Monday, June 07, 2010

Prozac reverses maturation of some brain cells

Here is some intriguing work from Kobayashi et al. showing that fluoxetine (Prozac) indices a dematuration of hippocampus dentate gyrus cells that reinstates synaptic plasticity that is reduced with development, thereby potentially causing beneficial effects on the adult brain. (These cells are key in learning and memory processes). Their results suggest that the state of neuronal maturation, including aberrant maturation, might be controlled or corrected in adults, a unique approach to treating neuronal dysfunctions associated with neurodevelopmental disorders. Some clips from the abstract:
Serotonergic antidepressant drugs have been commonly used to treat mood and anxiety disorders, and increasing evidence suggests potential use of these drugs beyond current antidepressant therapeutics. Facilitation of adult neurogenesis in the hippocampal dentate gyrus has been suggested to be a candidate mechanism of action of antidepressant drugs, but this mechanism may be only one of the broad effects of antidepressants. Here we show a distinct unique action of the serotonergic antidepressant fluoxetine in transforming the phenotype of mature dentate granule cells. Chronic treatments of adult mice with fluoxetine strongly reduced expression of the mature granule cell marker calbindin. The fluoxetine treatment induced active somatic membrane properties resembling immature granule cells and markedly reduced synaptic facilitation that characterizes the mature dentate-to-CA3 signal transmission. These changes cannot be explained simply by an increase in newly generated immature neurons, but best characterized as “dematuration” of mature granule cells...Our results suggest that serotonergic antidepressants can reverse the established state of neuronal maturation in the adult hippocampus...Such reversal of neuronal maturation could affect proper functioning of the mature hippocampal circuit, but may also cause some beneficial effects by reinstating neuronal functions that are lost during development.

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