Adrenal steroid influences on the survival of hippocampal neurons.
Adrenal steroid influences on the survival of hippocampal neurons.
复制标题
肾上腺类固醇影响海马神经元的存活。
DOI：
10.1016/0006-2952(90)90079-z
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发表时间：
1990
影响因子：
5.8
通讯作者：
Gould,E
中科院分区：
文献类型：
--
作者：
McEwen,BS;Gould,E
虽然神经细胞的选择性和程序性破坏在神经系统发育中起着重要作用[1]，但保护神经细胞免受破坏是成熟神经系统的一个重要方面。介导细胞存活和死亡的因素对于我们理解神经元的发育、维持和衰老具有特别的意义。许多化学因素已被证明影响细胞死亡的发展和响应损伤。例如，神经生长因子[Z]能够延迟或防止基底前脑神经元在手术损伤到其靶部位后的损失。在消极的一面，循环糖皮质激素加剧与短暂性缺血[3]和衰老[4，5]相关的神经损伤，也可能是严重社会压力的结果[6]。然而，糖皮质激素在神经元存活中的作用并不一致。最近的一份报告表明，大鼠肾上腺切除术（ADX）在3-4个月内导致海马结构齿状回神经细胞大量丢失[7]。这种损失可以通过在饮用水中维持ADX大鼠低水平的皮质酮来预防[7]。这些发现中的一个难题是，三分之一的ADX大鼠没有显示出齿状回内大量神经元丢失的任何明显证据[7]。这些差异效应特别令人惊讶，因为阿蒙角的锥体细胞和齿状回的颗粒细胞表达I型和II型肾上腺类固醇受体[8，9]。肾上腺皮质类固醇保护齿状回和糖皮质激素增强阿蒙角细胞丢失的明显矛盾要求我们更多地了解神经细胞死亡或存活的潜在机制。事实上，有多种机制和代理人参与神经元的破坏或生存，本文回顾了一些主要的机制，并讨论他们在肾上腺皮质类固醇对细胞存活的对比效应。
Whereas the selective and programmed destruction of nerve cells plays an important role in nervous system development [l], the preservation of nerve cells from destruction is an important aspect of the mature nervous system. The factors which mediate cell survival and death are of particular interest for our understanding of neuron al development, maintenance and aging. A variety of chemical factors have been shown to influence cell death developmentally and in response to injury. For example, nerve growth factor [Z] is able to retard or prevent loss of basal forebrain neurons following surgical lesions to their target sites. On the negative side, circulating glucocorticoids exacerbate neural damage associated with transient ischemia [3] and with aging] 4, 5], and possibly also as a result of severe social stress [6]. However, the role of glucocorticoids in neuronal survival is not uniformly negative. A recent report indicated that adrenalectomy (ADX) of rats results, within 3-4 months, in massive loss of nerve cells in the dentate gyrus of the hippocampal formation [7]. This loss can be prevented by maintaining the ADX rats on low levels of corticosterone in the drinking water [7]. One of the puzzles from these findings is that one-third of the ADX rats did not show any gross evidence of massive neuronal loss within the dentate gyrus [7]. These differential effects are particularly surprising because pyramidal cells of Ammon’s horn and granule cells of the dentate gyrus express both Type I and Type II adrenal steroid receptors [8, 9]. The apparent paradox of adrenal steroid protection of the dentate gyrus and glucocorticoid potentiation of cell loss in the Ammon’s horn demands that we understand more about underlying mechanisms by which nerve cells die or survive. In fact, there are multiple mechanisms and agents involved in neuronal destruction or survival, and this article reviews some of the principal mechanisms and discusses them in relation to the contrasting effects of adrenal steroids on cell survival.