Antidepressant responsiveness in adulthood is permanently impaired after neonatal destruction of the neurogenic pool
| Autor: | Alexandre V. Patchev, Osborne F. X. Almeida, Patrício Costa, Ipshita Zutshi, Shuang Yu, Florian Holsboer, Jingzhong Zhang, Rainer Stoffel, Nuno Sousa, Ana Paula Ventura-Silva |
|---|---|
| Přispěvatelé: | Universidade do Minho |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Neurogenesis Population Apoptosis Hippocampal formation Hippocampus Dexamethasone 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Neural Stem Cells Internal medicine Fluoxetine medicine Animals Rats Wistar education Glucocorticoids Biological Psychiatry Feedback Physiological Neurons education.field_of_study Science & Technology Dentate gyrus Neural stem cell Antidepressive Agents Rats Psychiatry and Mental health 030104 developmental biology Endocrinology Animals Newborn Antidepressant Original Article Psychopharmacology Function and Dysfunction of the Nervous System Psychology 030217 neurology & neurosurgery Glucocorticoid medicine.drug |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP Translational Psychiatry TRANSLATIONAL PSYCHIATRY |
| Popis: | 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. We thank Albin Varga and his team for invaluable help with animal housing and care. This study represents a contribution from the SwitchBox Consortium, supported by the European FP7 (Contract 259772), with additional suuport from the National Key Research & Development Program of China (2016YFC1306600) to YS. The funders did not have any role in the design or execution of the study and had no influence over the interpretation of its results or the writing of the paper. The research was conducted in the absence of commercial or financial relationships that could be construed as a potential conflict of interest. info:eu-repo/semantics/publishedVersion |
| Databáze: | OpenAIRE |
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