Department of Biology, Middlebury College, Middlebury, VT 05753, USA.
Graduate School of Education, Stanford University, Stanford, CA 94305, USA.
Biomolecules. 2020 Feb 3;10(2):225. doi: 10.3390/biom10020225.
It is now well established that neurogenesis occurs throughout adulthood in select brain regions, but the functional significance of adult neurogenesis remains unclear. There is considerable evidence that steroid hormones modulate various stages of adult neurogenesis, and this review provides a focused summary of the effects of testosterone on adult neurogenesis. Initial evidence came from field studies with birds and wild rodent populations. Subsequent experiments with laboratory rodents have tested the effects of testosterone and its steroid metabolites upon adult neurogenesis, as well as the functional consequences of induced changes in neurogenesis. These experiments have provided clear evidence that testosterone increases adult neurogenesis within the dentate gyrus region of the hippocampus through an androgen-dependent pathway. Most evidence indicates that androgens selectively enhance the survival of newly generated neurons, while having little effect on cell proliferation. Whether this is a result of androgens acting directly on receptors of new neurons remains unclear, and indirect routes involving brain-derived neurotrophic factor (BDNF) and glucocorticoids may be involved. In vitro experiments suggest that testosterone has broad-ranging neuroprotective effects, which will be briefly reviewed. A better understanding of the effects of testosterone upon adult neurogenesis could shed light on neurological diseases that show sex differences.
现在已经证实,在特定的大脑区域,神经发生贯穿成年期,但成年神经发生的功能意义仍不清楚。有相当多的证据表明,类固醇激素调节成年神经发生的各个阶段,本综述重点总结了睾酮对成年神经发生的影响。最初的证据来自鸟类和野生啮齿动物种群的实地研究。随后,用实验室啮齿动物进行的实验测试了睾酮及其类固醇代谢物对成年神经发生的影响,以及诱导神经发生变化的功能后果。这些实验提供了明确的证据,表明睾酮通过雄激素依赖性途径增加海马齿状回区域的成年神经发生。大多数证据表明,雄激素选择性地增强新生成神经元的存活,而对细胞增殖几乎没有影响。雄激素是否直接作用于新神经元的受体尚不清楚,而涉及脑源性神经营养因子 (BDNF) 和糖皮质激素的间接途径可能参与其中。体外实验表明,睾酮具有广泛的神经保护作用,这将简要综述。更好地了解睾酮对成年神经发生的影响可以揭示具有性别差异的神经疾病。