Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/58185

TitleAntidepressant responsiveness in adulthood is permanently impaired after neonatal destruction of the neurogenic pool
Author(s)Yu, S.
Zutshi, I.
Stoffel, R.
Zhang, J.
Ventura-Silva, A. P.
Sousa, Nuno
Costa, P. S.
Holsboer, F.
Patchev, A.
Almeida, O. F. X.
KeywordsAnimals
Animals, Newborn
Antidepressive Agents
Apoptosis
Dexamethasone
Feedback, Physiological
Fluoxetine
Glucocorticoids
Hippocampus
Male
Neural Stem Cells
Neurogenesis
Neurons
Rats
Rats, Wistar
Issue date2017
PublisherNature Publishing Group (NPG)
JournalTranslational Psychiatry
Abstract(s)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.
TypeArticle
URIhttp://hdl.handle.net/1822/58185
DOI10.1038/tp.2016.255
ISSN2158-3188
Peer-Reviewedyes
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

Files in This Item:
File Description SizeFormat 
tp2016255.pdf986,68 kBAdobe PDFView/Open

Partilhe no FacebookPartilhe no TwitterPartilhe no DeliciousPartilhe no LinkedInPartilhe no DiggAdicionar ao Google BookmarksPartilhe no MySpacePartilhe no Orkut
Exporte no formato BibTex mendeley Exporte no formato Endnote Adicione ao seu ORCID