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Antidepressant responsiveness in adulthood is permanently impaired after neonatal destruction of the neurogenic pool

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Item Type:Article
Title:Antidepressant responsiveness in adulthood is permanently impaired after neonatal destruction of the neurogenic pool
Creators Name:Yu, S. and Zutshi, I. and Stoffel, R. and Zhang, J. and Ventura-Silva, A.P. and Sousa, N. and Costa, P.S. and Holsboer, F. and Patchev, A. and Almeida, O.F.X.
Abstract:The dynamic turnover of hippocampal neurons is implicated in the regulation of cognitive and affective behavior. Extending our previous demonstration that administration of dexamethasone (ND) to neonatal rats depletes the resident population of neural precursor cells (NPC) and restrains the size of the neurogenic regions, we now show that the adverse effects of ND persist into adulthood. Specifically, ND impairs repletion of the neurogenic pool and neurogenesis; ND also compromises cognitive performance, the ability to actively adapt to an acute stressor and, the efficacy of glucocorticoid (GC) negative feedback. Interestingly, although ND depletes the neurogenic pool, it does not permanently abolish the proliferative machinery of the residual NPC population; however, ND increases the susceptibility of hippocampal granule neurons to apoptosis. Although the antidepressant fluoxetine (FLX) reverses the latter phenomenon, it does not replenish the NPC pool. Treatment of ND-treated adult rats with FLX also improves GC negative feedback, albeit without rescuing the deleterious effects of ND on behavior. In summary, ND leads to protracted disruption of mental functions, some of which are resistant to antidepressant interventions. We conclude that manipulation of the NPC pool during early life may jeopardize the therapeutic potential of antidepressants in adulthood.
Keywords:Animals, Newborn, Antidepressive Agents, Apoptosis, Dexamethasone, Fluoxetine, Glucocorticoids, Hippocampus, Neural Stem Cells, Neurogenesis, Neurons, Physiological Feedback, Animals, Rats
Source:Translational Psychiatry
Publisher:Nature Publishing Group
Page Range:e990
Date:3 January 2017
Official Publication:https://doi.org/10.1038/tp.2016.255
PubMed:View item in PubMed

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