New neurons and a new therapeutic target

The recent discovery that the human brain produces new neurons throughout life has led us to re-evaluate how we think about our brains and their plasticity, as well as examine potential new targets for psychiatric treatment.

In the narrow space between your ears, a roughly three-pound lump of tissue (composed mostly of water) contains everything that makes you who you are. Your brain is responsible for all of your memories, emotions, actions and aspirations. The human brain is also the source of all of our joy and misery, and understanding its workings offers hope for the amelioration of psychiatric suffering and, possibly, greater potential for happiness and enjoyment of life. However, one difficulty in dealing with the complexity of psychiatric disorders is that frequently multiple theories arise to help explain the origin or cause of any particular condition. 

Depression is one example of this; there are many hypotheses attempting to explain this debilitating condition that affects more than 120 million people worldwide. One of the most widely-known theories is the 'monoaminergic theory' of depression, which focuses on neurotransmitters (chemicals used by neurons for communication) like serotonin. However, in this article I will try to give a brief review of a more recent theory, the 'neurogenic theory' of depression.

Up until relatively recently, it was believed that the brain stopped producing new neurons after development; as the famous neuroscientist Santiago Ramon y Cajal said around a century ago, "In the adult centers, the nerve paths are something fixed, and immutable: everything may die, nothing may be regenerated". However, the creation of new neurons in the mature brain, a process known as 'adult neurogenesis', was confirmed relatively recently in humans.

But there are some mysterious aspects to this phenomenon. For one thing, there initially seems to be only two clearly neurogenic areas in the brain; the olfactory bulb, and the dentate gyrus of the hippocampus. There's some early evidence to suggest other parts of the brain may be neurogenic as well, but even in these areas, the number of new cells produced seems to be limited at best. So this raises some questions; why just these few areas in particular, and not others? And what is the function of these new cells?

Although adult neurogenesis is still a relatively new discovery, it's become something of a hot topic in neuroscience, so we have some preliminary answers to the questions I just posed. For one thing, these new neurons seem to have special properties, in that immature neurons seem more 'plastic' or flexible in their firing responses than other cells. We also have some hints at their function, particularly with hippocampal neurogenesis; it's been shown to be involved in learning and memory and, most importantly for this entry, has been associated with emotional functioning.

This brings us back to the neurogenic theory of depression, an idea that essentially states that if the rate of production of these new 'special' neurons decreases, depressive symptoms may appear or be increased in severity, whereas increases in the rate of adult hippocampal neurogenesis can reduce the severity or appearance of depressive symptoms. Although this idea is only a few years old, there's some evidence supporting it. For one thing, factors that seem to make depression worse, such as stress, also decrease hippocampal neurogenesis, and factors that have been shown to improve depressive symptoms, such as antidepressant drugs and electroconvulsive treatment, also increase hippocampal neurogenesis. Human depressed patients also show decreased volume of the hippocampus. In addition, the delay between starting antidepressant medication and the amelioration of depressive symptoms, roughly four to six weeks, closely mirrors the time necessary for newly-proliferated cells spurred by this medicine to develop into functional neurons. And finally, experiments using animal models have shown that factors that increase neurogenesis also induce antidepressant behaviour.

So the neurogenic theory of depression, although it's still a relatively new idea, has the potential to offer exciting insight into depression and other psychiatric conditions, including treatment applications; if increasing the rate of neurogenesis can improve depression and depressive symptoms, then we can potentially develop new medications and treatments aimed specifically at increasing adult neurogenesis.

It's important to keep in mind that a lot of the theories scientists have developed concerning psychiatric illness are still preliminary, and a lot of important research is still needed before we can provide the definitive answers patients and their families are desperate to hear. However, the silver lining is that we're constantly getting closer to finding those answers, and offering hope to those searching for it.

- Ian Mahar

[Adapted from an article initially published here]

"Parkinson's Disease: Working Towards a Cure": Part 1-- The Basics

This is the first post from a three part series written by Andrew Greene, a graduate student at McGill University studying Parkinson's Disease. 

James Parkinson was a British apothecary-surgeon best known for his medical report entitled "An Essay on the Shaking Palsy." Published in 1817, it was a detailed description of the disorder that would one day be known as Parkinson's disease. The disease can bring on a variety of symptoms, many of which we're only just beginning to appreciate, but the best understood are the movement related effects. Typical symptoms include tremors of the limbs and difficulties performing movements, especially ones that have multiple parts, such as reaching out to a cup, grabbing it, and bringing it to your lips. There is presently no cure for Parkinson's disease, but there are a number of treatments available to at least temporarily alleviate the symptoms, and these will be discussed in detail in part 2.
Despite the fact that Parkinson's disease is primarily a movement disorder, the muscles themselves generally remain healthy. It's actually a part of the brain involved in coordinating movement that has traditionally been said to be most prominently affected by the disease. This part of the brain is called the substantia nigra, which means black substance, referring to its characteristic dark colour compared to surrounding brain regions. The substantia nigra is located near the center of the brain and contains neurons that secrete a chemical called dopamine. Dopamine is a type of neurotransmitter, which are a class of chemicals that neurons emit in order to communicate with each other.
Dopamine is best known for its role in the brain's reward system, in which it's used to provide feelings of pleasure and enjoyment in response to things such as food, sex, and certain drugs. However, dopamine released by the substantia nigra also plays a critical role in modulating the activity of the striatum, a brain region that is essential in planning and coordinating movements. The striatum is the origin of two neural pathways that exert opposite effects on movement. The first of these is the so called direct pathway, which is thought to facilitate and reinforce intended movements. The second is the indirect pathway, which is thought to be responsible for inhibiting unwanted or inappropriate motion. Dopamine released by the substantia nigra helps maintain a balance between these two pathways by increasing the activity of the former and decreasing the activity of the latter.
In Parkinson's disease the dopamine-emitting neurons of the substantia nigra die off, which tips the delicate balance between the direct and indirect pathways. The result is too much activity in the indirect, motion-inhibiting pathway and too little in the direct, motion-facilitating pathway, which ultimately makes it exceedingly difficult for a patient to move. Why dopamine-emitting neurons of the substantia nigra die in Parkinson's disease is not known, though research over the last few decades has gone a long way towards solving the mystery, as we'll see in Part 3. Uncovering the reasons for their death is the first step in learning how to stop these neurons from dying, leading to better treatments and hopefully even a cure.

Stay tuned for Part 2: Current Treatments and Part 3: Towards a Cure. Coming soon! 

Welcome to the BAWMontreal Brain Blog!

Hi!

Thanks for clicking on the Blog link on the BAW Montreal website! This blog will deal with current and interesting research in the field of neuroscience, written in an easily readable and understandable way. Several university students from across Montreal will be blogging about their research and other topics throughout the year. Stay tuned for the first post! Coming soon!