Schizophrenia Research Institute, Sydney, 2010, Australia; Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, 2031, Australia; School of Psychiatry, University of New South Wales, Sydney, 2052, Australia.
Hippocampus. 2014 Feb;24(2):225-38. doi: 10.1002/hipo.22217. Epub 2013 Nov 13.
New neurons are continuously produced in the subgranular zone of the adult hippocampus and can modulate hippocampal plasticity across life. Adolescence is characterized by dramatic changes in sex hormone levels, and social and emotional behaviors. It is also an age for increased risk of psychiatric disorders, including schizophrenia, which may involve altered hippocampal neurogenesis. The extent to which testosterone and other testicular hormones modulate hippocampal neurogenesis and adolescent behavioral development is unclear. This study aimed to determine if removal of testicular hormones during adolescence alters neurogenesis in the male rhesus macaque hippocampus. We used stereology to examine levels of cell proliferation, cell survival and neuronal differentiation in late adolescent male rhesus macaques (4.6-yrs old) that had previously been gonadectomized or sham operated prior to puberty (2.4-yrs old). While the absence of adolescent testicular hormones had no effect on cell proliferation, cell survival was increased by 65% and indices of immature neuronal differentiation were increased by 56% in gonadectomized monkeys compared to intact monkeys. We show for the first time that presence of circulating testicular hormones, including testosterone, may decrease neuronal survival in the primate hippocampus during adolescence. Our findings are in contrast to existing studies in adults where testosterone tends to be a pro-survival factor and demonstrate that testicular hormones may reduce hippocampal neurogenesis during the age typical of schizophrenia onset.
新神经元在成年海马体的颗粒下区不断产生，并能调节整个生命过程中海马体的可塑性。青春期的特点是性激素水平、社会和情感行为的急剧变化。也是精神疾病风险增加的年龄，包括精神分裂症，这可能涉及海马体神经发生的改变。睾丸激素和其他睾丸激素调节海马体神经发生和青春期行为发育的程度尚不清楚。本研究旨在确定青春期去除睾丸激素是否会改变雄性恒河猴海马体的神经发生。我们使用体视学方法检查了先前在青春期前（2.4 岁）进行去势或假手术的青春期后期雄性恒河猴（4.6 岁）中海马体的细胞增殖、细胞存活和神经元分化水平。虽然青春期缺乏睾丸激素对细胞增殖没有影响，但与完整猴子相比，去势猴子的细胞存活增加了 65%，未成熟神经元分化指数增加了 56%。我们首次表明，循环睾丸激素的存在，包括睾酮，可能会减少青春期灵长类动物海马体中的神经元存活。我们的研究结果与成人中现有的研究结果相反，在成人中，睾酮往往是一种促进生存的因素，这表明睾丸激素可能会减少青春期时海马体的神经发生，而这正是精神分裂症发病的典型时期。
