Department of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
Neuroscience. 2011 Apr 14;179:256-66. doi: 10.1016/j.neuroscience.2011.01.046. Epub 2011 Jan 26.
A second wave of neuronal generation occurs in the ventrobasal nucleus of the rat thalamus (VB) during the first three postnatal weeks. The present study tested the hypotheses (1) that postnatal neurogenesis in the VB is neurotrophin-regulated and (2) that ethanol-induced changes in this proliferation are mediated by neurotrophins. The first studies examined the effects of neurotrophins on the numbers of cycling cells in ex vivo preparations of the VB from 3-day-old rats. The proportion of cycling (Ki-67-positive) VB cells was higher in cultured thalamic slices treated with neurotrophins than in controls. Interestingly, this increase occurred with nerve growth factor (NGF) alone or with a combination of NGF and brain-derived neurotrophic factor (BDNF), but not with BDNF alone. Based on these data, the VBs from young offspring of pregnant rats fed an ethanol-containing or an isocaloric non-alcoholic liquid diet were examined between postnatal day (P) 1 and P31. Studies used enzyme-linked immunosorbent assays and immunoblots to explore the effects of ethanol on the expression of neurotrophins, their receptors, and representative signaling proteins. Ethanol altered the expression of neurotrophins and receptors throughout the first postnatal month. Expression of NGF increased, but there was no change in the expression of BDNF. The high affinity receptors (TrkA and TrkB) were unchanged but ethanol decreased expression of the low affinity receptor, p75. One downstream signaling protein, extracellular signal-regulated kinase (ERK), decreased but Akt expression was unchanged. Thus, postnatal cell proliferation in the VB of young rat pups is neurotrophin-responsive and is affected by ethanol.
在出生后的前 3 周，大鼠丘脑腹侧基底核（VB）中会发生第二波神经元生成。本研究检验了以下假设：（1）VB 中的产后神经发生受神经营养因子调节；（2）这种增殖的乙醇诱导变化是由神经营养因子介导的。首先，研究检查了神经营养因子对来自 3 天大的大鼠 VB 的体外培养切片中细胞周期数量的影响。与对照组相比，经神经营养因子处理的培养丘脑切片中的 VB 细胞周期（Ki-67 阳性）比例更高。有趣的是，这种增加仅发生在神经生长因子（NGF）单独或与 NGF 和脑源性神经营养因子（BDNF）的组合中，而不是单独的 BDNF。基于这些数据，检查了在怀孕的大鼠中给予含酒精或等热量非酒精液体饮食后，其年轻后代的 VB 在出生后第 1 天（P）至第 31 天（P）之间的情况。研究使用酶联免疫吸附测定和免疫印迹法来探索乙醇对神经营养因子、其受体和代表性信号蛋白表达的影响。乙醇改变了整个第一个新生儿期的神经营养因子和受体的表达。NGF 的表达增加，但 BDNF 的表达没有变化。高亲和力受体（TrkA 和 TrkB）不变，但乙醇降低了低亲和力受体 p75 的表达。一种下游信号蛋白细胞外信号调节激酶（ERK）减少，但 Akt 的表达没有变化。因此，年轻大鼠幼仔 VB 中的产后细胞增殖对神经营养因子有反应，并且受乙醇影响。
