title: Neonatal maternal separation up-regulates protein signalling for cell survival in rat hypothalamus.
abstract: We have previously reported that in response to early life stress, such as maternal hyperthyroidism and maternal separation (MS), the rat hypothalamic vasopressinergic system becomes up-regulated, showing enlarged nuclear volume and cell number, with stress hyperresponsivity and high anxiety during adulthood. The detailed signaling pathways involving cell death/survival, modified by adverse experiences in this developmental window remains unknown. Here, we report the effects of MS on cellular density and time-dependent fluctuations of the expression of pro- and anti-apoptotic factors during the development of the hypothalamus. Neonatal male rats were exposed to 3 h-daily MS from postnatal days 2 to 15 (PND 2-15). Cellular density was assessed in the hypothalamus at PND 21 using methylene blue staining, and neuronal nuclear specific protein and glial fibrillary acidic protein immunostaining at PND 36. Expression of factors related to apoptosis and cell survival in the hypothalamus was examined at PND 1, 3, 6, 9, 12, 15, 20 and 43 by Western blot. Rats subjected to MS exhibited greater cell-density and increased neuronal density in all hypothalamic regions assessed. The time course of protein expression in the postnatal brain showed: (1) decreased expression of active caspase 3; (2) increased Bcl-2/Bax ratio; (3) increased activation of ERK1/2, Akt and inactivation of Bad; PND 15 and PND 20 were the most prominent time-points. These data indicate that MS can induce hypothalamic structural reorganization by promoting survival, suppressing cell death pathways, increasing cellular density which may alter the contribution of these modified regions to homeostasis.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina and.
authors.forename: Claudine
authors.initials: C
authors.lastname: Irles
authors.forename: Alicia T
authors.initials: AT
authors.lastname: Nava-Kopp
authors.forename: Julio
authors.initials: J
authors.lastname: Morán
authors.forename: Limei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D034961:Antigens, Nuclear / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D053148:Caspase 3 / Q000096:biosynthesis; D002470:Cell Survival / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D007031:Hypothalamus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D008297:Male; D008426:Maternal Deprivation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D034961:Antigens, Nuclear; D051017:Apoptosis Regulatory Proteins; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C546339:Rbfox3 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3