be responsible for a variety of neurodevelopmental disorders. BDNF is one thing that is engaged in this RAS-ERK pathway and is important in LTP.

BDNF

Brain-derived neurotrophic factor is like the fertilizer of the brain. It is found in the CNS, gut, and other tissues that play an important role in neuronal survival and growth, is a NT modulator, and helps with neuronal plasticity, which is important for learning and memory. BDNF is synthesized in the brain and is released in response to neuronal activity. It binds to specific receptors on the surface of neurons, promoting their survival and growth. Therefore, sufficient BDNF is very important in cognitive abilities. Reduced levels of BDNF are associated with impaired cognitive function and increased risk of cognitive decline and neurodegenerative diseases. Conversely, increased levels of BDNF have been linked to improved cognitive function and better outcomes in conditions such as Alzheimer’s disease and depression. Several studies have suggested that certain nootropics, such as caffeine, creatine, and omega-3 fatty acids, may increase BDNF levels in the brain.

Fig 2. This figure illustrates the effects of BDNF on pathways. (2)

Conclusion

Cognitive impairments impact a fairly large number of people in the world; it not only affects the person, but also their family. BDNF is one area that has been looked at due to its connection with neuronal plasticity. There are natural nootropics that can be taken to enhance such brain function along with environmental enrichment.

Citations

Faiz, M. (2022, February 11). What is BDNF and Why it’s Important for Mental Health? Personalized Prescribing. https://personalizedprescribing.com/blogs/news/what-is-bdnf-and-why-its-important-for-mental-health

Jin, Y., Sun, L. H., Yang, W., Cui, R. J., & Xu, S. B. (n.d.). The role of BDNF in the neuroimmune axis regulation of mood disorders. Frontiers in Neurology, 10. https://doi.org/10.3389/fneur.2019.00515

Morè, L., Lauterborn, J. C., Papaleo, F., & Brambilla, R. (2020). Enhancing cognition through pharmacological and environmental interventions: Examples from preclinical models of neurodevelopmental disorders. Neuroscience & Biobehavioral Reviews, 110, 28–45. https://doi.org/10.1016/j.neubiorev.2019.02.003

NCI dictionary of cancer terms. (n.d.). National Cancer Institute. Retrieved May 4, 2023, from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/cognitive-impairment

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