AP Biology class blog for discussing current research in Biology

Tag: Neurodegeneration

The Dark Truth of Athletic Industry: The Effects of Anabolic-Androgenic Steroids on the Brain

Decades ago, the use of performancing-enhancing drugs, or PEDs, had been reserved for use by only the most elite of athletes, including bodybuilders and competitive sports players. In this day in age, however, PEDs have become ubiquitous amongst not only competitive athletes, but also regular gym-goers. As they play such a drastic role in the betterment of athletic performance, the benefits of PEDS are not without a trade-off: they have innumerable dangerous health consequences that must be understood. 

But what are PEDs in the first place? The most common form of PEDs comes in the form of anabolic-androgenic steroids, or AAS, which are derivatives of the male sex hormone testosterone. In a performancing-enhancing context, AAS such as pure testosterone are used to increase systemic androgenic activity in the body, manifesting in the hyper-development of male sexual characteristics such as hair growth, acne development, low voice, muscularity, and libido. By taking AAS, athletes are also able to reap the competitive benefit of erythropoiesis, or the production of red blood cells, increasing athleticism and endurance. In addition to overall increase in testosterone, many forms of testosterone derivatives other than pure testosterone, have anabolic, tissue-selective properties, directly leading to an increase in muscle mass. By taking AAS, athletes are able to give themselves a competitive edge in beating their counterparts. 

However, the effects of AAS on the body also have overwhelming negatives. It is widely known that taking AAS in the form of exogenous testosterone can shut down endogenous androgenic activity, leading to symptoms such as shrunken testicles, breast tissue development, and low energy. In addition, a new study conducted by Oslo University Hospital suggests that AAS can also lead to premature aging of the brain

Due to their chemical structure, after being injected using a needle into the blood, AAS enter the brain very easily. As steroids, AAS are hydrophobic, non-polar molecules, meaning they are able to passively diffuse through the phospholipid bilayer of cells through passive transport, depending upon concentration. At Oslo University Hospital, Dr. Bjørnebekk and his colleagues lead a study to investigate the effects of AAS on brain aging by scanning the brains of patients with past AAS use and those without it using MRIs. In the study, Dr. Bjørnebekk tested the brain age gap, or the difference between a patient’s chronological age and their predicted brain age, with a high brain age gap marking a higher risk for cognitive disease. Across the board, the AAS group showed significantly higher brain aging, or higher brain age gap, than standard participants, illustrating the underlying risks involved with AAS use. 

While the detrimental effects of exogenous AAS abuse are widespread across the body, unfortunately, technology to aid in the success of PED-using athletes has been flourishing in recent years. As exogenous AAS use often leads to crashed endogenous testosterone production in men, PCT, or Post-Cycle Therapy, drugs have been created to help men regain normal endogenous testosterone production after exogenous steroid abuse. Since AAS users usually experience low testosterone and high estrogen levels, estrogen blockers, such as Clomid or Nolvadex, are used in PCT to regain natural hormonal balance. While this may address the acute hormonal consequences of AAS use, technology, as of now, has not yet been created to ameliorate the long-term effects of AAS use on the brain. Manifested in the higher incidence of brain age gap in AAS users in the study, the neurodegenerative effects of AAS cause neurons to gradually lose function and die, which is often permanent. In conclusion, while PEDs in the form of AAS do exhibit strong competitive benefits for athletes, their long-term negative consequences and role in the acceleration of neurodegeneration make using AAS an unwise choice. 

Depo-testosterone 200 mg ml crop

New Developments in the Biology of Alzheimer’s Disease

Recent work by Boston University School of Medicine researchers shows developments in a new model for the biology of Alzheimer’s disease, which could lead to entirely new approaches in treating the disease. Alzheimer’s disease disrupts one’s cognitive abilities, including memory, thinking, and behavior. It accounts for 60-80% of all dementia cases. The neurodegenerative disease is caused by clumps and accumulations of 2 proteins –beta-amyloid and tau– which cause nerve cell injury and in turn, dementia.

Comparison of a normal brain (left) and the brain of a person diagnosed with Alzheimer’s (right).

Recent work by the BUSM researchers has shown that the clumping and accumulation of the tau protein are largely due to stress. The accumulation of tau produces “stress granules” (RNA/protein complexes). The brain responds to these stress granules by producing important protective proteins. However, with excessive stress, there is a greater accumulation of stress granules, which in turn leads to greater accumulation of clumped tau, which causes nerve cell injury. In this study, researchers are using this model to show that reducing the level of stress granules could lead to improved nerve cell health. It may be possible to reduce the level of stress granules by genetically decreasing TIA1, a protein required for stress granule formation.

In an experimental model of Alzheimer’s disease, the research team found that reducing the TIA1 protein led to striking improvements in memory and life expectancy. However, although stress granule levels decreased (leading to better protection), the team observed that the clumps of tau became larger. The researchers further looked at the tau pathology and found that the while small clumps of tau (known as tau oligomers) are toxic, larger tau clumps are generally less toxic. According to pharmacology and experimental therapeutics professor Benjamin Wolozin, this discovery would explain why the experimental models experienced better memory and longer life expectancy. The implications and ability of TIA1 protein reduction in order to provide protection may lead to further novel developments in the biology and treatment of Alzheimer’s disease.


Identical Twins, Identical Lives, Different Disease

Jack and Jeff Gernsheimer are identical twins. Jack has Parkinson’s disease, and his twin Jeff does not. Up until recently, because they have identical genomes, it would have been a mystery as to why Jack could develop Parkinson’s but not Jeff. However, with the discovery of epigenetics, scientists know that genes alone cannot explain why some people get Parkinson’s and other do not. While there are some genetic mutations linked to Parkinson’s, 90 percent of cases are “sporadic”, meaning that the disease did not run in the family. Even twins often do not develop Parkinson’s in tandem. Naturally, if genes don’t explain the development of Parkinson’s, scientists look to environment. There are several environmental factors that are known to link to the disease. People who were POW’s in WWII, for example, have a higher rate of developing Parkinson’s. But, and here’s the interesting part, Jack and Jeff have lived almost identical lives. For almost all of their lives, they have lived less than half a mile apart. Throughout their lives, they have been exposed to the same air, water, pesticides, etc. When they grew up, they built homes five minutes apart (by walk) on their father’s farm in Pennsylvania. Then, when they entered the professional life, they co-founded a design firm, working with their desks pushed up against each other.


This anomaly, where a pair of humans exist with the same genetics and the same environment yet only one of them got sick is a research “bonanza” for scientists. All expected variables are being held constant, thus whatever is left must be deeply linked to the origins of Parkinson’s. However, there was a small difference in their lives that could provide insight into this anomaly. in 1968, Jack was drafted into the army and Jeff was not. This led to a series of unfortunate events in Jack’s life: first he served two years stateside in the military, got married, had two children, became involved in a long divorce, and suddenly his teenage son died. After this traumatic event, Jack went on to develop Parkinson’s, glaucoma, and prostate cancer, none of which Jeff has.

Jeff and Jack have been more than willing to undergo several studies in hope of finding something that could alleviate Jack’s Parkinson’s. The first study involved collecting embryonic stem cells from the twins. The benefit of stem cell cultures is that they act similarly to how they would in the body even though they are in a petri dish. The mid-brain dopaminergic neurons grown from Jack’s cells created abnormally low amounts of dopamine. Jeff’s produced normal amounts. Surprisingly, even though Jeff showed no signs of Parkinson’s, both twins had a mutation on a gene called GBA. This gene is known to be associated with Parkinson’s. As a result, both of their brain culture cells produced half the normal amount of beta-glucocerebrosidase, an enzyme linked to that gene. Instead of answering questions, this study only raised more to the fascinating case of Jeff and Jack.

I want to add a bit about how Jack’s son died, because it is unimaginably tragic and can show you just how much Jack had to face. Especially if we are considering Jack’s trauma as a contributor to his development of Parkinson’s, it is important to know the story. When Gabe, Jack’s son, was 14 in 1987, he became fascinated with the Vietnam War. Like any good father, Jack rented his son some movies on the war. One of those being The Deer Hunter, in which there is a scene where two prisoners of the Viet Cong are forced to play Russian Roulette. Gabe told his friend that if it were him, he wouldn’t just sit there. He would rather just get it over with. With that conversation, Gabe got his dad’s pistol, that he knew was hidden in the closet drawer, put one bullet in the chamber, put the gun to his head, and shot.

Jack rarely shows emotion. This “pressure cooker” way of dealing with things could explain his illness. Jeff thinks that the parkinson’s is a physical manifestation of how Jack deals with stress, rather how he doesn’t deal with stress. The connection between stress and disease is a very active research topic. And while their lives were very similar, if compared, Jack’s is by far the life with a more stressful environment. Some research might suggest that this stress differential can have a relation to Parkinson’s disease. In 2002, neuroscientists at UPitt subjected rats to stress, and they found that the stressed rats were more likely to experience damage to their dopamine-producing neurons than the non-stressed rats. This led to the term “neuroendangerment”, which means “rather than stress producing damage directly and immediately, it might increase the vulnerability of dopamine-producing cells to a subsequent insult.”

Another hypothesis as to what caused Jack’s Parkinson’s is that it could be linked to chronic inflammation.  Chronic inflammation is the mechanism by which stress can create neurodegeneration. Evidence that suggests this could be the case in Jack and Jeff is presented in their skin. Jack has psoriasis, a condition linked to chronic inflammation, and Jeff does not.

To this day, the search for what caused Jack’s Parkinson’s continues. Last year, NYSCF scientists conducted a study on the twins’ stem cells. They found a few functional differences between their cells. After finding the GBA mutation, they searched harder for other clues as to what might differentiate their brains. They screened 39,000 SNV’s, single nucleotide variants, which are instances where a single nucleotide in the human genome has been altered (either switched, deleted, or duplicated). They found 11 SNV’s, nine of which are linked to Parkinson’s disease. However, all 9 were found in both twins, meaning that this did not explain why Jack was sick and Jeff wasn’t.

Finally, they were able to uncover a relevant difference. Jack had high levels of MAO-B, which is involved in the breakdown of dopamine, whereas Jeff’s levels were close to normal.This hypothesis supposed that there exists a possible molecular mechanism by which stress could lead to neurodegeneration. What’s nice about this finding is that it could present a possible treatment for Parkinson’s. MAO-B inhibitors exist and are actually drugs currently on the market. They were given to Jack, and while it’s too soon to see the effects and to recommend them as treatment for Parkinson’s disease, it’s definitely a start.


Human skin cells reprogrammed directly into brain cells



Original article:

Some key words:

Neurodegenerative diseases: Disease such as Alzheimer’s, Parkinson’s and Huntington’s disease that undergo a neurodegenerative process, specific neurons are targeted for degeneration.

Spiny brain cell: The desired end brain cell in this study, and a brain cell affected by Huntington’s disease


In a study by the researchers at Washington University School of Medicine in Saint Louis, they demonstrate a way for human skin cells to be specifically converted to a type of brain cell. This study can help in the rehabilitation of people with Huntington’s disease by turning skin cells in to brain cells that are lost through this neurodegenerative disease. This is all accomplished without passing through the stem cell phase preventing other cell types forming.

This research involved adult skin cells that Yoo, the senior author, and his colleagues reprogrammed by using two microRNAs: miR-9, and miR-124. These micro RNAs open up the otherwise tightly packaged and inactive sections of the gene critical to the formation of brain cells. While the micro RNAs open up genes used for the creation and functionality of neurons, transcription factors taken from a part of the brain where medium spiny neurons are common directs the newly formed brain cells to a specific subunit of brain cells. The researchers then observed that the newly formed brain cells behave and function in a similar way to the native medium spiny neurons in mice, allowing this study to proceed in to further stages of experimentation, and hopefully result in a treatment practical for human use.

This study is very critical in the advancement of the treatment for neurodegenerative disease such as Huntington’s disease. Using different transcription factors from parts of the brain, alternate types of brain cells can be created to replace cells lost from neurodegenerative effects. This form of treatment will also prevent rejection of the transplant because the skin cells can be taken from the patient’s own body. This is a breakthrough in our pursuit of cures for these lethal neurodegenerative diseases.

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