Cobbers on the Brain – Page 13 – Student Commentary on the Neurological Sciences

Insulin levels in Blood and Cerebrospinal Fluid

Posted on February 14, 2024 by zariye / 0 Comment

Research from as early as 1983 has documented changes in blood insulin levels in Alzheimer’s disease. Fasting blood insulin and insulin response to a glucose challenge are elevated in individuals with Alzheimer’s. This process in which insulin is transported from the blood to the brain is a receptor-mediated process and the receptor of insulin CSF serum shows a subtle decrease with age. The research also found lower levels of CSF/serum in AD and higher blood and lower CSF insulin to be more prominent with disease progression. Although findings on cerebrospinal fluid (CSF) insulin vary, recent data indicates that individuals with Alzheimer’s disease are likely to have increased blood insulin levels.

http://Gabbouj S, Ryhänen S, Marttinen M, Wittrahm R, Takalo M, Kemppainen S, Martiskainen H, Tanila H, Haapasalo A, Hiltunen M and Natunen T (2019) Altered Insulin Signaling in Alzheimer’s Disease Brain – Special Emphasis on PI3K-Akt Pathway. Front. Neurosci. 13:629. doi: 10.3389/fnins.2019.00629

http://Ray, Lori & Heys, Jeffrey. (2019). Fluid Flow and Mass Transport in Brain Tissue. Fluids. 4. 196. 10.3390/fluids4040196.

Uncategorized

Insulin Signaling in the Brain

Posted on February 14, 2024 by zariye / 0 Comment

Insulin enters the brain through one of three routes: blood-brain barrier, median eminence, or the vascular endothelium by transport proteins. Insulin levels vary throughout the brain, the olfactory bulb is thought to have the highest level, this is mainly due to the high concentration of IRs. When insulin and IR bind this, two branches of insulin signaling are activated, MAPK and PI3-Akt Pathways. IGF1R also activates PI3K. IR and IGF1R both belong to the RTK family. When insulin binds this causes the IR to change this change initiates autophosphorylation and attracts IRS proteins, while the IRS is being activated there are phosphorylation sites inactivating the IRS by making them separate from the insulin receptor and reducing the addition of phosphate groups to tyrosine. Tyrosine-phosphorylated IRS activates PI3Ks, PI3K is a heterometric protein, and its SH2 domain; P85 binds to phosphoserines, P110 changes phosphatidylinositol (3,4)-bisphosphate (PIP2) into phosphatidylinositol (3,4,5)-trisphosphate (PIP3), which results in the activation of many downstream kinases. Akt is from the family of serine/threonine kinases and consists of three isoforms, Akt1, Akt2, and Akt3. These forms showed varied expression in the brain and cells based on their location, an example is how Akt1 and Akt3 are distributed through somatic layers of the hippocampus, however, Akt2 is expressed in astrocytes instead and not neurons. Upon activation, Akt is activated with the PH domain of PIP3 and this then allows PIP3 to phosphorylate threonine. There was a study conducted that measured insulin in low levels of the brain; in humans and rodents, the research revealed that reductions in brain insulin were consistent in both Alzheimer’s patients and age-matched individuals without Alzheimer’s, suggesting that the decline in brain insulin is more likely associated with aging rather than specifically with Alzheimer’s disease. One study couldn’t find insulin mRNA in the cortex, while another study did, making it challenging to interpret the mRNA data. To fully understand insulin’s role in healthy and diseased brains, more research needs to be done to explore its relationship with the severity of Alzheimer’s disease and age-matched controls. However Ongoing studies consistently show that administering insulin, either through intravenous infusion or intranasal delivery, can slightly improve performance on memory tasks for both healthy adults and individuals with Alzheimer’s disease or mild cognitive impairment (MCI) at dosage levels.

http://How does brain insulin resistance develop in Alzheimer’s disease? – Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Impaired-neuronal-insulin-signaling-in-Alzheimers-disease-AD-Schematic-outline-of_fig1_260215925 [accessed 14 Feb, 2024]

http://Stanley, M., Macauley, S. L., & Holtzman, D. M. (2016). Changes in insulin and insulin signaling in Alzheimer’s disease: cause or consequence?. The Journal of experimental medicine, 213(8), 1375–1385. https://doi.org/10.1084/jem.20160493

Disease

Alzheimer’s Disease and Precursors; the Impact of Nutrition

Posted on February 13, 2024 by speders4 / 0 Comment

Figure 1: Alzheimer’s disease[1]

Alzheimer’s disease (AD) is one of the most common diseases related to decline in cognitive abilities, but at the same time its causes and hallmarks might be unknown to most people. AD is a gradual and progressive neurodegenerative disorder, which tends to affect the older population. Deficits related to this disorder is such of memory, language, attention, reasoning, comprehension, and judgement[2]. Generally, the decline in cognitive abilities can be defined by the term dementia, however, AD is the most common type of dementia. Pathological AD hallmarks can be categorized as amyloid-β-plaques (clumps of beta amyloid protein) and neurofibrillary tangles (bundles of tangles made up by tau protein) that develops in the brain[3]. A neuromodulator in the brain that has been revealed to be one of the factors of cognitive impairment and the AD pathology is dysregulated brain insulin signaling[4].

Figure 2: The comparison of a normal brain versus the AD brain, with the formations of neurofibrillary tangles and amyloid plaques. [5]

The progression of AD can be seen as a process with many implication factors, as understood with the implications with insulin signaling, but the process of AD is related to some precursors that can start already at the level of healthy eating patterns. Studies have found that a healthy diet is associated with a lower risk of AD[6]. A list of nutrients has been found to have a beneficial effect on the course of AD, such as vitamins B6, B12, folic acid, polyphenols, while on the other hand for example fatty acids promotes the progression of the disease[7]. Additionally, a study found that plant-based diets such as the Mediterranean diet, were associated with lower levels of oxidative stress and inflammation in comparison to a fast-food diet[8]. Healthy diets can be believed to affect underlies mechanisms such as oxidative stress and neuroinflammation[9], which further play a role in influencing pathways, the formation of plaques, and neural death[10]. The formation of plaques (tau accumulation) and neural death contribute to the formation of tangles inside the neurons which is a part of the progression of AD.

Figure 3: The impact of nutrition on the brain. [11]

In relation to both healthy lifestyle and impaired insulin signaling is diabetes type 2, which is a result of both of these. It has been found that people who suffer from diabetes type 2 have a higher likeliness for the progression of AD, because of the strong correlation[12]. So, the process starting at the food one consumes, can play are role in the progression of AD, and the different precursors and factors that play a role in the progression of AD. As can be seen with the interconnecting pathological features of neuroinflammation and insulin resistance that are two of the major factors of synaptic disruption and neurogenerative processes[13]. Diabetes connects with the insulin resistance, and nutrition play are role in the development of diabetes type 2 and neuroinflammation, which can all be tied to the progression of AD.

A big factor with Alzheimer’s disease is time, since there is no cure or treatment that will heal the disease, we are looking for options to give Alzheimer’s patients a longer time to live, maybe even a better quality of life. One of these options can be understood to be nutrition, and your lifestyle. Therefore, interventions should or could be implied as early as possible to minimize the development of the disease. By looking at small bits of the progression of this disease, hopefully we are slowly understanding more on how to deal with Alzheimer`s disease.

[1] What is Alzheimer’s Disease? (n.d.). YouTube. https://www.google.com/url?sa=i&url=https%3A%2F%2Fwww.youtube.com%2Fwatch%3Fv%3D7F-t9yvPP_0&psig=AOvVaw01G76eZhQmR8VmBscxeREB&ust=1707882712431000&source=images&cd=vfe&opi=89978449&ved=0CBMQjRxqFwoTCMDYuYa1p4QDFQAAAAAdAAAAABBV
[2] Kumar, A., Sidhu, J., Goyal, A., et al. Kumar, A. (2022, June 5). Alzheimer Disease. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK499922/
[3] What happens to the brain in Alzheimer’s disease? (n.d.). National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/what-happens-brain-alzheimers-disease
[4] Akhtar, A., & Sah, S. P. (2020). Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer’s disease. Neurochemistry International, 135, 104707. https://doi.org/10.1016/j.neuint.2020.104707
[5] Amyloid Plaques and Neurofibrillary tangles | BrightFocus Foundation. (2015, July 1). https://www.brightfocus.org/news/amyloid-plaques-and-neurofibrillary-tangles
[6] Hu, N., Yu, J. T., Tan, L., Wang, Y. L., Sun, L., & Tan, L. (2013). Nutrition and the risk of Alzheimer’s disease. BioMed research international, 2013, 524820. https://doi.org/10.1155/2013/524820
[7] Śliwińska, S., & Jeziorek, M. (2021). The role of nutrition in Alzheimer’s disease. Roczniki Panstwowego Zakladu Higieny, 72, 29–39. https://doi.org/10.32394/rpzh.2021.0154
[8] Aleksandrova, K., Koelman, L., & Rodrigues, C. E. (2021). Dietary patterns and biomarkers of oxidative stress and inflammation: A systematic review of observational and intervention studies. Redox Biology, 42, 101869. https://doi.org/10.1016/j.redox.2021.101869
[9] Aleksandrova, K., Koelman, L., & Rodrigues, C. E. (2021). Dietary patterns and biomarkers of oxidative stress and inflammation: A systematic review of observational and intervention studies. Redox Biology, 42, 101869. https://doi.org/10.1016/j.redox.2021.101869
[10] Akhtar, A., & Sah, S. P. (2020). Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer’s disease. Neurochemistry International, 135,104707. https://doi.org/10.1016/j.neuint.2020.104707
[11] What we know about Alzheimer’s disease and nutrition. (n.d.). Nutri-facts. https://www.nutri-facts.org/en_US/news/articles/what-we-know-about-alzheimers-disease-and-nutrition.html
[12] Akhtar, A., & Sah, S. P. (2020). Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer’s disease. Neurochemistry International, 135,104707. https://doi.org/10.1016/j.neuint.2020.104707
[13] Ibid.

Disease

Alzheimer’s Disease and Insulin Resistance

Posted on February 13, 2024 by Olivia / 0 Comment

Figure 1. Photo: The George-Anne Media Group

What Is Alzheimer’s Disease?

Alzheimer’s disease (AD) is a neurological condition that causes millions of people to suffer from cognitive deficits. There is not a set answer for treating and preventing the disease as the pathology is still not completely understood, however, there are a few different theories pertaining to the development of the disease. One of the theories is that dysfunction within the insulin signaling pathway is responsible for the pathogenesis of Alzheimer’s disease. [1]

The two main biomarkers of Alzheimer’s disease are β-amyloid plaques and neurofibrillary tangles (NFT). NFTs are the result of tau proteins becoming hyperphosphorylated, causing them to clump together and disrupt the function of the microtubules. When the microtubules are not working properly, the neuron cannot work properly. β-amyloid plaques are formed by amyloid precursor proteins (APP) and can compete with insulin in binding to insulin receptors, causing dysfunction. Both NFTs and β-amyloid plaques have a role in insulin resistance. [1]

Figure 2. Neurofibrillary tangles and β-amyloid plaques compared to a healthy neuron. Photo: Wikimedia Commons. **Insulin and the Brain**

While insulin was once thought to not have any prevalence in the brain, we now know that there are concentrations of insulin and insulin receptors in some brain regions. Insulin can be synthesized in the brain and can also cross the blood brain barrier. It has a regulatory role in neuroprotection. Insulin also plays a role in memory and learning and has been shown to regulate the accumulation of amyloid β. Some studies have found that dysregulation of glucose metabolism can lead to memory loss and dementia symptoms of AD. [1]

AD and the Insulin Signaling Pathway

There are multiple components throughout the insulin signaling pathway that could be possible sites for AD pathogenesis. Irregularities and dysfunctions regarding these components can lead to the development of AD symptoms including dementia and deficits with working memory and learning. For example, mTOR is a protein involved in the PI3K pathway triggered by growth factors to regulate metabolic activity. Another example is that when GSK-3β is phosphorylated, it facilitates the formation and accumulation of β-amyloid plaques as well as the accumulation of phosphorylated tau proteins leading to NFTs. Amyloid β has also been found to activate GSK-3β which can lead to even more phosphorylated tau proteins. [1]

Figure 3. The insulin signaling pathway is composed of a variety of molecules. Here we can see some of those molecules like PI3K and GSK3 that may have a contribution to the development of Alzheimer’s disease. Photo: Wikimedia Commons.

The article Insulin signaling and AD described an AD mouse model that showed evidence of irregularities in mTOR signaling and that phosphorylated mTOR was elevated in AD subjects. Several of the dysregulated molecules lead to the production and accumulation of β-amyloid plaques and neurofibrillary tangles which are key factors of Alzheimer’s disease. [1]

Is Insulin Resistance Responsible for AD?

While there is substantial evidence for insulin resistance being a probable cause to Alzheimer’s disease, there are still some things researchers need to evaluate. Insulin resistance has been shown to increase other things that have been hypothesized to contribute to the development of Alzheimer’s. These things include oxidative stress, the production of cytokines, and process leading to cell death. Insulin resistance may be a great theory as to why neurological diseases like Alzheimer’s occur but may also just influence other forces that contribute to the disease. [1]

Lifestyle as Prevention

Alzheimer’s disease is not the result of one sole issue. Insulin resistance can begin in the body through a variety of circumstances. Diabetes mellitus is a more commonly known form of insulin resistance, but can also develop from an excessive caloric intake and/or a high-fat diet. Insulin resistance can also develop due to physical inactivity. Making a conscious effort to maintain a healthy lifestyle has a lot of benefits regarding the prevention of neurodegenerative diseases like Alzheimer’s. [2]

[1] A. Akhtar and S. P. Sah, “Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer’s disease,” Feb. 21, 2020. [Online]. Available: https://doi.org/10.1016/j.neuint.2020.104707

[2] U. Pagotto, “Where Does Insulin Resistance Start?: The brain,” Diabetes Care, vol. 32, no. suppl_2, pp. S174–S177, Nov. 2009, doi: 10.2337/dc09-S305.

Uncategorized

Alzheimer’s Disease and Diet as Prevention

Posted on February 12, 2024 by Kelly / 0 Comment

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/.

Disease

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

Posted on February 12, 2024 by kloidolt / 0 Comment

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.

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).

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.

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.

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 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

Uncategorized

Anything but an ordinary four years

Posted on May 9, 2023 by / 0 Comment

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.

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.

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.

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.

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.

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,

Health/Spirituality

Unlocking Brain’s Potential: Exploring the World of Nootropics

Posted on May 6, 2023 by / 0 Comment

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

Hot topics

The News on Nootropics

Posted on May 6, 2023 by / 0 Comment

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.

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

Uncategorized

The End to Pain Through Endocannabinoids

Posted on May 5, 2023 by / 0 Comment

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 Neuroscience, 10. 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)