Nawarawong Natalie N, Nickell Chelsea G, Hopkins Deann M, Pauly James R, Nixon Kimberly
College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY 40536, USA.
Brain Sci. 2021 Apr 15;11(4):499. doi: 10.3390/brainsci11040499.
Abstinence after alcohol dependence leads to structural and functional recovery in many regions of the brain, especially the hippocampus. Significant increases in neural stem cell (NSC) proliferation and subsequent "reactive neurogenesis" coincides with structural recovery in hippocampal dentate gyrus (DG). However, whether these reactively born neurons are integrated appropriately into neural circuits remains unknown. Therefore, adult male rats were exposed to a binge model of alcohol dependence. On day 7 of abstinence, the peak of reactive NSC proliferation, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. After six weeks, rats underwent Morris Water Maze (MWM) training then were sacrificed ninety minutes after the final training session. Using fluorescent immunohistochemistry for c-Fos (neuronal activation), BrdU, and Neuronal Nuclei (NeuN), we investigated whether neurons born during reactive neurogenesis were incorporated into a newly learned MWM neuronal ensemble. Prior alcohol exposure increased the number of BrdU+ cells and newborn neurons (BrdU+/NeuN+ cells) in the DG versus controls. However, prior ethanol exposure had no significant impact on MWM-induced c-Fos expression. Despite increased BrdU+ neurons, no difference in the number of activated newborn neurons (BrdU+/c-Fos+/NeuN+) was observed. These data suggest that neurons born during alcohol-induced reactive neurogenesis are functionally integrated into hippocampal circuitry.
酒精依赖后戒酒可使大脑许多区域，尤其是海马体，在结构和功能上得到恢复。神经干细胞（NSC）增殖显著增加以及随后的“反应性神经发生”与海马齿状回（DG）的结构恢复同时出现。然而，这些反应性产生的神经元是否能适当地整合到神经回路中仍不清楚。因此，对成年雄性大鼠采用酒精依赖的暴饮模型。在戒酒第7天，即反应性NSC增殖的高峰期，给大鼠注射溴脱氧尿苷（BrdU）以标记分裂细胞。六周后，对大鼠进行莫里斯水迷宫（MWM）训练，然后在最后一次训练 session 后90分钟处死。使用针对c-Fos（神经元激活）、BrdU和神经元核（NeuN）的荧光免疫组织化学，我们研究了反应性神经发生过程中产生的神经元是否被纳入新学习的MWM神经元集合。与对照组相比，先前的酒精暴露增加了DG中BrdU+细胞和新生神经元（BrdU+/NeuN+细胞）的数量。然而，先前的乙醇暴露对MWM诱导的c-Fos表达没有显著影响。尽管BrdU+神经元数量增加，但未观察到激活的新生神经元（BrdU+/c-Fos+/NeuN+）数量有差异。这些数据表明，酒精诱导的反应性神经发生过程中产生的神经元在功能上整合到了海马回路中。
