Monday, April 19, 2010

Links Between Adult Neurogenesis and Behavioral Disorders

Functional Neurogenesis has a great article on some recent research into neurogenesis (creation of new neurons in the brain) in adults. It seems that decreased (or absent) neurogenesis makes us more susceptible to various issues, such as addiction or stroke.

Increased neurogenesis is not (necessarily) the opposite of reduced neurogenesis

Jason Snyder | 04/15/2010

Two recent papers have attracted a lot of media attention because they draw direct links between adult neurogenesis and behavioral disorders: Noonan et al. showed that rats lacking adult neurogenesis (stopped with irradiation) are more susceptible to cocaine addiction. Jin et al. showed that mice lacking adult neurogenesis (using a transgenic model) suffer greater infarct size and have more severe motor deficits after stroke.

While the papers themselves have important implications, what caught my attention was the angle taken by press releases: both articles studied the effects of reducing neurogenesis but the media focused on potential benefits of increasing neurogenesis. See speculation that antidepressants, by increasing neurogenesis, might be stroke-protective here. And, from Science Daily:

While the research specifically focused on what happens when neurogenesis is blocked, the scientists said the results suggest that increasing adult neurogenesis might be a potential way to combat drug addiction and relapse.

It may very well be the case that increasing neurogenesis is good in the same way decreasing neurogenesis is bad but it shouldn’t be assumed – maybe we have all the neurogenesis we need and, while completely arresting neurogenesis could be harmful, increasing neurogenesis beyond normal levels is just redundant.

Read the rest of the post.
Here is another take on neurogenesis, as it relates to depression, from an article in 2003 (Molecular Interventions). The article presents info on the increase in neurogenesis as a result of antidepressant use. However, they raise issues about the connection of drug use, hippocampal neurogenesis, and decreased depression.
The rate of adult neurogenesis fluctuates in response to several environmental factors. Chronic stress, which can lead to neuronal apoptosis and dendritic atrophy, certainly affects the overall rate of neurogenesis in the adult brain. Depression, which arises from several causes, including chronically stressful situations, is known to correlate with altered hippocampal morphology. But is the link between depression and neuronal regeneration merely coincidental? Recent studies indicate that ingestion of antidepressants leads to increased neurogenesis in the hippocampus. However, the hippocampus is generally thought important for learning and memory—not for “mood” state—thus, there is much more to the story that requires clarification. Also, caveats abound in the interpretation of neurogenesis in the amelioration of depression; nonetheless, these results are quite intriguing and might point to better design and prediction of new-generation antidepressants.
And here is another take (Psychiatry MCC) that suggests there is an emotional component the ventral portion of the hippocampus that is influenced by neurogenesis.

Does hippocampal neurogenesis matter?

Dr. Barlow: We believe it does. Of course, we are just beginning to understand the relevance of neurogenesis in the clinical realm. Actually, the hippocampus is in a unique position to influence and be influenced by multiple brain areas that are associated with mood and cognition. Some recent studies have suggested that neurogenesis in the ventral portion of the hippocampus is associated with emotional behavior.[3] Remarkably, it has been demonstrated that every commercially available antidepressant is neurogenic, and that some putative antidepressants that have failed to be approved were not neurogenic.[4,5] Furthermore, using mouse models, Rene Hen at Columbia University has shown that knocking out neurogenesis actually blocks antidepressant action.[5]

How can this knowledge about neurogenesis help with new drug discovery?

Dr. Barlow: Based upon our hypothesis that hippocampal neurogenesis is a necessary factor for successful antidepressant activity, we believe we can find new drugs that are at least as potent as the currently marketed antidepressants that possess entirely different mechanisms of action. At BrainCells, we have developed a multifaceted in-vitro and in-vivo drug discovery platform that can identify drug candidates that are both highly neurogenic and likely to be safe in man as well. The in-vitro studies utilize proprietary human stem cell assays that allow us to explore several individual components of neurogenesis. Once a neural precursor cell is born, it undergoes specific developmental stages, including proliferation, migration into the granule cell layer, differentiation, and integration into the existing hippocampal neuronal network as fully functional, mature neurons. As the figure to the left demonstrates, we can evaluate neuronal proliferation, differentiation, migration, and survival. Each of these aspects of neurogenesis may have clinical relevance.

I think there is still a lot of research that needs to be done to fully understand how neurogenesis works, and why it happens.

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