title: Prenatal stress inhibits neuronal maturation through downregulation of mineralocorticoid receptors.
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, which we found 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.
authors.affiliation: Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tamura
authors.forename: Mari
authors.initials: M
authors.lastname: Sajo
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Norio
authors.initials: N
authors.lastname: Matsuki
authors.forename: Ryuta
authors.initials: R
authors.lastname: Koyama
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D000451:Mineralocorticoid Receptor Antagonists; D009433:Neural Inhibition / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism* / Q000523:psychology; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis* / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism* / Q000523:psychology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid