Cobbers on the Brain

A common problem underlying many neurodegenerative diseases such as ALS, Alzheimer’s disease, and Parkinson’s disease is an abnormal accumulation of proteins in neurons.

In Parkinson’s the protein alpha-synuclein (pictured below) builds up in large masses called Lewy bodies. These bodies are toxic to the cell and can lead to cell death seen in Parkinson’s disease.

Parkinson’s Disease was first described by Dr. James Parkinson in 1817. The gene PARK encodes for the protein parkin (appropriately named after Dr. Parkinson). Parkin is a component of a clean-up system of the cell called the Ubiquitin Proteasome System or UPS (basically a fancy name for the garbage man of the cell). When a protein has an error or isn’t functioning properly, it is marked for death and the UPS system comes around to destroy it.  But because parkin is involved in this mechanism, it is not working properly in patients with Parkinson’s which allows the buildup of proteins leading to cell death.

(a proteasome chewing up a purple protein)

The current treatment for Parkinson’s disease is the drug L-DOPA which only deals with side effects of the disease and not the underlying protein build up. Parkinson’s specifically affects dopaminergic cells so they are not able to release sufficient amount of dopamine. Treatment with L-DOPA can help increase levels of dopamine in these patients and improve quality of life.

While there are many other molecular pathways thought to be involved in the progression of Parkinson’s this main concept of protein buildup is similar to that of other diseases. If we want to combat these neurodegenerative diseases, we can look into boosting our cells UPS system which naturally fights protein aggregation. In relation to Parkinson’s research, there are promising trials for drugs that will target and inhibit certain steps in the pathogenesis of Parkinson’s Disease specifically.

Michael J. Fox has started a foundation dedicated to finding the cure for Parkinson’s. He was diagnosed in 1991, and has been a large advocate for funding research since he released the statement of his diagnosis. They have raised $700 million for research programs for Parkinson’s. https://www.michaeljfox.org/

A concussion usually occurs from a blow to the head resulting in symptoms including a possible temporary loss of consciousness, headache, confusion, nausea, and/or fatigue. At the cellular level, a concussion is causing microstructural injury to neural tissue in the brain. Axonal injuries caused by concussions can impair cognitive function, reaction time, spatial learning, and memory. Furthermore, concussions can impair brain function through energy malfunction, inflammation, and altered protein degradation.

After sustaining a concussion, cellular changes such as increases in ionic fluxes, indiscriminant glutamate release, and metabolic changes are thought to last up to 10 days. While the brain is still recovering from the injury, it is vitally important to protect the head and refrain from participating in a situation that could result in another blow to the head. Unfortunately, getting hit a second time during cellular unrest could result in injuries far worse than concussion symptoms.
 
Second impact syndrome (SIS) occurs when someone has recently sustained a head injury and another impact is taken to the head before the symptoms of an initial concussion have subsided. SIS is particularly devastating because it can result in death or severe disability. SIS is rare and there is little epidemiological data for the disease, likely because there is controversy over the definition of SIS.
 
When the patient sustains a “second impact,” the brain loses its ability to auto regulate intracranial and cerebral perfusion pressures due to the cellular changes in ion fluxes, glutamate release, and metabolic changes from the initial concussion. In severe cases of SIS, this may lead to cerebral edema followed by brain herniation. Death has been reported to occur in a matter of two to five minutes, usually without time to stabilize or transport an athlete from the playing field to the emergency department. Prevention of SIS occurs when a player is not allowed to return to a contact sport while still showing signs of concussion.
 
Resulting in the phrase: “When in doubt, sit them out”
 
This seems like a reasonable way to think about prevention after sustaining a concussion. Unfortunately, however, a concussion diagnosis isn’t always straightforward and clear. For example migraines have several symptoms in common with those of a typical post concussion. So how do you definitively know if someone has a headache/migraine or if they have symptoms of a concussion when they are consistently participating in situations of high probability contact?

Concussions also don’t have a testable biomarker and imaging of the brain is expensive and not always conclusive. Instead, in most cases, a health professional will diagnose a concussion based on the patient’s emotions and their outward expressions of symptoms. This isn’t fool proof, however, since symptoms of concussions can vary from person to person. In addition, patients might not always be truthful of their symptoms. For example, an athlete may hide their symptoms of concussion in order to continue to get playing time.
 
With so much on the line, a concussion should not be taken lightly. It is important for athletes, coaches, and parents to know the signs, symptoms, and life changing injuries that can be caused by concussions. Education of concussions might be the best way to make sure that everyone is on the same page of what kind of action to take in the event of a concussion. In this case, the most important action taken in the event of a head injury should be: “when in doubt, sit them out.”
 
 

Lou Gehrig was born on June 19, 1903 in New York City.  He was the son of two German immigrants, Christina and Heinrich Gehrig.  In his youth he showed incredible promise in the sports of football and baseball, which ultimately led to a football scholarship at Columbia University.  While attending Columbia he also joined the baseball team where he became known as “Columbia Lou” for his incredible pitching ability and his uncanny ability to hit home runs.  These abilities ultimately led him to joining the Yankees in 1923 with the likes of Babe Ruth and Joe DiMaggio.  He was deemed the “Iron Horse” by his teammates and his fans for his determination to play in spite of injuries.

In his career he boasted a lifetime batting average of .340 and in 1934 he won the batting “Triple Crown”.  This is when a player leads the league in runs batted in, home runs, and batting average.  He also, helped the Yankees to win six World Series championships.  However, his career was cut short when in 1938 he noticed he was having trouble tying his shoe laces and was diagnosed with ALS by the Mayo Clinic in Rochester, MN.  He retired the following year and died in his sleep on June 2, 1941.
Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disease that affects motor neurons in the brain and spinal cord.  It was first discovered in 1869 by Jean-Martin Charcot, a French neurologist.  However, it was not in the public eye until Lou Gehrig was diagnosed in 1939, effectively ending his career.  ALS usually presents itself between the ages of 40-70 and currently 20,000 people in the United States have the disease.

The disease itself is split into two categories: sporadic ALS and familial ALS.  Sporadic ALS is most common and makes up about 90-95% of all cases.  However, one of the gene mutations found in familial ALS is quite common in sporadic ALS.  ALS is caused by oxidative stress that can cause oxidative damage to proteins, lipids, and DNA.  This oxidative stress is caused by Reactive Oxygen Species (ROS) that are a by-product of your body’s normal functions.  In your body Mitochondria produce ATP and energy that your cells use to survive, and as a result ROS are produced as well as other molecules that can cause oxidative stress.  If this oxidative stress is countered by your body it can cause problems and diseases such as ALS.
Your body has natural antioxidants such as SOD1 that turn ROS into normal molecules that are found in your body.  When there are mutations in these molecules, or they are malfunctioning this can lead to an accumulation of ROS that can cause damage to motor neurons, mitochondria, and RNA/DNA.  This damage to RNA/DNA can cause further problems in other natural processes that can accelerate ALS.
ALS is a terrible neurodegenerative disease that does not have a cure and the only hope is to prolong life as long as possible.  Please visit www.alsa.org to donate or participate in a fundraiser to fight this disease.

Drug addiction is a chronic, debilitating disease that has become a serious issue in our society.  Prolonged substance abuse can result in both long-term chemical and structural changes in the brain. The reward pathway and the “feel good” neurotransmitter, dopamine, are heavily involved in this process. The pleasure felt from taking these addictive drugs is due to an increase in dopamine release. More intracellular dopamine results in more receptors which strengthens the synapse, or increases long-term potentiation. When this happens, more of the stimulus is required for the same pleasurable effect. Soon, you become dependent on the stimulus, as its absence can result in withdrawal symptoms.

Addiction is a vicious cycle and can seem completely hopeless for those trying to recover, but there are some effective ways to fight against it. These treatments include preventative measures, rehabilitation, and medication.
 
Technically, the most effective way to prevent addiction from occurring is to not try the substance in the first place. I know, way easier said than done, as some situations are completely out of control. Many become addicted to prescription drugs after needing them for some sort of medical treatment. Then, once their prescription runs out or expires, they realize they are dependent and often look to street drugs (ex. heroine) as replacement. However, there are scenarios of recreation, where the user is either not thinking about the risk or believes there is no chance they will become addicted after one time. Sadly, they are frequently mistaken.

Once an addicted individual seeks treatment, the first step is to go through a process of detoxification, often at a rehabilitation center to help with withdrawal symptoms. When the substance has left the body, there are a few different rehabilitation options available:

1. Inpatient Rehab refers to a more short-term program that allows patients access to healthcare professionals at all times, similar to a hospital stay. Often used in severe cases immediately after detoxification, this option gets rid of external distractions and responsibilities to allow the patient to focus solely on the recovery process. Often times, patients can be given medications to help with any lingering side effects, as well as starting some cognitive behavior therapy to understand their thoughts and feelings that may contribute to their behaviors.
2. Outpatient Rehab is more of a long-term program and gives the patient a little more freedom, as they just have to come in to the rehabilitation center at scheduled times for progress reports. There is also more emphasis on cognitive behavior therapy.
3. Social Programs consist of support groups to give patients a sense of community through sharing stories and experiences. Members can also work to keep each other accountable in living a better life and continuing sobriety.

Now, these treatment methods are not foolproof. Many relapse into their old habits after returning to their normal lives, as they still encounter the same old environmental cues and triggers. Treatments are also most effective when the addict truly wants to make a change in their life, as compared to being forced into treatment unwillingly.
 
While genetics don’t play a major role in addiction, they can make an individual more or less susceptible to developing addictive behaviors. For example, there are some genetic mutations that result in very unpleasant side effects to certain drugs or alcohol. As to be expected, these individuals are much less likely to abuse that substance and become addicted compared to someone who has no negative experience. It is interesting to think about the possibility of inducing these mutations in people as preventative measures, especially if there is a family history of addiction or alcoholism.

I cannot speak from experience, but I have watched close friends battle through the recovery process for drug addiction. It’s daunting, it’s ugly, and it definitely isn’t easy. It’s also extremely discouraging how high chances are for relapse, BUT, I’m here to tell you that it is possible and there is hope.