Prenatal stress inhibits neuronal maturation through down regulation of mineralocorticoid receptors

Makoto Tamura, Mari Sajo, Akiyoshi Kakita, Norio Matsuki, Ryuta Koyama

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Prenatal stress (PS) increases the risk of depressive disorders in adult offspring. The pathophysiology of depressive disorders has been linked to hippocampal dysfunction; however, whether and how PS attenuates the development and function of hippocampal networks remains unknown. Using a rat model of PS, in which pregnant mothers receive daily restraint stress during late gestation and their offspring exhibit depressive-like behavior later in life, we show that PS impairs the morphological and functional maturation of hippocampal granule cells in adult offspring via the downregulated expression of mineralocorticoid receptors. PS reduced the dendritic complexity and spine density of neonatal-generated granule cells, which persists into adulthood. These granule cells exhibited depressed synaptic responses to stimulation of the medial perforant path. We further revealed that the expression of mineralocorticoid receptors, whichwefound is necessary for proper dendritic maturation in this study, was significantly downregulated in granule cells after PS. These results suggest that PS-induced downregulation of mineralocorticoid receptors attenuates neuronal maturation, which results in dysfunction of neuronal network in adulthood.

Original languageEnglish
Pages (from-to)11505-11514
Number of pages10
JournalJournal of Neuroscience
Volume31
Issue number32
DOIs
StatePublished - 10 Aug 2011
Externally publishedYes

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