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应激、环境丰容和抗抑郁治疗对海马神经发生的区域依赖性和阶段特异性影响。

Region-dependent and stage-specific effects of stress, environmental enrichment, and antidepressant treatment on hippocampal neurogenesis.

机构信息

INSERM UMR930, Tours, France; Université François Rabelais, Tours, France.

出版信息

Hippocampus. 2013 Sep;23(9):797-811. doi: 10.1002/hipo.22134. Epub 2013 May 22.

Abstract

Chronic stress and depression are associated with decreased levels of hippocampal neurogenesis. On the other hand, antidepressants as well as environmental enrichment may rely in part on their pro-neurogenic effects to improve cognition and mood. Because a functional heterogeneity has been consistently reported along the septo-temporal axis of the hippocampus, regional changes in neurogenesis could differentially contribute to these effects and affect distinct hippocampal functions. Mapping these regional changes could therefore provide a better understanding of the function of newborn neurons. While some studies report region-specific effects of stress and antidepressants on neurogenesis, it is unclear whether these changes affect distinct populations of newborn neurons according to their developmental stage in a region-specific manner. By using endogenous markers and BrdU labeling we quantified the regional changes in cell proliferation and survival as well as in the number of neuronal progenitors and immature neurons following unpredictable chronic mild stress (UCMS), environmental enrichment (EE) and chronic fluoxetine (20 mg/kg/day) treatment along the septo-temporal axis of the hippocampus. EE promoted cell proliferation and survival of 4-week-old newborn cells as well as increased the number and proportion of post-mitotic immature neurons specifically within the septal hippocampus. By contrast, UCMS uniformly decreased cell proliferation, survival and immature newborn neurons but differentially affected progenitor cells with a decrease restricted to the temporal regions of the hippocampus. Whereas fluoxetine treatment in control mice affected proliferation and survival specifically in the temporal hippocampus, it reversed most of the UCMS-induced alterations all along the septo-temporal axis. These results highlight that different factors known for exerting a mood improving effect differentially regulate neurogenesis along the septo-temporal axis of the hippocampus. Such region and stage specific effects may correlate to distinct functional properties of newborn neurons along the septo-temporal axis of the hippocampus which may contribute differently to the pathophysiology of affective disorders.

摘要

慢性应激和抑郁与海马神经发生水平降低有关。另一方面,抗抑郁药以及环境丰富可能部分依赖于其促进神经发生的作用来改善认知和情绪。由于海马沿隔颞轴一直存在功能异质性,神经发生的区域变化可能会对这些作用产生不同的影响,并影响不同的海马功能。因此,对这些区域变化进行映射可以更好地了解新生神经元的功能。虽然一些研究报告了应激和抗抑郁药对神经发生的区域特异性影响,但尚不清楚这些变化是否会根据其在区域内的发育阶段以特定的方式影响不同的新生神经元群体。通过使用内源性标记物和 BrdU 标记,我们定量分析了不可预测的慢性轻度应激 (UCMS)、环境丰富 (EE) 和慢性氟西汀 (20mg/kg/天) 治疗沿海马隔颞轴引起的细胞增殖和存活以及神经前体细胞和未成熟神经元数量的区域变化。EE 促进了 4 周龄新生细胞的增殖和存活,并增加了处于有丝分裂后阶段的未成熟神经元的数量和比例,特别是在海马隔区。相比之下,UCMS 均匀地降低了细胞增殖、存活和未成熟的新生神经元,但对祖细胞有不同的影响,仅局限于海马的颞区。而氟西汀治疗在对照小鼠中仅影响颞叶海马的增殖和存活,它逆转了 UCMS 诱导的大部分改变,沿隔颞轴都有。这些结果强调了已知对情绪有改善作用的不同因素沿海马隔颞轴对神经发生的不同调节。这种区域和阶段特异性的影响可能与海马隔颞轴上新生神经元的不同功能特性相关,这些特性可能对情感障碍的病理生理学有不同的贡献。

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