کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5816054 | 1556654 | 2011 | 13 صفحه PDF | دانلود رایگان |

Synaptic input activity affects the neurogenesis in adult hippocampal dentate gyrus (DG), while the input activity is potentiated by neurosteroid pregnenolone sulfate (PREGS). This study focused on exploring the effects of PREGS on the survival of newborn neurons in the DG of adult male mice. Proliferating cells were labeled with bromodeoxyuridine (BrdU) and injection (i.c.v.) of PREGS (3 nmol for two successive days) was made on various paired days from 0-1 to 20-21 after BrdU-injection. PREGS given on day 11-12 or 15-16, roughly corresponding to the prophase of synaptogenesis, produced an approximately 2-fold increase in the number of 22-day-old BrdU+ cells. Hippocampal slices, which were prepared 60 min after the in vivo PREGS-injection and followed by 60 min perfusion with artificial cerebrospinal fluid (ACSF), showed a sustained ( > 60 min) increase in the presynaptic glutamate release at perforant path-granule cell synapses. PREGS-inducted presynaptic potentiation required a co-activation of α7 nicotinic acetylcholine receptor (α7nAChR), NMDA receptor (NMDAr) and sigma-1 receptor (Ï1R), while its maintenance after PREGS-washout depended only on NMDAr and neuronal NO synthase (nNOS) activation. PREGS enhanced the NMDAr-mediated nNOS expression to increase presynaptic glutamate release via a retrograde NO signaling. The sustained presynaptic potentiation was critical to keep the PREGS-enhanced survival of newborn neurons in an NMDAr-dependent manner. These results for the first time provide in vivo evidence that PREGS enhances the survival of newborn neurons in adult animals through the potentiation of synaptic input activity.
Research highlights⺠PREGS enhances NMDAr-dependent survival of newborn neurons in DG of adult mice. ⺠PREGS-enhanced neurogenesis depends on a sustained presynaptic potentiation. ⺠PREGS-induced presynaptic potentiation requires activation of α7nAChR, NMDAr and Ï1R. ⺠After washing PREGS the sustained presynaptic potentiation is dependent on NMDAr.
Journal: Neuropharmacology - Volume 60, Issues 2â3, FebruaryâMarch 2011, Pages 529-541