title: Prenatal stress induces long-term effects in cell turnover in the hippocampus-hypothalamus-pituitary axis in adult male rats.
abstract: Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations.
authors.affiliation: Department of Pediatrics, Universidad Autónoma de Madrid-Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Baquedano
authors.forename: Cristina
authors.initials: C
authors.lastname: García-Cáceres
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Diz-Chaves
authors.forename: Natalia
authors.initials: N
authors.lastname: Lagunas
authors.forename: Isabel
authors.initials: I
authors.lastname: Calmarza-Font
authors.forename: Iñigo
authors.initials: I
authors.lastname: Azcoitia
authors.forename: Luis M
authors.initials: LM
authors.lastname: Garcia-Segura
authors.forename: Jesús
authors.initials: J
authors.lastname: Argente
authors.forename: Julie A
authors.initials: JA
authors.lastname: Chowen
authors.forename: Laura M
authors.initials: LM
authors.lastname: Frago
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013312:Stress, Physiological / Q000502:physiology*; D013995:Time; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D007334:Insulin-Like Growth Factor I; C033668:calpastatin; D002154:Calpain; D053181:Caspase 8
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