The Truth About Psychopathy and Stereotypes!

Artstract by Olivia Pederson

What is Psychopathy? 

Psychopathy is a personality disorder and is characterized by persistent antisocial behavior, impaired empathy and lack of remorse. Psychopathy is also grouped with antisocial personality disorder (ASPD) which is characterized by aggression, hostility, callousness, manipulativeness, deceitfulness, and impulsivity. Psychopathy is a severe manifestation of ASPD.

ASPD affects 1-3% of the general population and affects 40-70% of prison populations.

Psychopathy affects 1% of the general population and affects 10-30% of prison populations.

 

How Does it Get Diagnosed?

Psychopathy is not listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) because it is underfunded and under treated. Another reason is that in the past, people who studied psychopathy were worried about the stigmatization that would come with a label such as ‘psychopath’ whereas other clinicians were worried about the ability to asses the traits associated with psychopathy (callousness, cruelty). Psychopathy was replaced with ASPD, which focuses more on the behavioral aspects of psychopathy. Because of this grouping, only about 1/3 of of those diagnosed with ASPD also fit the criteria for psychopathy.

According the the graph above, this type of disorder can be seen in all ages. For younger people, the closest diagnosis is called conduct disorder, which manifests itself as lack of guilt, lack of remorse, callous lack of empathy, lack of concern for oneself, and a general lack of emotional expression.

When diagnosing psychopathy, a questionnaire called the Psychopathy Checklist Revised (PCLR). This is a 20 item scale that is scored from interview and file information. This questionnaire tests two different factors:

  1. Factor 1: Emotional Detachment
    • superficial charm, manipulativeness, shallow affect, lack of guilt and lack of empathy
  2. Factor 2: Antisocial Behavior
    • deviance from an early age, aggression, impulsivity, irresponsibility, process to boredom

This questionnaire will lead to a score and then placed on a scale and compared to ‘normal’ ranges.

What Drives Psychopathy? 

Researchers do not know much about the true cause of psychopathy and ASPD. Previous research has shown that there may be some brain abnormalities involved with the symptoms of psychopathy and ASPD. In this research, the amygdala (an important structure for emotional-processing) was smaller in people with the symptoms associated with these disorders.

In other studies, it has showed that there are genes involved with these disorders. Research like this has not really been done before so it is astonishing to make this connection between genes and personality disorders. Genes such as ZNF132 and RPL10P9 were shown to be abnormal in those with ASPD/psychopathy. These genes were unable to make the correct amount of protein for the cells, which lead to insulin activity and glucose metabolism.

Another connection found in this research is the fact that there were changes in the opioid system, which supports prosocial functions (empathy). The opioid system is deficient which contributes to ASPD, which could mean that antisocial individuals attempt to stimulate their opioid system by the rewarding effect they get from impulsive and aggressive behavior.

Stereotypes? 

There are many stereotypes when it comes to the term psychopath. Most of these stereotypes come from media. Most notably, Joe Goldberg from the hit TV show You and Norman Bates from the hit TV show Bates Motel. The TV and movie industry has made a lot of money off of dramatizing people and the term psychopath, but these are not an accurate depiction of what it is like to live with the psychopath label (Norman and Norma Bates on the left and Joe Goldberg below).

Being labeled a psychopath, or a sociopath, or even as someone with ASPD can be debilitating. While there is some forms of treatment to try and help people change their thought patterns and their behaviors, this label will forever be with them. Not everyone with this label is a cold-blooded, evil monster. These people are human beings just like you that don’t get to choose whether their genes code for this major lack of empathy.

So the next time you grab a bowl of popcorn and throw on a mystery/thriller movie with a psychopath killer, try to remember that not everyone labeled a psychopath is going to be a murderer.

 

 

References:

pubmed.ncbi.nlm.nih.gov/31455857

apa.org/…or/2022/03/ce-corner-psychopathy

arc.psych.wisc.edu/…/psychopathy-checklist-revised-pclr

Untangling the Mysteries of Sleep: A Neuroscience Perspective

Artstract #2

Sleep is a complex and multifaceted phenomenon that remains a challenging subject for scientific research. One of the major challenges of studying sleep is that it is a subjective experience, making it difficult to objectively measure and quantify. Another challenge is the variability in individual sleep patterns, making it challenging to generalize findings across different populations. Additionally, sleep is influenced by a variety of factors such as genetics, environmental factors, and lifestyle habits, which makes it challenging to isolate specific variables for study. Furthermore, studying sleep often requires invasive and costly techniques, such as electroencephalography (EEG) and polysomnography (PSG), making it difficult to conduct large-scale studies [1].


Sleep Stages [2]

Sleep stages are categorized into four distinct phases: NREM 1, NREM 2, NREM 3, and REM sleep (Figure 1). NREM 1 is the lightest stage of sleep and is characterized by a reduction in muscle tone. NREM 2 is deeper, while NREM 3 is the deepest stage of sleep. REM sleep is associated with vivid dreams and rapid eye movement. Sleep cycles through these stages several times throughout the night, with REM sleep occurring more frequently towards the morning. Each stage plays a crucial role in the restorative and regenerative functions of sleep, affecting physical and mental health.

Figure 1. Stages of Sleep

cAMP/MAPK/CRE transcriptional pathways [3]

The cAMP/MAPK/CRE transcriptional pathways play a crucial role in the regulation of sleep and memory processes in the brain. These pathways are involved in the activation of gene expression and protein synthesis, which are necessary for the consolidation of long-term memories and the regulation of sleep-wake cycles.

Studies have shown that the activation of the cAMP/MAPK/CRE pathways can promote wakefulness and decrease the amount of sleep, while inhibition of these pathways can increase sleep duration. In addition, these pathways have been implicated in the formation and retrieval of memory, as they are involved in the regulation of synaptic plasticity and neuronal connectivity (Figure 2).

Overall, the cAMP/MAPK/CRE pathways provide a molecular framework for the regulation of sleep and memory processes in the brain, and understanding their mechanisms may lead to the development of novel therapeutic approaches for sleep and memory-related disorders.

Figure 2. It is suggested that upstream cAMP stimulation of Ras and/or Rap1 in conjunction with PKA suppression of STEP phosphatase causes MAPK activation during exercise. The eventual reduction in pMAPK could be brought on by STEP’s calcineurin reactivation. It is proposed that the CaM-stimulated adenylyl cyclases are necessary for the durability of hippocampus-dependent memory, and that memory is preserved by a diurnal oscillation of this route in the hippocampus. It is believed that the cAMP/MAPK/CREB transcriptional pathway reaches its peak activity in REM sleep, specifically during the light phase of the circadian cycle.


Environmental Factors [4]

Sleep is significantly influenced by various environmental factors, including light exposure, temperature, noise, and air quality. Exposure to bright light in the morning can promote wakefulness and reset the circadian rhythm, while exposure to light at night can disrupt sleep and suppress the production of melatonin, a hormone that regulates sleep-wake cycles.

Temperature also plays a crucial role in sleep, as a cool environment can promote sleep onset and quality, while a warm environment can interfere with sleep (Figure 3). Noise and air quality can also disrupt sleep by causing arousal and respiratory disturbances.

Other environmental factors, such as stress, physical activity, and diet, can also affect sleep. Understanding and managing these environmental factors is crucial for promoting healthy sleep and preventing sleep-related disorders.

Figure 3. Duration of sleep and GDP of countries across different climate zones (temperature, air quality, noice) and resources


Sleep-Related Disorders [5]

Sleep-related disorders are a group of conditions that affect the quality, timing, and duration of sleep. These disorders can range from mild to severe and can significantly impact overall health, quality of life, and daily functioning.

Some of the most common sleep-related disorders include insomnia, sleep apnea, restless leg syndrome, and narcolepsy. Insomnia is characterized by difficulty falling asleep or staying asleep, while sleep apnea is marked by interrupted breathing during sleep. Restless leg syndrome is characterized by an irresistible urge to move the legs during rest, while narcolepsy is a neurological disorder that causes excessive daytime sleepiness and sudden sleep attacks.

Effective diagnosis and treatment of sleep-related disorders can significantly improve sleep quality, reduce daytime fatigue, and enhance overall health and well-being.

Conclusion

Sleep is a complex and multifaceted phenomenon that remains a challenging subject for scientific research. Sleep is influenced by a variety of factors such as genetics, environmental factors, and lifestyle habits, which makes it challenging to isolate specific variables for study. Therefore, some individuals are more fortunate to have better quality sleep than others based on their living resources and location.

Resources

[1] How sleep works: Understanding the science of sleep. Sleep Foundation. (2022, October 19). Retrieved March 29, 2023, from https://www.sleepfoundation.org/how-sleep-works

[2] Stages of sleep: What happens in a sleep cycle. Sleep Foundation. (2023, March 2). Retrieved March 29, 2023, from https://www.sleepfoundation.org/stages-of-sleep

[3] Xia, Z., & Storm, D. (2017). Role of circadian rhythm and REM sleep for memory consolidation. Neuroscience Research118, 13–20. https://doi.org/10.1016/j.neures.2017.04.011

[4] Environmental sleep factors |. | World Sleep Day March 17, 2023. (2015, September 16). Retrieved March 29, 2023, from https://worldsleepday.org/environmental-sleep-factors

[5] Centers for Disease Control and Prevention. (2022, December 14). Key sleep disorders – sleep and sleep disorders. Centers for Disease Control and Prevention. Retrieved March 29, 2023, from https://www.cdc.gov/sleep/about_sleep/key_disorders.html

Can You Learn In Your Sleep?

What really is sleep?

We all know what sleep is and what it looks like, but what goes on in the brain during sleep? You may have heard that it’s good for you; that it helps heal your brain. But how does it do this? What are dreams? You may have also heard that sleeping helps improve you memory, how does that work?

Phases

Sleeping is a repetitive cycle of varying brain activity. In a typical night the average person will go through 4-6 of these cycles.

  • Stage 1: NREM (non-rapid eye movement) 1, this stage typically lasts 1-7 minutes and is really just the beginning of when you fall asleep. The body is not fully relaxed, but brain and body activities start to decrease.
  • Stage2: NREM2, this typically lasts 10-25 minutes during the first cycle. The body drop sin temperature, and breathing and heart rate will slow down. Brain activity also starts to decrease.
  • Stage 3: NREM3, this is known as deep sleep or slow-wave sleep. Muscle tone, breathing, and heart rate decrease greatly in this stage. Brain activity takes on large, and ‘slow-moving’ waves known as delta waves.
  • Stage 4: REM (rapid eye movement). Brain activity during this stage mimics activity while awake, and muscle paralysis will set in. Even though the eyes remain closed they are moving quickly

REM Sleep

Schematic depicting the physiological changes that occur during REM sleep

REM sleep is often regarded as the stage where a lot of the benefits of sleep occur. EEG analysis shows that memory consolidation pathways are activated during REM sleep. The more you learn throughout the day increased the amount of REM sleep during that night, indicating that REM sleep is important for learning and memory formation. You can read more about sleep cycles and REM here.

Pull an All-Nighter or Sleep?

Image showing memory formation corresponding to daylight cycles. Notice how consolidation aligns with night and sleep.

Given the research showing that REM sleep can help consolidate memories, is it better to spend more time studying? Or is it better to study what you need then sleep on it? A lot of benefit can come from sleeping rather that studying all night long.

 

References

  1. Stages of sleep: What happens in a sleep cycle. Sleep Foundation. (2023, March 2). Retrieved March 29, 2023

  2. ScienceDaily. (2020, June 5). Memory consolidation during REM sleep. ScienceDaily. Retrieved March 29, 2023

Sleeping May Replace Studying — Every College Students Dream Come True (Literally)

Since elementary school, I recall being told to get a “good night’s sleep” before tests – I, along with many other kids, did not take this seriously. In college, I finally discovered the importance of sleep, especially in organic chemistry when every night I was dreaming about SN2 and Grignard reaction mechanisms, waking up to a greater understanding and solidification of these concepts. Too often, I hear my fellow students talking about studying all night before exams as if it is going to help them – it does not! It is actually detrimental to their exam performance. Studies have found that fewer than 10% of college students sleep the recommended 7-8 hours at night during finals. How detrimental is this really? What does the lack of sleep really do? It has been shown that sleep, particularly REM sleep, is crucial for memory consolidation and long term memory formation. 

Sleep

The sleep cycle is broken into NREM (non-rapid eye movement) and REM (rapid eye movement) sleep. NREM sleep consists of three stages in which the body repairs tissues and strengthens the immune system. REM sleep happens about 90 minutes after falling asleep and is important in the stimulation of the regions of the brain important for learning and protein production. REM sleep brain activity waves are comparable to waves seen during wakefulness and alertness. The stages of NREM and REM sleep are depicted below. 

Hormones and Clock Proteins

Melatonin and cortisol are the primary circadian hormones and they are both produced in the pineal gland and released according to lightness or darkness. The retina at the back of the eye has photoreceptors called rods and cones that respond to light and darkness, and they have signaling attachments to the optic nerve which connects to the pineal gland. With darkness, melatonin is released and from the morning light, cortisol is released to wake us up. Melatonin increases the expression of the clock protein, PER1. This protein is of the period gene which encodes circadian rhythms of locomotion, metabolism, and behavior. Since melatonin increases this expression, it is concluded that PER1 plays the largest role in our decreased locomotion and metabolic rate in our sleep. 

Memory Consolidation and Sleep

It has long been proposed that memories are consolidated in our sleep by, for example, dreaming of our awake experiences (like organic chemistry). However, the biological reasoning was lacking – until now! It has been found that the cAMP/MAPK/CRE-mediated transcription pathway, a key memory consolidation pathway, reaches a maximum during REM sleep. In individuals with dysfunction of this pathway, perhaps a sleep deprived individual, long term memory formation is blocked. In order for memories to be consolidated, there must be repeated reactivation of these signals to maintain required protein levels for persistence of these memories. This repetition actually occurs in our sleep! The suprachiasmatic nucleus is the “circadian pacemaker” of the brain, and it also controls the oscillation of cAMP, MAPK, and CREB levels. It has been found that this oscillation reaches maximum activity of these pathways during REM sleep! 

In summary, during REM sleep a crucial memory consolidation and neuroplasticity pathway is at its highest activity, consolidating awake moments into long term memories. So, sleep the night before exams! If you study during the day, these concepts will replay during REM sleep and turn into a long term memory, maybe even making more sense when you wake up!

References

  1. Ryan, T. (2022). A Study Guide To Getting Sleep During Final Exams. Sleep Foundation. Retrieved March 22, 2023, from https://www.sleepfoundation.org/school-and-sleep/final-exams-and-sleep#:~:text=If%20school%20and%20sleep%20don,Fewer%20than%2010%25 
  2. What are REM and Non-REM Sleep? WebMD. Retrieved March 22, 2023, from https://www.webmd.com/sleep-disorders/sleep-101
  3. Anderson, L. (2019). Melatonin and Cortisol. Thriven Functional Medicine Clinic. Retrieved March 22, 2023, from https://thrivenfunctionalmedicine.com/melatonin-and-cortisol/#:~:text=Melatonin%20works%20to%20keep%20circadian,which%20is%20our%20awake%20hormone.
  4. PER1 Gene – Gene Cards. Retrieved March 22, 2023, from https://www.genecards.org/cgi-bin/carddisp.pl?gene=PER1
  5. Xia, Z.; Storm, D. (2017). Role of circadian Rhythm and REM sleep for memory consolidation. Neuroscience Research 118, 13-20. https://doi.org/10.1016/j.neures.2017.04.011

Emotional Memories and Sleep

 

https://inkshed.web.unc.edu/2020/07/just-sleep-on-it/

Sleep, is potentially one of the most important things in our lives. According to John Hopkins’ website we spend around a quarter to a third of our life sleeping. If you’re a person like me, who wishes there was more hours in the day. It seems like a lot of time wasted or that could be used else where. With 8 hours being the recommendation obviously it must be important that we do get proper sleep. Yet, what is really happening during this time that makes it more valuable than staying up?

Sleep plays a role in neural plasticity, rest of the body, circadian rhythm, memory, and so much more.  I like to think the sleep is like writing a summary of your day but in your brain. It is the time where everything is devoted to recapping, resetting, and segmenting for a new day. Of the many factors can disrupt sleep. Things like physical comfort, uneasiness, diet etc. can all disrupt sleep. Emotional memory and emotional state can alter sleep and can be altered by sleep.

What is emotional memory?

Emotional memory is our ability to consciously remember our experiences. Every emotional event that happens to us needs to be encoded into our memory during our sleep. In a 2011 article on Emotional memory processing talked about an “affective tone” theory. That each night our brain needs time to process the “tone” of how this event occurred. Meaning our brain tries to make sense of the event. If it was negative, positive, what did we learn from it. The more complex it is to understand the longer it takes our brain to break it down and store it properly. It can take multiple nights, but once our brain concludes the core memory is finally stored. This also leads to the reasoning why major events get stored in long term memory or short.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182440/

How does sleep effect our memories?

A study tested the storing and recall of positive negative and neutral memories, or in the study they used pictures instead of memories. They found that positive images had a better recall compared to negative. They also had participants go through a fMRI which showed that when thinking of the positive memories they were stored during REM (rapid eye movement) sleep. The negative images were stored in SWS (slow wave sleep). During REM sleep the brain moves memories from short term to long term memory. The adrenergic system in the brain is used during SWS as the brain leaves REM sleep. Memories that are more stimulating are easier to recall. These memories also make the adrenergic system to work more.

https://academic.oup.com/cercor/article/25/6/1565/300470?login=false

Why is sleep important?

Lack of sleep, or sleep deprivation lowers the function of temporal memory. Temporal memory is often referred to as out short-term memory. If the structures responsible for short term memory storage is thrown off due to lack of sleep. It can cause a change in the normal cascade of all memory storage. If memories aren’t stored in the short term. How can they be properly stored in our long-term memory. Lack of sleep can also throw off each night’s sleep cycle through the different stages of sleep. This means since different brain functions during sleep are dependent on each sleep cycle. Lack of sleep doesn’t allow to brain to decompress how it properly needs to.

Environmental Impact on Memory Consolidation during Sleep

What is memory consolidation?

In the most simplest terms, memory consolidation is the process of converting a short term memory into a more stable, long-term memory. Memory formation typically occurs in three different stages: encoding, storage, and retrieval. Encoding is the sensory inputs that have to be transformed into storable memory inputs. Storage then is how that encoded information is then transferred to the sense organs and retained. Finally, retrieval is how one can get access to the actual memory stores in the brain when wanting to recover information. The biology of how conscious memory is stored is that it is dependent on storage in the hippocampus and neocortex. The information is first stored in the hippocampus, known for its fast-learning system. Next, it is trained in the slow learning system of the neocortex. Memory consolidation is strengthened through this process by potentiation-a process requiring conduction of information from neuron to neuron to create a strong synaptic workforce. The more signals that pass through the synapse from one to neuron to the next, the more potentiation is built.

This is the simplest diagram of how memory consolidation works. Consolidation is the transfer of memory from short term to long term, which can be strengthened through rehearsal. (1)

However, how does sleep play a role in this potentiation? REM sleep. That is the key stage of sleep that seems to have the greatest impact in strengthening potentiation. REM sleep is known as active sleep, which elicits neuronal activity in the brain through neuronal plasticity. The promotion of neuronal activity during REM sleep can therefore help consolidate memories and information a person stored during the day.1

An illustration of how memory from the day is consolidated during sleep for best retrieval the next day. (4)

Environmental Impacts

Proper REM sleep is vital in making short term memories more long term. The network of information that the active neurons build during REM sleep can impact overall memory. One issue greatly disturbing this sleep is the environment that people live in. Those living in poverty or a dangerous neighborhood with high crime rates may experience more difficulties getting proper sleep in all stages of the cycle. Imagine living in a neighborhood with gangs venturing outside your door. Imagine living by train tracks with a train that speeds by every night. Perhaps you live in a city that never sleeps. These interruptions can disrupt a person’s sleep cycle, having negative implications on the ability of their neurons to strengthen that synaptic plasticity during REM sleep. A sleep environment should be a dark, cool, and quiet place; this is not necessarily easy for most of the population to check off before going to bed.2 There are over 648 million people in the world that live in extreme poverty, and even more that live in poor conditions comparable to that.3 That is a lot of people likely not getting the proper sleep due to their living conditions being in poor environments. Even cities with poorly insulated apartments can result in noises from neighbors that can disrupt sleep. The number of environmental reasons for sleep disruption is unbelievable.

Conclusion

Sleep is so important in the development of synaptic plasticity and memory consolidation through potentiation. While of course awake repetition of the learned information to transition the short term memory into a long one is important as well, sleep is a push towards really solidifying that memory without actively studying. In a sense, it almost feels like magic in how the mind works to build stronger neuron connections while we peacefully sleep. Of course, peaceful sleep is not a privilege everyone has and is a difficult issue to solve because of all the different factors contributing to the disruption.

 

Citations:

  1. Memory consolidation. (2020, August 28). Ian. https://human-memory.net/memory-consolidation/#Basics_of_Memory_Consolidation
  2. Creating a good sleep environment. (2021, June 29). CDC. https://www.cdc.gov/niosh/emres/longhourstraining/environment.html
  3. Schoch, M., Baah, S. K. T., Lakner, C., & Friedman, J. (n.d.). Half of the global population lives on less than US$6.85 per person per day. World Bank Blogs. Retrieved March 28, 2023, from https://blogs.worldbank.org/developmenttalk/half-global-population-lives-less-us685-person-day
  4. Feld, G. B., & Diekelmann, S. (2020). Building the Bridge: Outlining steps toward an applied sleep-and-memory research program. Current Directions in Psychological Science, 29(6), 554–562. https://doi.org/10.1177/0963721420964171

 

Why is Sleep Important?

 

Artstract by Jessica Howard

The Stages of Sleep  

There are four different sleep stages that are identified by the type of brain waves present during each stage (Patel, Reddy, Shumway, & Araujo, 2022). These brain waves range from high frequency to lower frequencies. The highest frequency wave is called the beta waves with the next highest being alpha waves. These waves are both present during wakefulness.  

Stage 1 of sleep, also know as non-REM 1, is the lightest stage of sleep and is marked by starting as alpha waves and moving into low voltage theta waves. During this stage there is still muscle tone and regular breathing rates.  

  Stage 2 of sleep is non-REM 2 and is a deeper sleep than non-REM1. Theta waves are the predominant brain wave during this stage. There are also sleep spindles and K complexes present during this stage. Sleep spindles are short bursts of neurons firing that possibly play a role in memory consolidation. K Complexes are brief delta waves, the longest of the brain waves, that are associated with maintaining sleep.  

Stage 3 of sleep is the deepest stage of non-REM sleep. During this stage there are Delta waves which are the lowest frequency of the brain waves. During this stage the body can repair tissue and strengthen its immune system. This is also the most difficult stage to awaken from, and when people are awakened during this stage they experience a state of mental grogginess.  

REM sleep stands for Rapid Eye Movement and is very different from the other stages of sleep. During REM sleep beta waves are present and is therefore not considered to be a restful stage of sleep. However, this is the stage where dreams occur. During this stage the muscles are paralyzed except for the eyes and diaphragm breathing muscles (Patel, et. al., 2022).  

Why is sleep important  

Sleep plays several functions in the overall health of the body. It gives the body a chance to rest and heal from the past day. But sleep also gives the brain a chance to sort through all the new memories that it has experienced and prepare for the new experiences of tomorrow. REM sleep and the deep stages of non-REM sleep seem to be the most important for consolidating the memories of that day (Wein, 2017). This is the time where the hippocampus (which is the part of your brain in charge of memory) is working to connect all of these memories together and get them stored permanently (Xia & Storm, 2017). Specifically, it seems that certain pathways inside the cells of the hippocampus are important for the formation of new proteins related to these old memories, which is how the memories seem to outlive the original proteins they were connected to. Pathways such as the MAPK cascade are activated by calcium (Ca) dependent NMDA receptors, which allow Ca to enter the cell when activated. As Ca enters into the cell through these receptors it depolarizes the cell which starts the MAPK pathway. As the cell depolarizes, or gains a more positive charge, this starts a series of reactions. Protein kinases, which are just enzymes, start to phosphorylate (or add a phosphorus molecule) to other protein kinases called Ras, Raf, MEK, and ERK. The phosphorylation of these enzymes causes them to change shape to activate each other, in the final step is the phosphorylation of a transcription factor called CREB. CREB can then enter into the nucleus and start gene transcription to make a new protein. This protein is then associated with a memory because it is from the hippocampus (Xia & Storm, 2017).

Xia, Z., & Storm, D. (2017). Role of circadian rhythm and REM sleep for memory consolidation. Elsevier: Neuroscience Research 118. 13-20. http://dx.doi.org/10.1016/j.neures.2017.04.011.  

Though the light stages of non-REM sleep also play an important role (Wein, 2017). These stages seem to be most connected to getting the brain ready to receive new information when it wakes up. When these stages are cut short the brain not only doesn’t have enough time to consolidate the old memories, it also doesn’t have time to prepare to receive the new information. This can drastically reduce your ability to retain information the following day, which is a big problem for students (Wein, 2017). 

How can you improve your sleep  

The best way to improve your quality of sleep and the amount of sleep you get is to maintain good sleep hygiene (Hershner & Shaikh, 2021). Sleep hygiene is just a term used to describe healthy sleep habits. It is important that you get enough sleep every night, while the exact amount of sleep varies from person to person it’s generally best to get 7-8 hours of sleep per night. It’s also important to remain consistent with your sleep schedule every single day. Try to go to bed and get up at the same times, even for the weekends and on vacation. If you have trouble falling asleep it may help to not have any caffeine after 12 pm and to turn off all your electronics 20 minutes before actually going to bed. Another thing you can do is to have an established bedtime routine that you do every single night. This will help to signal to your brain that it’s time for sleep, and it can start releasing hormones such as melatonin to make you sleepy (Hershner & Shaikh, 2021).  

  There of course are many more things you can try to help you improve your sleep quality, but the tips listed above can be a good place to start. It can by really hard to change your sleepy habits, especially when it comes to using electronics and staying up to late. But by sticking with a regular routine your brain will eventually become acclimated and it will become easier to get more higher quality sleep.  

References

Hershner, S., & Shaikh, I. (Eds.). (2021, April 2). Healthy sleep habits. Sleep Education. Retrieved March 27, 2023, from https://sleepeducation.org/healthy-sleep/healthy-sleep-habits/  

Patel, A. K., Reddy, V., Shumway, K. R., & Araujo, J. F. (2022, September 7). Physiology, sleep stages – statpearls – NCBI bookshelf. Retrieved March 28, 2023, from https://www.ncbi.nlm.nih.gov/books/NBK526132/  

Wein, H. (Ed.). (2017, July 13). Sleep on it. National Institutes of Health. Retrieved March 27, 2023, from https://newsinhealth.nih.gov/2013/04/sleep-it#:~:text=Memories%20seem%20to%20become%20more,may%20help%20with%20problem%2Dsolving.  

Xia, Z., & Storm, D. (2017). Role of circadian rhythm and REM sleep for memory consolidation. Elsevier: Neuroscience Research 118. 13-20. http://dx.doi.org/10.1016/j.neures.2017.04.011.  

Catch some Z’s

The Hippocampus

The specific region of the brain that helps to form new memories is called the hippocampus. Most memories formed here will be lost during the day, but sleep allows for memories to become more stable. During sleep, the brain cycles through different levels of sleep. These levels will be covered more in depth later. Dr. Robert Stickgold of Harvard Medical School says that ‘sleep seems to be a privileged time when the brain goes back through recent memories and decides both what to keep and what not to keep.” In Figure 1, it is noted that the hippocampus has less brain activity when a person is sleep deprived. On the other hand, hippocampus activity is much higher in those who are well rested.

Figure 1. Hippocampus activity based on sleep.

 

Stages of sleep

The stages of sleep that we cycle through are categorized as non-REM and REM sleep. REM stands for rapid eye movement, and this stage is where dreaming most often happens. On the other hand, non-REM sleep is thought to prime the brain for new learning. Like mentioned before, the hippocampus is important for making new memories. And, when a person is deprived of sleep, the hippocampus is negatively affected, making it hard to form new memories. Sleep scientist Dr. Walker says that “you can’t pull an all nighter and still learn effectively.” New memories are formed while we’re awake, and are strengthened as we sleep. 

Rapid eye movement (REM) sleep- rapid, low voltage theta waves, muscle atone

Non-REM sleep- slow wave, low frequency, large amplitude delta waves

Figure 2. Sleep stages.

The science of sleep 

Memory consolidation depends on Ca2+ activation of the cAMP/MAPK/CRE-mediated transcriptional pathway and protein synthesis. This pathway, as well as protein synthesis, undergoes a circadian cycle, a 24-hr cycle that responds to light and dark. If this process is disrupted in any way, memory formation decreases. REM sleep also activates this pathway which goes hand and hand with circadian cycles. Memories formed with the help of the hippocampus are maintained by reactivation of CREB-mediated transcription and protein synthesis during circadian cycles that occur during REM sleep. These events are all made possible by cAMP activation of the MAPK pathway. This pathway is pictured in the figure below and can be referenced more in depth in the article Role of circadian rhythm and REM sleep for memory consolidation.

Figure 3. cAMP/MAPK/CRE-mediated transcriptional pathway.

So, how do you get better sleep?

After reading this post, you may ask yourself what you can do to get better sleep? The answer is that there isn’t an exact answer, but there are plenty of things that can be done. Better sleep is correlated with better eating habits, and better physical health. The CDC has a great schematic for how much sleep a person needs based on their age. They also mention multiple tips for improving sleep; go to bed at the same time each night and wake up each morning at the same time, keep your room dark and quiet, avoid alcohol and caffeine before bedtime, and be physically active every day.

Figure 4. How to improve sleep.

References

How to get better sleep- CDC

Memory consolidation and sleep- PubMed

Sleep on it- how snoozing strengthens memories

Sleep stages

 

Cancer in the brain EXPLAINED

Glioblastoma is a type of cancer that starts with abnormal growth of cells in the brain or spinal cord that eventually turns into a tumor. Glioblastoma can occur at any age and symptoms may range from headaches, nausea and vomiting, blurred or double vision, and seizures. To test for glioblastoma certain tests can be performed such as a neurological exam, imaging tests like a positron emission tomography (PET), computed tomography (CT), or magnetic resonance imaging (MRI) scan, or performing a biopsy by removing a sample of the tumor tissue for testing.

Malignant brain tumor treatment could include surgery, radiotherapy, or intake of temozolamide (TMZ). Temozolamide works by crossing the Blood brain barrier, blocking DNA replication and cell proliferation, and functionally is an alkylating agent used to methylate DNA on the sixth position of guanine. For clarification malignant is not the same as bening, malignant is a cancerous faster growth that can reach the bloodstream to spread and wreak havoc on the body. Whereas, bening is a non cancerous slow growth that covers normal cells and doesn’t spread quickly to other parts of the body.

Pathway talk:

Figure 1 looks at the cAMP pathway which functions to regulate multiple cellular functions. To function a ligand binds to a G-protein coupled receptor (GPCR) activating the enzyme adenylyl cyclase to convert ATP to cAMP. cAMP then activates protein kinase A (PKA) to inhibit tumor growth. This pathway may also be activated via Phosphodiesterase inhibitors (PDEi) to promote apoptosis.

Figure 2 focuses on the PI3K pathway functions to regulate cell differentiation, adhesion, motility, invasion, proliferation, and survival. This pathway is activated by binding the ligand to the RTK receptor causing dimerization and phosphorylation of RTK. Then PI3K is recruited to RTK via regulatory subunit p85 and activates p110. Then this subunit p110 converts PIP2 to PIP3, which is regulated by PTEN, PIP3 activates AKT so AKT can undergo phosphorylation and activation. AKT signals to other portions of the pathway such as mTOR to complete the functions listed above.

The last figure, figure 3, is the MAPK pathway the molecule binds to an RTK receptor which then goes to GRB2 and SOS, converting GDP on RAS to GTP on RAS ultimately leading to cell proliferation, survival, and migration. As seen in figure 3 NF1 functions to regulate the pathway by converting GTP to GDP and inactivating RAS.

 

 

 

 

 

Figure 1: cAMP Pathway, Figure 2: PI3K pathway, Figure 3: MAPK pathway

In a new research study malignant tumor growth, also known as glioblastoma, impacts multiple signaling pathways such as MAPK, PI3K, and cAMP pathways. In tumor growth there is hyperactivation of MAPK and PI3K pathways well there is hyporegulation of cAMP pathways. Drug treatments that have been studied in the past target single  pathways, however cross talk of pathways combination drug treatments should be the new focus for treatment of glioblastoma. There have also been studies focusing on convergence of CREB and how that could impact tumor growth. While glioblastoma is a treacherous disease to combat there has been more research to look at other possible solutions.

 

Sources:

https://www.mayoclinic.org/diseases-conditions/glioblastoma/cdc-20350148

https://pubmed.ncbi.nlm.nih.gov/30710631/

The Blood Brain Barrier: Drug Delivery in Glioblastoma

The blood brain barrier (obemereier 2013)

The blood-brain barrier (BBB) is a highly selective and specialized membrane that separates circulating blood from the brain extracellular fluid (BECF) in the central nervous system (CNS). It is composed of tightly-packed endothelial cells lining the capillaries in the brain, as well as surrounding astrocyte cells, pericytes, and basal lamina.

The BBB plays a critical role in maintaining the homeostasis of the brain microenvironment by preventing the entry of many substances from the bloodstream into the brain, including toxins, pathogens, and most drugs.

In glioblastoma, the BBB becomes disrupted and leaky due to the formation of new blood vessels in the tumor, a process known as angiogenesis. The endothelial cells that make up the BBB become damaged and lose their tight junctions, allowing larger molecules to enter the brain. However, the tumor cells themselves can also actively modulate the BBB by secreting various factors that increase its permeability.

The disrupted BBB in glioblastoma can have both positive and negative effects on treatment outcomes. On the one hand, it allows certain therapeutic agents to cross the BBB and reach the tumor, which can improve treatment efficacy. And on the other hand, it allows the tumor cells to evade the immune system and promotes tumor growth in other body parts.

Researchers are actively studying ways to exploit the leaky BBB in glioblastoma to improve treatment outcomes. One approach involves using drugs that can selectively target the tumor cells while minimizing damage to healthy brain tissue. Another approach involves using nanoparticles that can bypass the BBB and deliver therapeutic agents directly to the tumor cells.

Nanocarriers have a wide range of applications. One example is their use in transporting small non coding mRNA molecules that target brain tumor tissue and stop proliferation. The nano carriers protect the RNA from nuclease degradation and promote effective regulation of target genes, especially in brain tumors such as glioblastomas (GBMs) that are somehow protected from chemotherapeutic drugs by the blood–brain barrier (BBB).

Nano carriers crossing the BBB (Dubois 2014)

This image attempts to clarify the action of miRNAs in brain-cancer cells, through nano carriers capable of crossing through the BBB.

A question that was brought up in class on Wednesday was whether or not this drug delivery technique is specific to the tumor cells, and does not damage other cells in the immediate vicinity of the tumor, and the answer to that I found in a research study that reviewed the use of CDs, nano particles in drug delivery. The review article reported that the over-expression of transferrin receptors on both tumor cells and the BBB’s endothelial cells allows CDs to be specifically targeted to cancerous cells when conjugated with transferrin.

The authors supported this by referencing Hettiarachchi et al, who designed a triple-conjugated CD-based nano carrier (DDS) that targeted glioblastoma with transferrin, epirubicin, and temozolomide. The results showed that a much lower concentration of the triple-conjugated system (C-dots-transferrin-epirubicin-temozolomide (C-DT)) was required to reduce tumor cell viability compared to non-transferrin systems (NT) and dual-conjugated systems, namely CDs-transferrin-temozolomide (C-TT) and CDs-transferrin-epirubicin (C-ET). These findings suggest that CDs can be loaded with multiple therapeutic agents, resulting in a synergistic effect on antitumor efficiency.

The ideal method for transporting drugs across the BBB would be controllable and not damage the barrier. Among the various presently available approaches, nano-biotechnology-based delivery methods are the most promising .

References:

Dubois et al. Researchgate.net. Retrieved March 24, 2023, from https://www.researchgate.net/publication/273138648_Gliomas_and_the_vascular_fragility_of_the_blood_brain_barrier

Obermeier, B., Daneman, R. & Ransohoff, R. Development, maintenance and disruption of the blood-brain barrier. Nat Med 19, 1584–1596 (2013). https://doi.org/10.1038/nm.3407

Qian, Z. M., Li, H., Sun, H., & Ho, K. (2002). Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacological Reviews, 54(4), 561–587. https://doi.org/10.1124/pr.54.4.561

Zhang, W., Sigdel, G., Mintz, K. J., Seven, E. S., Zhou, Y., Wang, C., & Leblanc, R. M. (2021). Carbon dots: A future blood-brain barrier penetrating nanomedicine and drug nanocarrier. International Journal of Nanomedicine, 16, 5003–5016. https://doi.org/10.2147/IJN.S318732

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