Reversal of hippocampal neuronal maturation by serotonergic antidepressants.

摘要: Serotonergic antidepressant drugs have been commonly used to treat mood and anxiety disorders, increasing evidence suggests potential use of these beyond current therapeutics. Facilitation adult neurogenesis in the hippocampal dentate gyrus has suggested be a candidate mechanism action drugs, but this may only one broad effects antidepressants. Here we show distinct unique serotonergic fluoxetine transforming phenotype mature granule cells. Chronic treatments mice with strongly reduced expression cell marker calbindin. The treatment induced active somatic membrane properties resembling immature cells markedly synaptic facilitation that characterizes dentate-to-CA3 signal transmission. These changes cannot explained simply by an increase newly generated neurons, best characterized as “dematuration” This dematuration developed along increases efficacy serotonin 5-HT4 receptor-dependent neuromodulation was attenuated lacking receptor. Our results suggest antidepressants can reverse established state neuronal maturation hippocampus, up-regulation receptor-mediated signaling play critical role Such reversal could affect proper functioning circuit, also cause some beneficial reinstating functions are lost during development.