Shome Ashna, Sultana Razia, Siddiqui Alina, Romeo Russell D
Department of Psychology and Neuroscience and Behavior Program, Barnard College of Columbia University, New York City, NY, United States.
Front Behav Neurosci. 2018 Aug 24;12:192. doi: 10.3389/fnbeh.2018.00192. eCollection 2018.
Adolescent development is marked by significant changes in neurobiological structure and function. One such change is the substantial adolescent-related decline in cellular proliferation and neurogenesis in the dentate gyrus of the hippocampal formation. Though the behavioral implications of these developmental shifts in cell proliferation are unclear, these changes might contribute to the altered cognitive and emotional functions associated with puberty and adolescence. The significant decrease in cellular proliferation throughout adolescence might make the hippocampus more vulnerable to perturbations during this developmental stage, particularly to factors known to disrupt neurogenesis, such as chronic exposure to stress-related hormones. To examine this possibility, we first measured cellular proliferation in the dentate gyrus of male and female C57BL/6N mice before and after adolescence and then assessed both cellular proliferation and the number of immature neurons in mice treated with oral corticosterone for 4 weeks during either adolescence or adulthood. We found significant age-related decreases in hippocampal cellular proliferation in both males and females. Though the greatest decrease in proliferation was during adolescence, we also observed that proliferation continued to decline through young adulthood. Despite the significant effect of chronic oral corticosterone on body weight gain in both the adolescent- and adult-treated males and females and the subtle, but significant suppressive effect of corticosterone on the number of immature neurons in the adolescent-treated males, cell proliferation in the hippocampus was unaffected by these treatments. These data show that the substantial adolescent-related change in cellular proliferation in the dentate gyrus is largely unaffected by chronic oral corticosterone exposure in males and females. Thus, despite being vulnerable to the metabolic effects of these chronic corticosterone treatments, these results indicate that the developmental changes in cellular proliferation in the dentate gyrus are relatively resilient to these treatments in mice.
青少年发育的特点是神经生物学结构和功能发生显著变化。其中一个变化是海马结构齿状回中与青少年相关的细胞增殖和神经发生大幅下降。尽管这些细胞增殖发育变化的行为影响尚不清楚，但这些变化可能导致与青春期和青少年期相关的认知和情感功能改变。整个青少年期细胞增殖的显著下降可能使海马在这个发育阶段更容易受到干扰，特别是受到已知会破坏神经发生的因素的影响，如长期暴露于与压力相关的激素。为了检验这种可能性，我们首先测量了雄性和雌性C57BL/6N小鼠在青春期前后齿状回中的细胞增殖，然后评估了在青春期或成年期接受4周口服皮质酮治疗的小鼠的细胞增殖和未成熟神经元数量。我们发现，雄性和雌性小鼠的海马细胞增殖均随年龄显著下降。虽然增殖下降最大的时期是青春期，但我们也观察到，在青年期增殖仍持续下降。尽管长期口服皮质酮对青春期和成年期接受治疗的雄性和雌性小鼠的体重增加有显著影响，且皮质酮对青春期接受治疗的雄性小鼠未成熟神经元数量有细微但显著的抑制作用，但海马中的细胞增殖不受这些治疗的影响。这些数据表明，齿状回中与青少年相关的细胞增殖的显著变化在很大程度上不受雄性和雌性长期口服皮质酮暴露的影响。因此，尽管易受这些慢性皮质酮治疗的代谢影响，但这些结果表明，齿状回中细胞增殖的发育变化在小鼠中对这些治疗具有相对的抵抗力。
