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锂诱导的成年海马神经发生的影响沿应激小鼠的背腹轴呈地形分离。

Lithium-induced effects on adult hippocampal neurogenesis are topographically segregated along the dorso-ventral axis of stressed mice.

机构信息

School of Pharmacy, Department of Pharmacology and Therapeutics, University College Cork, Ireland.

出版信息

Neuropharmacology. 2012 Jan;62(1):247-55. doi: 10.1016/j.neuropharm.2011.07.015. Epub 2011 Jul 22.

Abstract

Adult hippocampal neurogenesis is an important process in the regulation of cognition, stress responsivity, and sensitivity to antidepressant and mood stabiliser drugs. Increasing evidence suggests that the hippocampus is functionally divided along its axis with the ventral hippocampus (vHi) playing a preferential role in stress- and anxiety-related processes, while the dorsal hippocampus (dHi) is crucial for spatial learning and memory. However, it is currently unclear whether stress or the medications used to treat stress-related disorders, preferentially affect neurogenesis in the vHi rather than dHi. The aim of this study was to determine whether the mood stabiliser, lithium, preferentially affects cell proliferation and survival in the vHi rather than dHi under stress conditions. To this end, mice of the stress-sensitive strain, BALB/c, underwent chronic exposure to immobilisation stress plus lithium treatment (0.2% lithium-supplemented diet), and the rates of cell proliferation and survival were compared in the dHi and vHi. Lithium preferentially increased cell proliferation in the vHi under stress conditions only. This increase in cell proliferation was secondary to reductions in the survival of newly-born cells. Moreover, lithium-induced decreases in cell survival in the vHi were only observed under stress conditions. Taken together, the data suggest that the turnover of newly-born cells in response to chronic stress and lithium treatment occurs predominantly in the vHi rather than the dHi. This article is part of a Special Issue entitled 'Anxiety and Depression'.

摘要

成人海马神经发生是调节认知、应激反应以及对抗抑郁药和情绪稳定剂药物敏感性的重要过程。越来越多的证据表明,海马沿着其轴被功能性地划分,腹侧海马(vHi)在应激和焦虑相关过程中发挥优先作用,而背侧海马(dHi)对空间学习和记忆至关重要。然而,目前尚不清楚是应激还是用于治疗应激相关障碍的药物优先影响 vHi 中的神经发生,而不是 dHi。本研究的目的是确定情绪稳定剂锂在应激条件下是否优先影响 vHi 中的细胞增殖和存活,而不是 dHi。为此,应激敏感品系 BALB/c 小鼠接受慢性束缚应激加锂处理(0.2%锂补充饮食),并比较 dHi 和 vHi 中的细胞增殖和存活速度。只有在应激条件下,锂才优先增加 vHi 中的细胞增殖。这种细胞增殖的增加是由于新生成细胞的存活减少所致。此外,仅在应激条件下才观察到锂诱导的 vHi 中细胞存活减少。总之,数据表明,新生成细胞对慢性应激和锂处理的反应性更替主要发生在 vHi 中,而不是 dHi 中。本文是题为“焦虑和抑郁”的特刊的一部分。

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