Concern About Concussions

 

Artstract created by T. Courier

What is a Concussion?

Concussions are a type of traumatic brain injury. In 2014 there were approximately 2.87 million concussions in the United States, but many people fail to receive treatment for concussions. Symptoms include headache, loss of consciousness, ringing in the ears, nausea, slurred speech, and fatigue. These symptoms can last for a few days after the incident to weeks or months later. https://www.mayoclinic.org/diseases-conditions/concussion/symptoms-causes/syc-20355594

Concussions happen when impact to the head causes the brain to forcefully make contact with the skull. This causes a myriad of effects within the brain. The neurons in the brain depolarize and there is a release of excitatory neurotransmitters, causing further depolarization. Ions rush out of the cell and the activity of the enzyme that break ATP into ADP. This causes the mitochondria to go into overdrive in an attempt to restore normal levels of ATP in the cell. Calcium also rushes into the cell and is stored in the mitochondria which makes it more difficult for them to produce ATP, causing a decrease in production. This can lead to apoptosis and a loss of neurons. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479139/ The loss of neurons is believed to lead to chronic traumatic encephalopathy which is seen in people who have sustained multiple traumatic brain injuries.

Chronic Traumatic Encephalopathy (CTE)

A diagnosis of CTE can only be made during an autopsy. However, there are some behavioral characteristics associated with CTE. These include difficulty thinking, impulsive behavior, short-term memory loss, emotional instability, substance abuse, and suicidal ideation. Many cases of CTE that have been studied occurred in football players, boxers, or military personnel who were exposed to IEDs. CTE occurs in a relatively slow progression and signs can begin to appear years after the trauma. Scientists do not currently know why some people with similar histories of head trauma develop CTE and others do not. The photo above shows the contrast between a healthy brain and the degeneration that found in the brain of someone with CTE. https://www.mayoclinic.org/diseases-conditions/chronic-traumatic-encephalopathy/symptoms-causes/syc-20370921

Diagnosis of Concussion

Concussion diagnoses typically rely on neurological and cognitive testing. A neurological test involves tests of vision, hearing, and balance for any deficits that may have been caused by brain trauma. Cognitive tests typically involve tests of memory and concentration that are typically impaired by a concussion. https://www.mayoclinic.org/diseases-conditions/concussion/diagnosis-treatment/drc-20355600 Brain imaging can be used for cases where severe trauma has occurred to assess the level of damage. Two methods that can be used are functional Magnetic Resonance Imaging (fMRI) and Diffusion Tensor Imaging (DTI). fMRI can help detect areas in the brain that have been damaged by concussion and the extent of that damage. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995073/ One effect of concussions is damage to axons. DTI can determine where the axonal damage has occurred through abnormal levels of diffusion of water throughout the brain. https://www.mdedge.com/neurology/article/76185/traumatic-brain-injury/dti-may-detect-axonal-injury-after-sports-related The image is a simplified version of a DTI scan. The areas in red indicate where there has been damage to the axons and the areas in blue indicate where diffusion levels are higher than normal which suggests those areas are compensating for the damage. https://medicalxpress.com/news/2016-06-concussion-outcome-advanced-imaging.html

Prevention of Concussion

The detrimental effects of concussion have led to efforts to prevent concussions. One arena where many prevention efforts have been focused is on athletics. Improvements have been made to helmets to help them cushion the head from blows. Another important area has been a focus on delaying when children are allowed to start using increasingly violent maneuvers in athletics. The age when kids can start tackle football or when soccer players can head a ball has been pushed later in an effort to delay concussion injuries. Another focus has been on proper training for these maneuvers. Serious injuries often happen when a maneuver is done incorrectly and teaching kids when and how to use them correctly can help lessen injuries without changing the sport.

Underlying Pathways in Schizophrenia

Development of Schizophrenia

There is no definite cause of schizophrenia. Most studies point to issues during pregnancy including genetics, abnormal brain development, infection during pregnancy, and complications during birth. Some studies suggest head injuries, stressful life events, and social isolation. https://www.steadyhealth.com/articles/schizophrenia-development Patients with schizophrenia show delays in milestones as children which suggests that development of schizophrenia develops much earlier than the timing of the onset of schizophrenic symptoms. https://onlinelibrary.wiley.com/doi/abs/10.1111/cge.12111

Current Drug Treatments

            The most commonly used treatment is antipsychotic drugs that block dopamine receptors. There are issues with these medications however, they tend to present serious adverse side effects such as lightheadedness and blurred vision. They can also cause tardive dyskinesia, which is characterized by involuntary, repetitive movements. https://www.mayoclinic.org/diseases-conditions/schizophrenia/diagnosis-treatment/drc-20354449 Lithium is also used as a treatment for schizophrenia in conjunction with other drugs but is more commonly used for the treatment of bipolar disorder. It seems to work through the inhibition of GSK. https://onlinelibrary.wiley.com/doi/abs/10.1111/cge.12111

The Wnt Pathway

            https://youtu.be/NGVP4J9jpgs This video gives a great overview of how the Wnt pathway works. The Wnt pathway has been implicated in schizophrenia. The antipsychotics mentioned earlier act on dopamine. The dopamine pathway ties into Wnt signaling through GSK3 which is decreased by the decrease of activation of dopamine receptors. https://onlinelibrary.wiley.com/doi/abs/10.1111/cge.12111

Lithium seems to work in a similar fashion. Lithium competes with magnesium and inhibits GSK3. There is also some evidence that lithium destabilizes the destruction complex mentioned in the video that exists when the Wnt pathway is off. This activates the Wnt pathway and helps to regulate some of the symptoms seen in both bipolar disorder and schizophrenia. https://onlinelibrary.wiley.com/doi/abs/10.1111/cge.12111

The Role of Genetics

            Schizophrenia is fairly rare in the general population, occurring in about 1% of people. However, it occurs in 10% of people who have a close family member with schizophrenia. This leads to the assumption that there are genetic factors at play. https://www.nih.gov/news-events/nih-research-matters/mutated-genes-schizophrenia-map-brain-networks Researchers have found that spontaneous mutations, that are not inherited from either parent play a role in schizophrenia development. Some of these mutations cause an increase in activity of GSK3 and a decrease in Wnt signaling. Mutations that are linked to schizophrenia all appear in the prefrontal cortex which is related to executive functioning in the brain.

https://sbarnum.weebly.com/

Other studies have found that there are mutations in deleted genes that are passed down from parents. Genetic mutations can cause unnecessary pruning of communications in the brains of teenagers who will later experience schizophrenic symptoms. Normally pruning in the brain is a good thing and gets rid of unnecessary connections within the brain as shown in the picture above. However, this goes wrong in schizophrenia. A gene known as C4 seems to be the culprit. C4 is responsible for tagging synapses for pruning, in schizophrenia it is overactive and causes too much pruning. https://www.nih.gov/news-events/news-releases/schizophrenias-strongest-known-genetic-risk-deconstructed

Schizophrenia and Bipolar

Earlier I mentioned that GSK3 seems to be have an effect on both schizophrenia and bipolar disorder. In schizophrenia elevated GSK3 affects brain development through deficits in the corpus callosum (connections between brain hemispheres) and connections to the thalamus which acts as the relay station for brain signals. There is evidence that in adults, elevated GSK3 interferes with microtubules which allow signals to be transmitted through the brain. https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(07)00035-5

Bipolar disorder also has an increase in GSK3 activity. The difference is what it does in the brain. The evidence suggests that the main action of GSK3 in bipolar disorder is apoptosis activity (cell death). This leads to smaller brain volume and the loss of neurons in areas of the brain that are related to the regulation of emotions. This relates to the extreme manic and depressive symptoms and quick switches between the two seen in bipolar disorder. https://www.sciencedirect.com/science/article/pii/S0149763407000243

Conclusion

An increase in GSK3 and decrease in Wnt signaling presents a new target for the treatment of both schizophrenia and bipolar disorder. The regulation of the Wnt pathway could allow for a treatment without the adverse effects of antipsychotic treatments. Genetic factors play a role in the development of schizophrenia that have not been fully discovered but some seem to directly affect Wnt signaling.

A Complex Story of Autism

Artstract created by T. Courier

Autism Characteristics

https://www.autismspectrumexplained.com/characteristics-for-kids.html

The current Diagnostic and Statistical Manual categorizes Autism as a spectrum. The benefit of using a spectrum model is it allows for differences in how it manifests including what symptoms exist and how severe they are. Some possible symptoms of Autism Spectrum Disorder (ASD) are social impairments, communication difficulties, repetitive movements, and obsessive interests. ASD is more common in boys and can be found in 1 out of 68 children. ASD is a disorder that is highly heritable and there are many genetic disorders that are linked to the development of ASD. There is still a lot that we do not know about ASD and no cure currently exists. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Autism-Spectrum-Disorder-Fact-Sheet

Related Disorders

There are a number of genetic disorders that are related to ASD. One of these disorders is Fragile X Syndrome. Fragile X Syndrome occurs when there is a mutation on a gene (FMR1) that makes a protein (FMRP). This mutation means that FMRP is not formed. FMRP has a crucial role in regulating the translation of mRNA and can inhibit long term depression at the synapse. Long term depression occurs at the synapse when connections weaken and are pruned when they are no longer needed. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722574/ The lack of FMRP can lead to an increase in immature dendritic spines which is characteristic of both Fragile X and ASD. There is significant symptom overlap between Fragile X and ASD and many people with Fragile X also have ASD. This makes Fragile X and the issues caused by a lack of FMRP a useful target to try to understand ASD. https://www.cdc.gov/ncbddd/fxs/facts.htm https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4024105

What is Happening in the ASD Brain?

Many of the genes that are involved with the development of ASD involve the glutamate pathway. The glutamate pathway is involved with the strength of synapses and when a lot of glutamate is present synapses are strengthened. https://flowpsychology.com/long-term-potentiation-definition-psychology/ The other important part of this process is that synapses that are not needed are pruned. However, in ASD this pruning does not happen. This may be due to overactive mTOR signaling. Autophagy is used to break down components of unneeded synapses. This process is inhibited by an overactivation of mTOR. The photo above shows the underdevelopment of a brain of a child with ASD and the lack of synaptic connection strength. The pruning that happens normally in childhood and adolescence is believed to allow for the rise of executive cognitive functioning, reasoning, and abstract thought. Many of these abilities are not present in people with ASD. Treatment with mTOR blockers may seem like an easy solution to rescue some of the cognitive deficits that are seen in ASD. Unfortunately, it is not that easy, mTOR signaling occurs throughout most of the body and cannot be target to only the areas that are affected by ASD. https://www.cell.com/action/showPdf?pii=S0896-6273%2814%2900651-5

Treatment Options

Further research is taking place to determine how mTOR can be targeted without causing damaging effects to other parts of the body. There are some treatments that currently exist for ASD. Early intervention treatments are helpful when a person is diagnosed with ASD as a young child. These treatments are focused on helping the child reach developmental milestones. Behavioral interventions can be used to reduce repetitive behaviors and to increase social skills. Sensory integration therapy can also be useful for people with ASD who are easily overwhelmed by sensory stimuli. Dietary interventions and supplements may also be necessary because many people with ASD experience gastrointestinal issues and others may refuse to eat certain types of food and miss out on necessary nutrients. Current treatments are focused on reducing the more severe symptoms of ASD and increasing social and life skills. https://www.cdc.gov/ncbddd/autism/treatment.html

The Ugly Truth of Addiction

 

What is Addiction?

Addiction is a psychology and physical inability to stop consuming a drug, activity or substance, despite it causing physical and psychological harm. People can be addicted to a number of different things, but I would like to focus on drug addiction. Addiction manifests itself in physical and psychological symptoms. Tolerance is related to physical addictions. Tolerance occurs when the body begins to get used to the drug of abuse and effects of the drug are not as strong as they once were. This is why drug users will say that they never reach the level of their first high again.

Psychological addiction manifests in withdrawals and cravings. Withdrawal has physical symptoms including agitation, insomnia, muscle tension, and vomiting. The underlying cause of withdrawal is psychological. Tolerance makes the body dependent on drug use to achieve normal levels of neurotransmitters. When that drug is not used, levels are much lower than they would normally be, leading to physical symptoms. Cravings are the body’s desire for the drug. This leads to desire to use the drug again and is the major culprit in relapse. https://emeraldcoastjourneypure.com/physical-vs-psychological-addiction/

Hijacking the Reward System

            Drugs of addiction directly or indirectly affect levels of dopamine in the brain. The reward pathway in the brain relies on dopaminergic projections between two brain areas, known as the nucleus accumbens and the ventral tegmental area. Shown in the photo on the left. In normal circumstances this is good. The reward pathway allows us to feel good when we eat, drink, or have sex. Drugs of abuse also trigger this pathway by increasing the amount of available dopamine through inhibiting reuptake or enhancing release into the synapse. That is why drug use feels good. This is also why people who are trying to quit using drugs feel so awful during this experience because their body has started to produce less dopamine to compensate for the boost from the drug use. This means that when that boost isn’t happening things that should be naturally reinforcing aren’t. https://www.sciencedirect.com/science/article/pii/S0092867415009629

https://forensicpsychologist.blogspot.com/

 

Addiction and Learning

Synaptic plasticity is of crucial importance to normal brain function. Synaptic plasticity is the brain’s way of strengthening connections that are used frequently and getting rid of ones that are no longer needed, like the plot of the book you were forced to read in fifth grade. The following video does a good job of explaining what is going on in the brain during synaptic plasticity.

As mentioned earlier, drugs of abuse cause an increase of dopamine at the synapse. This excess dopamine. One of the receptors that dopamine binds to causes AMPA receptors to allow more glutamate in or can stimulate the release of more glutamate into the synapse. This means that more LTP takes place.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280337

https://schoolbag.info/biology/living/230.html

The graphic above gives a good representation of what happens in the brain when drug addiction occurs. Two things happen when in regards to synaptic plasticity when drug use occurs. One is that initial drug use causes a strengthening of the connection between the drug use and the reward pathway. After continued drug use, AMPA receptors are removed from the synapse. This means more drug use is needed to achieve the same amount of stimulation that exists in someone who has never used drugs. The brain knows there is a connection between the use of the drug and an increase in dopamine and glutamate levels and this can lead to drug-seeking behaviors.

A Glimmer of Hope: Addiction Treatment

Addiction changes connections in the brain. This shows why it can be so hard for people to quit. The bright side is that there are a lot of treatment options out there for people who want to quit.

Medications can be used but are typically used in conjunction with another treatment option. The medications are meant to make the transition off drugs easier. They can curb some of the cravings which make people less likely to relapse. They can also curb some of the nasty symptoms that come with withdrawal. Medications are also helpful when people have a co-occurring mental illness that the drugs were being used to manage the symptoms of.

Therapy can also be used to treat addiction and can happen in either an inpatient or outpatient setting. Therapies are meant to change thoughts about drug use and increase life skills, such as coping. Therapy can also be used to treat co-occurring mental health conditions. Therapy can be used successfully in maintaining sobriety.

https://www.drugabuse.gov/publications/drugfacts/treatment-approaches-drug-addiction

 

Memories and Stress

What is PTSD?

PTSD is post-traumatic stress disorder. It is characterized by a number of symptoms that follow a traumatic event in someone’s life. PTSD symptoms are organized into four clusters: re-experiencing, avoidance, arousal and reactivity, and cognition and mood. An example of re-experiencing symptoms would be nightmares or flashbacks of the event. Avoidance symptoms involve staying away from places or people who are reminders of the event. Arousal and reactivity symptoms include angry outbursts and hypervigilance. Mood and cognition symptoms include negative thoughts about oneself and a distorted sense of guilt. It is interesting to note that of all the people who experience trauma that would fit the diagnostic criteria for PTSD, only about 10-20% actually develop it.

https://www.nimh.nih.gov/health/topics/post-traumatic-stress-disorder-ptsd/index.shtml

Animal Models for Anxiety

https://www.acsh.org/news/2017/11/20/how-mice-help-discover-new-anti-depressants-12171

When studying the effects of stressful situations, animal models are typically used. A research article by Reul focused on the use of commonly used mouse models and stress paradigms. One common paradigm is known as the forced-swim test. The photo above is a depiction of what a forced swim test looks like. In this test a mouse is placed in a container of water with sides that are high enough that it is unable to escape. Eventually the mouse will no longer try to escape or swim and will just float in the water until it is removed. Even in this stressful situation, the mouse will remember that it has no means of escape from the container and on a repeated trial will spend less time trying to escape. This particular test has shown itself useful for the testing of antidepressants. An effective antidepressant will prolong the amount of time that the mouse spends looking for an escape. This also allows us to look out how the brain changes when we make memories under stressful circumstances.

Epigenetics

https://www.youtube.com/watch?v=g12kIu9jrIk

The linked video does a fantastic job of explaining what epigenetics are. How does that relate to PTSD and anxiety? One thing that can cause epigenetic changes is environmental stress. The environmental stress can be the traumatic experience that leads to PTSD. Stress causes the release of hormones known as glucocorticoids. Glucocorticoids can affect cellular functioning and when their levels are elevated long term it can have detrimental health effects. The particular area of interest in epigenetic changes associated with PTSD is the hippocampus. The hippocampus is the part of the brain that is crucial for the formation of memories. Changes here can lead to loss of memory functioning.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2891396/

The Dentate Gyrus

https://www.ccn.ucla.edu/wiki/index.php/Unfolding

The dentate gyrus is a small portion of the hippocampus that receives sensory information that has gone to another part of the brain first. This means that it is not receiving raw information, but rather information that has been partially processed. The figure above is a view of the hippocampus that shows where the dentate gyrus is located. The dentate gyrus plays a role in the formation of memories but is also important for pattern separation. Pattern separation occurs when, for example, a red pen and a blue marker activate different responses in the brain. The dentate gyrus is responsible for making the representations of those two different things in the brain more different. What research has found is that the hippocampus and dentate gyrus is smaller in people with PTSD. This could be leading to a lack of pattern separation that makes something that was not associated with trauma cause fear because it cannot be distinguished from another thing that was associated with trauma.

https://www.research.va.gov/pubs/docs/va_factsheets/ptsd.pdf

Benefits of Exercise

It has been said a hundred times that exercise has huge benefits for your health. One mental health benefit is that exercise has been shown to reduce anxiety. Exercise has been used in conjunction with therapy to alleviate symptoms for people who have been diagnosed with anxiety disorders. Exercise should not be overlooked as a way to relieve anxiety that is so common in many of our daily lives.

https://adaa.org/living-with-anxiety/managing-anxiety/exercise-stress-and-anxiety

Relationship between Alzheimer’s and Type 2 Diabetes

 

https://www.researchgate.net/figure/Insulin-signaling-linking-Type-II-diabetes-and-Alzheimers-disease-Alterations-in_fig4_323247347

Research has consistently found that there is a link between Type 2 Diabetes and Alzheimer’s Disease. People with one condition are more likely to develop one disease if they already have the other. What is happening here? A recent article by Vieira, Lima-Filho, and Felice advances the role of insulin resistance in Alzheimer’s Disease

https://www.ncbi.nlm.nih.gov/pubmed/29129775

What is Type 2 Diabetes?

 

https://www.thermofisher.com/blog/proteomics/type-2-diabetes-metabolomics-reveals-lipid-dysregulation/

Type 2 Diabetes is characterized by insulin resistance in the body. When food is eaten, it is broken into glucose and enters the bloodstream. Insulin is released from the pancreas in response to glucose entering the bloodstream. Insulin’s job is to help cells absorb and use glucose. In Type 2 Diabetes, the cells become resistant to insulin and can no longer use the glucose in the body. This causes elevated blood sugar levels and starves the body’s cells of glucose. The figure above is a graphic representation of insulin resistance.

https://www.cdc.gov/diabetes/basics/type2.html

What is Alzheimer’s Disease?

https://ghr.nlm.nih.gov/condition/alzheimer-disease

Alzheimer’s is a neurodegenerative disease that causes a loss of cognitive function. The figure above shows a comparison of a healthy brain to the losses sustained through Alzheimer’s Disease. The two characteristic features of Alzheimer’s Disease are a buildup of neurofibrillary tangles and amyloid plaques. Amyloid plaques are formed when a larger protein is cleaved to form amyloid-beta. One potential form of this smaller protein, AB42, is harmful to the brain. In normal brains, AB42 is formed in relatively small amounts and can be cleared. In Alzheimer’s this process does not occur and amyloid-beta builds up and forms plaques in the brain. Neurofibrillary tangles occur when proteins known as tau begin to misfunction. In healthy brains, tau is a part of the microtubule system in cells that acts like a railroad system in the cell. In Alzheimer’s, tau detaches from the microtubules and builds up in the brain and disrupts functioning.

https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease

Insulin Resistance in Alzheimer’s

The article mentioned at the beginning of my post investigated the role of insulin resistance in Alzheimer’s Disease. Researchers have found that insulin resistance appears to occur in the brain in the case of Alzheimer’s. As I mentioned, insulin resistance causes cells to starve because they cannot use the glucose that is in the bloodstream. The existence of this phenomenon in the brain can cause the death of neurons in the brain because they are not receiving proper nutrients. It would be irresponsible to suggest this as the absolute cause of Alzheimer’s. As a result, below I outline some other mechanisms and potential causes recognized in current research.

The Role of Inflammation

Inflammation occurs as an immune system response. In the brain, the cells that act as a part of the immune system are microglia. The microglia make attempts to clear the amyloid plaques that have built up, but for reasons that are still debated are unable to. This can be harmful to the brain because microglia can inadvertently harm healthy cells within the brain when they try to eliminate amyloid plaques. This can contribute to cell death within the brain

Chronic Inflammation in Alzheimer’s Disease

Endoplasmic Reticulum Stress

The endoplasmic reticulum is an organelle that is responsible for folding proteins. This is important because the amyloid-beta protein that is made within the brain travels to the endoplasmic reticulum to be folded. The endoplasmic reticulum is very sensitive to changes in the cell’s natural state and will not function properly when under stress. This means that the amyloid-beta protein is likely to be misfolded and contribute to the amyloid plaques. It is currently unclear what causes endoplasmic reticulum stress, some possible factors could be the existing disease pathology, inflammation, or aging.

https://royalsocietypublishing.org/doi/full/10.1098/rsob.180024

Conclusion

There appears to be a strong link between Alzheimer’s and Type 2 Diabetes. This potentially leads back to Alzheimer’s Disease involving insulin resistance in the brain. There are a lot of other factors at play in the development of Alzheimer’s, including inflammation responses and cellular stress. Continued research will hopefully answer some questions but will likely bring in more questions about why some people develop Alzheimer’s Disease.

WHACK: Concussions and Neurometabolism

Concussions are a growing concern in athletics as we learn more about the consequences of multiple concussions and long-term dangers. Not only are large traumatic concussions of concern, mild traumatic brain injuries (TBI) that occur repetitively can also be damaging.

After the trauma of a concussion, the cell membrane is disrupted from stretching and increases the permeability of ions across the membrane. Large amounts of sodium and calcium enter the cell while potassium leaves the cell. Typically, sodium enters the cell for depolarization and potassium exits the cell only to re-establish the resting potential after depolarization. The flux of ions therefore, induces spontaneous depolarization of neurons.

Potassium levels are quickly re-establishing by potassium pumps. However, potassium pumps require energy from the hydrolysis of ATP to move potassium back into the cell. This requires a lot of ATP. Cells produce ATP through glycolysis in the mitochondria. Glycolysis uses sugars such as glucose to produce ATP, reducing power and pyruvate. Under normal conditions, pyruvate is converted to acetyl-coa and enters the citric acid cycle to produce further reducing power. The reducing power is used in the electron transport chain to produce large quantities of ATP. If glycolysis goes into overdrive, the pyruvate will be converted to lactate which is highly inefficient for ATP production. This hyperglycolysis depletes energy stores quickly and is unsustainable for the cell. Additionally, lactate can cause neuronal dysfunction, changes in blood brain barrier permeability, and brain inflammation, which are all associated with long-term damage triggered by concussions.

Neurometabolic Cascade after Concussion

This period of hyperglycolysis lasts about 24 hours before the polar opposite process occurs. For this part of the story calcium is the star and villain. To combat high levels of calcium, the cell sequesters calcium in the mitochondria. However, the stress of sequestering calcium leads to the increase in reactive oxygen species (ROS) that typically act as signaling molecules. ROS impairs the mitochondria’s ability to perform glycolysis, which causes hypoglycolysis. As a result, the cell is in an extreme low energy state. During the period of hypoglycolysis, working memory is impaired. This phase will last between two and four weeks depending on the individual.

Neurometabolism gradually returns to normal, alleviating many of the symptoms. However, this can be deceiving because the brain is often inflamed for up to a year after the trauma. Though not completely understood, the event of repeated concussions can have long-term implications for individuals, such as the development of chronic traumatic encephalopathy (CTE) which is similar to Alzheimer’s and Parkinson’s.

The most vulnerable time for a repeated concussion is during the recovery period of a concussion. If a second concussion occurs while the cell is in hypoglycolysis, it is hypothesized that neurons cannot combat the extreme efflux of potassium as ATP in the cell is depleted. Therefore, it is common protocol to prohibit individuals with concussions to partake in activities that risk another concussion. A challenge is that recovery time differs greatly between individuals which makes it difficult to ascertain when the individual has recovered. More research in the indicators of concussions and the recovery thereof are essential to properly treat concussions and mild TBIs.

BrainSTORMing to understand Autism Spectrum Disorder… and Rain Man

Rain Man, a breakthrough Hollywood film from the late eighties, brought us a representation of a man with autism. The film enabled us to better understand how one specific individual with autism perceives the world. We as a society can do better at giving individuals with autism the necessary resources to allow for them to have the comfort and safety in their everyday lives.

While this film brought autism to the public attention, we must be careful at what we take away from this film. We must not walk away from this film with the impression that all individuals with autism are savants, as Oscar winning actor Dustin Hoffman displayed in his portrayal of Raymond Babbitt. We must realize that autism falls under the umbrella term, autism spectrum disorder (ASD) and that individuals with ASD can express many different symptoms and behaviors.

 

The symptoms and behaviors that correspond with ASD affect each individual differently on how they understand and react to the world around them. No two people are affected in the exact same way.

“If you’ve seen ONE child with autism, you’ve seen ONE child with autism.”

There are many questions to why this statement is true. However, research has been done to help explain the complexity of the vast array of symptoms and behaviors.

 

GENETIC FACTORS

 There are a number of factors that can influence the development of ASD including genetics. Genetic mutations can be visible in many different proteins and genes such as SHANK, UBE3A, MECP2, and TSC1-TSC2. Increased risk of these mutations may also be due to environmental reasons, complications during pregnancy, or older aged parents.

 

SHANK

Genes encoding for the SHANK protein are seen in individuals with ASD. These proteins are known as scaffolding proteins, which function in synapse morphology. When this protein is mutated, which has been performed in animal studies, various symptoms and behaviors that fall under ASD are observed. Motor behavior and social interaction is most noticeably affected.

 

UBE3A 

UBE3A is a gene that is essential for neuronal growth and codes for an enzyme that breaks down other proteins within the cell. In ASD, this gene has been noticed to be mutated or deleted. Without this gene, an important protein known as ARC continues to be made. The ARC protein weakens the synapse by removing AMPA receptors. AMPA receptors are integral to plasticity and synaptic transmission. A weakened synapse leads to ASD related symptoms.

 

MECP2 

MECP2 acts a transcription repressor and is involved in ensuring that DNA is folded into chromatin properly. When this gene is mutated, DNA is not folded properly causing an imbalance between inhibition and excitation. Too much or too little MECP2 protein leads to ASD symptoms.

 

TSC1-TSC2 

TSC1-TSC2 are proteins that work closely with growth factors such as brain derived neurotropic factor (BDNF). When these proteins are activated a, GTPase activating protein (GAP) is reduced leading to a cascade of proteins being activated. Rheb is activated, followed by mTOR. When TSC1-TSC2 proteins are mutated, the activation cascade is disrupted leading to abnormal protein synthesis and ASD symptoms.

 

These genetic factors are just some of the reasons for the vast array of symptoms and behaviors associated with ASD. The effects of all disorders under the umbrella term are unpredictable and wide ranging. On top of that, many of it is not completely understood.

 

The umbrella has continued to expand. As more research continues to be done, the umbrella will most likely continue to expand. Whether you think it is right to have a broader spectrum or not, we can all take more time to brainstorm and educate ourselves on what falls under the umbrella.

 

The film, Rain Man, successfully brought massive public awareness towards one specific autism spectrum disorder. It is up to us, however, to maintain a momentum of interest and action so that efforts in understanding ASD and treating the disorders under the umbrella can continue to improve.

 

To follow the research summarized above, follow:

https://www.nature.com/articles/nature11860

To continue your education on ASD, follow:

https://www.mayoclinic.org/diseases-conditions/autism-spectrum-disorder/symptoms-causes/syc-20352928

Just Because We Can, Should We?

Austism spectrum disorder (ASD) includes a large range of conditions that is characterized by difficulties with social skills, communication, and repetitive behaviors. As of right now, there is no cure for ASD, and the current treatments include behavioral management therapy, medication treatments, nutritional therapy, and more.

Since ASD is largely a genetic disorder, it is justified to presume any effective cure would be based in gene altering practices. However, with gene altering technology comes things such as protecting and securing DNA data bases and each family’s confidentiality. The most controversial of all considerations might be the abuse of further research of gene altering technology to moving into the realm of eugenics, which is controlled breeding by choosing favorable genetic traits. This begs the question, should we knowingly alter the genes of an unborn child because those genes might lead to ASD?

The Debate

Many believe a cure should be pursued. Those suffering from or supporting those that suffer from the more severely debilitating symptoms of ASD have seen the worst of what the disorder can bring: extreme difficulty with sleeping, focusing, communication, and much more. Those advocating for a cure might not see ASD as being an integral part of who someone is but more of a chain holding someone back from living a fulfilling life.

But of course, not everyone on the spectrum suffers from severe symptoms. Many that have experience with the less severe symptoms advocate that a cure is an unethical pursuit. They believe that by pursuing a cure for autism it would lead to completely and irrevocably changing a person, and there is no justifiable reason to do so.

A Slippery but Useful Slope

The pursuit of a cure would undoubtedly lead to major advancements in understanding the human genome with hopefully having the ability to know exactly what genes cause ASD and why. But the case made here is if a cure is pursued, one must be deliberate and proactive in their research.

This is to say, with the knowledge of how to alter gene expression ultimately comes the ability to change genes whether or not they are harmful, so preventative laws or policies to avoid the use of eugenics must be enforced. Pursuing scientific advances isn’t always ethical, and in the case of gene altering technology, crossing the line can be far too easy and appealing. (If you want to read more about the ethics of gene altering technology, click here.)

Freedom is Key

Ultimately, the choice of whether to change a child’s genome before they are born to prevent ASD would be left up to the parents. If this were to ever become a reality, it should never be forced upon a parent given the sheer lack of knowledge of how ASD would affect the child in the future.

The Science

As mentioned before, ASD is predominantly a genetic disorder. Furthermore, the implicated causes for ASD are genetic in nature.  A mutation in the following proteins are linked to certain forms of ASD:

  • L-VSCC in Timothy syndrome
  • RSK2 in Coffin-Lowry syndrome
  • CBP in Rubinstein-Taybi syndrome
  • Ube3A in Angelman syndrome
  • MECP2 in Rett syndrome

 

Additionally, strong evidence has linked mutations of neuroligin and neurexin synaptic adhesion molecules to ASD. Neuroligin and neurexin work together to modulate the formation and function of synapses. For example, neuroligin-3 ASD missense mutations in knock-in mice showed similar characteristics known to ASD.

Another example of a gene mutation linked to ASD is the mutation of the FMR1 gene that causes Fragile X Syndrome, which leads to the decreased expression of the protein FMRP, which regulates the translation of certain mRNAs at the synapse.

Autism: a Disorder to Cure or a Personality Change to Accept

Autism Spectrum Disorder is characterized by presence of particular symptoms explained by certain DSM-5 criteria.  To summarize, the disorder is characterized by problems with social functioning across multiple contexts, repetitive or restrictive behavior, presence in early development, impairment that is significantly different than normal, and exclusion of any other intellectual disability to better explain the symptoms a person experiences.  In addition to this, the DSM characterizes the disease based on severity.  These levels can largely impact what kind of treatments are desired or available.  Level 1 “requiring support” is characterized by inflexibility that significantly impairs ability to switch between activities, and organize or plan for future events.  Level 2 “requiring substantial support” is characterized by behavior inflexibility, difficulty coping with change, or other repetitive and restrictive behaviors.  These impairments are obvious, even to a casual observer.  Communication skills (both verbal and non-verbal) are significantly impaired and social interaction is limited.  Level 3 “requiring very substantial support” is often referred to as severe autism.  People with this level of disorder experience severe distress when attempting to transition to new activities or thoughts.  They also suffer with lack of flexibility in behavior but this inflexibility interferes with all contexts.  Coping with change is severely compromised and social interactions are rarely sought out.  When social interaction is sought out, attempts are made in inappropriate or unusual ways.  Despite knowledge of the genetic component, little is known about the exact mechanism that causes autism.  New research suggests a pathway as well as possible drug treatments for the disorder.

Neurological Underpinnings

In a normally functioning brain, release of a chemical called glutamate leads to opening of certain channels that allow movement between adjacent cells and extracellular fluid.  This movement leads to ion flux which activates a variety of downstream effects through modification of transcription.  Transcription is a vital aspect of DNA replication that leads to genes being read and used properly.  In ASD, Calcium channels are open too much leading to excess Calcium entering the cell and changes in transcription.  Genetic information is then read improperly, leading to the behavior we characterize as Autism.  One possible genetic predictor of ASD is SHANK protein.  SHANK proteins are separated into several different categories, but SHANK 2 and SHANK 3 are best understood in term of ASD.  SHANK 3 is largely responsible for social interaction deficits and repetitive behaviors while SHANK 2 is largely responsible for abnormal motor behavior and problems with vocalization and socialization.  Identification of these has pharmaceutical impacts.  A drug that partially blocks a certain kind of receptor and a drug that activates a gene that regulates ion flux have been shown to decrease behaviors commonly associated with autism.  These studies have been done on mice, but these drugs shed light on potential interventions to cure the underlying mechanisms of Autism Spectrum disorder.

Community

Vital to human existence is our ability to relate to those around us.  We crave connection and relation and when we feel misunderstood, we feel isolated and alone.  In these times, we reach out to anyone we can.  For many families living with autism, reaching out has turned into so much more. Parents of children with ASD often form community forums and support groups.  These pages aim to educate other parents and share useful resources for parenting children diagnosed with Autism Spectrum Disorder.

One argument against “curing” autism is that people with autism are a part of a certain community due to their disability.  This is similar to people who experience deafness and have the opportunity to use a cochlear implant.  At first glance it seems like an amazing opportunity: for the first time a person can hear their own voice or the voice of a loved one.  There are countless heartwarming videos when a child hears their parent’s voice for the first time, but there is so much more to the journey.  The brain has to develop new pathways to accomodate this new sensation.  This new sensation can be overwhelming and challenging to deal with.  In addition, this person no longer relates to the deaf community as they once did.  They no longer have a support system who fully understands what they are going through.  This is similar to the experience people with autism would have if they were “cured.”  They no longer would have a community that fully understands what they’re going through.

Hidden Beauty

Creating a cure for a disease on a surface level sounds like something we couldn’t argue against.  In this case, it’s a little more complex.  Some people with autism feel a sense of freedom through their diagnosis while others are burdened by their social exclusion and inflexibility.  Despite this, there is a sense of beauty in something so unique.  Underneath the repetitive behavior, anxiety, and self injury is often a passion deeper than what is expected.  People with severe autism aren’t impacted by the world the way people without are.  The role they play is not defined by the success they have in traditional endeavors like careers and families.  Instead, success is defined by the little things: ability to interact with others, sitting, sleeping, playing.  Celebration is prolonged and exciting.  Anyone who has worked with people with disabilities can tell you just how rewarding it can be.  It’s the little things like teaching a child with autism how to make mac and cheese.  It was such a little event, but the sense of pride he developed from doing something completely on his own was like nothing I’d ever seen before, and it changed the way I see the world.  Every little victory means so much more.  Whether you believe in a cure, acceptance, or a little bit of both Autism Spectrum Disorder is so much more than what first meets the eye.

Spam prevention powered by Akismet