Cobbers on the Brain

A couple of weeks ago I was talking to my parents and they asked me about classes and how they were going. I began to tell them about what I’m studying and began to talk a bit about neurochemistry. I told them about how we read an article each week and really break it down in order to fully understand what the article is talking about. I told them about how we’ve talked about insulin, dopamine and even endocannabinoids. Jokingly, my dad immediately asked,
“Endocannabinoids? You’re not going to start smoking pot are you?”
Although I know my dad was only kidding, his quick response when I said I was learning about endocannabinoids was not surprising. Although marijuana is associated with sitting on the coach, playing video games and raiding the house for food, there are enormous benefits to the drug that it seems few recognize, or at least take seriously. Cannabis has become an increasingly popular topic in today’s society, especially since there are states that have begun to legalize it for medicinal use, and for good reason.
I’m sure many of you have heard of THC, the main psychoactive ingredient in marijuana. But what I do not believe many know is that our bodies create similar molecules known as endocannabinoids. The two most important are anandamide (AEA) and N-arachidonoyldopamine (2-AG). These endocannabinoids do not have the same psychoactive effects, but do have very positive influences on our bodies.
The endocannabinoid pathway is very unique because it works backwards. Other pathways work from a pre-synaptic cell (cell sending the signal) to the post-synaptic cell (cell receiving the signal). The endocannabinoid pathway works instead from post-synaptic to pre-synaptic. This process is called retrograde signaling. Retrograde signaling is a feedback mechanism used to regulate chemical neurotransmission.
Manipulation of the cannabinoid pathway may provide treatment for those suffering from Alzheimer’s disease (AD). Cannabinoids have been seen to reduce oxidative stress, neuroinflammation and apoptosis (cell death) that are evoked by β-amyloid, which is involved in AD. Cannabinoids also may have the ability to promote repair mechanisms within the brain. Manipulating the endocannabinoid system in AD patients may offer a better substitute for current treatments that often have unwanted side effects such as liver damage and gastrointestinal disturbances.
More and more people are becoming aware of the positive effects of marijuana. But the main issue for many is its psychoactive side effects. Now researchers are working on ways to extract THC and use it in clinical trials. Scientists are also working on ways to decrease those psychoactive side effects in order to provide a more ethical way to administer treatment with the use of cannabinoids.
I understand why it is so difficult to accept that marijuana is good for you, especially with its psychoactive effects and the stigma that has been pressed upon it. However, with new methods of research and the vast amount of information there is out there, it is hard to ignore the facts. There is little evidence that smoking weed is bad for you. In fact, there is more evidence that consuming alcohol is more detrimental to our brains than getting high!
Now, I don’t mean that we should all start getting high while listening to the newest Arctic Monkeys album, but rather to open our minds to the reality that Cannabis can be good for the body. It can be beneficial for those suffering from Alzheimer’s, Multiple Sclerosis, severe pain, Tourette’s syndrome, seizures, migraines; the list goes on and on. Hopefully, as time proceeds others will begin to recognize its benefits, and work to focus on finding a way to harness its helpful properties.

Parkinson’s disease (PD) is a degenerative disease of the central nervous system that affect an estimated one million individuals in the united states. It has extremely visible characteristics such as uncontrollable shaking, rigidity, and impaired motor skills. PD is primarily a result of the death of dopamine producing cells in the brain. A protein called alpha-synuclin that normally mediates cell death is disrupted and leads to Lewey body formation in the brain.
There are several current treatments that attempt to counteract the effects exhibited by an individual with PD, but none fully rid the individual of the disease. The role of iron homeostasis in the brain in relation to the development to Parkinson’s disease has been under more and more investigation in recent studies of the disease.
Iron is carefully regulated in the brain and the imbalance of iron can lead to very disruptive consequences the central nervous system. Specifically, the role of iron chelators have been examined as a potential treatment for PD. Iron chelators work to bind iron and remove them from your system. A patient with PD exhibits elevated accumulation of alpha-synuclin as well as increased oxidative stress. Oxidative stress greatly contributes to mitochondrial dysfunction and neuronal death. These iron chelators have been found to inhibit these harmful processes from occurring. In particular, a drug named M30 is being studied as a potential treatment for PD. However, you can find sources of iron chelators in naturally occurring substances as well, such as green tea. Epigallocatechin gallate (EGCG) is abundant in green tea can help alleviate problems caused by increased iron overload as well as acting as an effective antioxidant to deal with the oxidative stress caused by PD.
Although there is no one-stop-cure-all method to preventing or treating Parkinson’s disease, there are things we know about the pathology that may provide useful insight in helping prevent the disease. The accumulation of iron and the resulting oxidative stress in your cells has been shown to contribute to PD. So taking healthy supplements that have antioxidative characteristics is extremely healthy (antioxidants play a role in a variety of diseases), as well as watching your iron intake and being mindful of what you’re ingesting into your body. Time and time again, diet seems to play a crucial role in our health and the prevention of a variety of different diseases.

If there is one thing I’ve learned after reading scientific articles it is that there is always something more I need to learn. Especially after reading the article “Beyond cAMP: The regulation of Akt and GSK3 by Dopamine Receptors”. The article was so thick it was like swimming in a pool of jell-o. But luckily, with some handy tips that my science classes have taught me throughout my years at Concordia, I’ve learned that the only way to eat an elephant is one bite at a time.
 
Recently, my neurochemistry class read an article about the importance of dopamine and its receptors within a signaling pathway called the Akt/GSK3 pathway. This pathway is involved in all sorts of things such as glucose metabolism, apoptosis, and cell proliferation, transcription and migration.
 
There are many different kinds of receptors, and the ones most important within the Akt/GSK pathway are the D2 receptors. D2 receptors are a sub family of the dopamine receptors that activate other molecules that eventually inhibit the production of cAMP, an important second messenger molecule involved in many biological processes, and inhibit Akt phosphorylation of GSK3.
 
Once the D2 receptors are activated, they also inhibit the activation of Akt kinase, which allows the GSK3 kinase to proceed. This is done by the D2 receptors activating a complex, or group of molecules, to form together. This inhibits Akt activation, which means Akt cannot phosphorylate and causes GSK3 to activate.
 
In certain mood disorders, such as schizophrenia and bipolar disorder, there is an imbalance of dopamine within the brain. Many antipsychotic drugs are used to help this imbalance by working through the Akt/GSK3 pathway. These drugs act as antagonists on the D2 receptors, which causes an increase in Akt activation by not allowing the formation of the inhibitory complex, which in turn decreases GSK3 activity. Thus, too much activation of GSK3 can lead to negative side effects and have been seen to be a possible cause for these disorders.
 
It’s a lot to understand, especially after tearing the article apart only to simplify it to knowing simple mechanisms when there is so much more going on. But one thing is for sure, the brain is complex and there is always more to learn about it!