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Introduction: Rapid effects of estrogens within the hippocampus of rodents are dependent upon cell-signaling cascades, and activation of these cascades by estrogens varies by sex. Whether these pathways are rapidly activated within the dentate gyrus (DG) and CA1 by estrogens across sex and the anatomical longitudinal axis has been overlooked. Methods: Gonadally intact female and male rats were given either vehicle or physiological systemic low (1.1 µg/kg) or high (37.3 µg/kg) doses of 17β-estradiol 30 min prior to tissue collection. To control for the effects of circulating estrogens, an additional group of female rats was ovariectomized (OVX) and administered 17β-estradiol. Brains were extracted, and tissue punches of the CA1 and DG were taken along the longitudinal hippocampal axis (dorsal and ventral) and analyzed for key mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) cascade phosphoproteins. Results: Intact females had higher Akt pathway phosphoproteins (pAkt, pGSK-3β, and pp70S6K) than males in the DG (dorsal and ventral) and lower pERK1/2 in the dorsal DG. Most effects of 17β-estradiol on cell signaling occurred in OVX animals. In OVX animals, 17β-estradiol increased cell signaling of MAPK and Akt phosphoproteins (pERK1/2, pJNK, pAkt, and pGSK-3β) in the CA1 and pERK1/2 and pJNK DG. Discussion/Conclusions: Systemic 17β-estradiol treatment rapidly alters phosphoprotein levels in the hippocampus, dependent on reproductive status, and intact females have greater expression of Akt phosphoproteins than that in intact males in the DG. These findings shed light on underlying mechanisms of sex differences in hippocampal function and response to interventions that affect MAPK or Akt signaling. [ABSTRACT FROM AUTHOR]

Gonadal and stress hormones modulate neuroplasticity and behaviour. This review focuses on our findings over the past decade on the effects of estrogens and androgens on hippocampal neurogenesis, hippocampus-dependent learning and memory and the effects of reproductive experience in the rodent. Evidence suggests that acute estradiol initially enhances and subsequently suppresses cell proliferation in the dentate gyrus of adult female rodents. Repeated exposure to estradiol modulates hippocampal neurogenesis and cell death in adult female, but not male, rodents while, testosterone and dihydrotestosterone upregulate hippocampal neurogenesis in adult male rodents. Estradiol dose-dependently affects different brain regions involved in working memory (prefrontal cortex, hippocampus), reference memory (hippocampus) and conditioned place preference (amygdala). Pregnancy and motherhood differentially regulate adult hippocampal neurogenesis and spatial working memory in the dam after weaning. These studies and others demonstrate that the female brain responds to steroid hormones differently than the male brain. It is of the upmost importance to investigate the effects on neuroplasticity and behaviour in both the male and the female, particularly when modelling diseases that exhibit sex differences in incidence, etiology or treatment. Keywords: estradiol, neurogenesis, learning and memory, hippocampus, reproductive experience Les hormones de stress et gonadiques modulent la neuroplasticite et le comportement. Cette revue met l'accent sur Ies decouvertes des dernieres decennies quant aux effets des estroge, nes et des androgbnes sur la neurogenese de l'hippocampe, l'apprentissage dependant de l'hippocampe et les effets de l'experience de reproduction chez les rongeurs. Les donnees suggbrent qu'une quantite importante d'oestradiol augmente initialement puis diminue subsequemment la proliferation cellulaire dans le gyrus dente des rongeurs femelles adultes. Une exposition repetee a l'oestradiol module la neurogenese de l'hippocampe et la mort cellulaire chez les rongeurs femelles, mais pas chez les males, alors que la testosterone et la dihydrotestosterone regulent positivement la neurogenese de l'hippocampe chez les rongeurs adultes males. L'oestradiol peut affecter, independamment de la dose, differentes regions du cerveau impliquees dans la memoire de travail (cortex prefrontal et hippocampe), la memoire de reference (hippocampe) et la preference spatiale conditionnee (amygdale). La grossesse et la maternite regulent differemment la neurogenese de l'hippocampe et la memoire de travail chez les rongeurs femelles adultes apres la periode de sevrage. Ces etudes et d'autres demontrent que le cerveau de la femelle reagit differemment aux hormones steroidiennes que le cerveau des males. Il est de la plus grande importance d'en etudier Ies effets sur la neuroplasticite et le comportement autant chez les males que les femelles, particulierement lors de la modelisation de pathologies dont l'incidence, l'etiologie ou le traitement differe selon le sexe. Mots-cles: oestradiol, neurogenese, apprentissage et memoire, hippocampe, experience de reproduction

Sleep deprivation (SD) can suppress cell proliferation in the hippocampal dentate gyrus of adult male rodents, suggesting that sleep may contribute to hippocampal functions by promoting neurogenesis. However, suppression of cell proliferation in rats by the platform-over-water SD method has been attributed to elevated corticosterone (Cort), a potent inhibitor of cell proliferation and nonspecific correlate of this procedure. We report here results that do not support this conclusion. Intact and adrenalectomized (ADX) male rats were subjected to a 96-h SD using multiple- and single-platform methods. New cells were identified by immunoreactivity for 5-bromo-2'-deoxyuridine (BrdU) or Ki67 and new neurons by immunoreactivity for BrdU and doublecortin. EEG recordings confirmed a 95% deprivation of rapid eye movement (REM) sleep and a 40% decrease of non-REM sleep. Cell proliferation in the dentate gyrus was suppressed by up to 50% in sleep-deprived rats relative to apparatus control or home cage control rats. This effect was also observed in ADX rats receiving continuous low-dose Cort replacement via subcutaneous minipumps but not in ADX rats receiving Cort replacement via drinking water. In these latter rats, Cort intake via water was reduced by 60% during SD; upregulation of cell proliferation by reduced Cort intake may obscure inhibitory effects of sleep loss on cell proliferation. SD had no effect on the percentage of new cells expressing a neuronal phenotype. These results demonstrate that the Cort replacement method is critical for detecting an effect of SD on cell proliferation and support a significant role for sleep in adult neurogenesis. cell proliferation; hippocampus; rapid eye movement sleep; stress; corticosterone