Hippocampal volume loss is a hallmark of clinical depression. Chronic stress produces volume loss in the hippocampus in humans and atrophy of CA3 pyramidal cells and suppression of adult neurogenesis in rodents. To investigate the relationship between decreased adult neurogenesis and stress-induced changes in hippocampal structure and volume, we compared the effects of chronic unpredictable restraint stress and inhibition of neurogenesis in a rat pharmacogenetic model. Chronic unpredictable restraint stress over 4 weeks decreased total hippocampal volume, reflecting loss of volume in all hippocampal subfields and in both dorsal and ventral hippocampus. In contrast, complete inhibition of adult neurogenesis for 4 weeks led to volume reduction only in the dentate gyrus. With prolonged inhibition of neurogenesis for 8 or 16 weeks, volume loss spread to the CA3 region, but not CA1. Combining stress and inhibition of adult neurogenesis did not have additive effects on the magnitude of volume loss but did produce a volume reduction throughout the hippocampus. One month of chronic unpredictable restraint stress and inhibition of adult neurogenesis led to atrophy of pyramidal cell apical dendrites in dorsal CA3 and to neuronal reorganization in ventral CA3. Stress also significantly affected granule cell dendrites. The findings suggest that adult neurogenesis is required to maintain hippocampal volume but is not responsible for stress-induced volume loss.

中文翻译：

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压力和成人神经发生的丧失会不同程度地减少海马体积


海马体积减少是临床抑郁症的标志。慢性压力会导致人类海马体积减少、CA3 锥体细胞萎缩以及啮齿类动物成体神经发生的抑制。为了研究成年神经发生减少与应激引起的海马结构和体积变化之间的关系，我们在大鼠药物遗传学模型中比较了慢性不可预测的约束应激和神经发生抑制的影响。超过 4 周的慢性不可预测的束缚压力减少了海马总体积，反映了所有海马亚区以及背侧和腹侧海马的体积损失。相比之下，完全抑制成体神经发生 4 周仅导致齿状回体积减少。随着神经发生的长期抑制 8 或 16 周，体积损失会扩散到 CA3 区域，但不会扩散到 CA1。将应激和成人神经发生的抑制相结合不会对体积损失的程度产生附加影响，但确实会导致整个海马体的体积减少。一个月的慢性不可预测的束缚应激和对成体神经发生的抑制导致背侧 CA3 锥体细胞顶端树突萎缩和腹侧 CA3 神经元重组。压力也显着影响颗粒细胞树突。研究结果表明，成人神经发生是维持海马体积所必需的，但与压力引起的体积损失无关。