McEwen B S
Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10021.
Ann N Y Acad Sci. 1994 Nov 30;746:134-42; discussion 142-4, 178-9. doi: 10.1111/j.1749-6632.1994.tb39223.x.
The unexpected discovery in 1968 that the hippocampus takes up and retains adrenal steroids has leds to equally unanticipated findings regarding the actions of hormones on the brain and the ways in which the brain is capable of changing in response to the hormonal milieu. First were indications that adrenal steroids adversely affect pyramidal neurons of the hippocampus and cause damage during aging and as a result of severe and prolonged stress. Atrophy of dendrites, particularly in the CA3 region, appears to be an early index of these effects. Second was evidence that the dentate gyrus undergoes atrophy and granule neuron death after adrenalectomy; perhaps as a result of this neuronal death, neurogenesis is stimulated in dentate gyrus of adult rats. Third are recent indications that excitability of hippocampal neurons, including the ability to generate long-term potentiation (LTP), is regulated biphasically by adrenal steroids. One important goal of current research is to understand the role of type I and type II receptors for adrenal steroids in hormonally-induced hippocampal plasticity. Type I receptors appear to play a role in containing programmed-cell death and the rate of neurogenesis; they also regulate key neurochemical features of dentate gyrus and Ammon's horn; and they facilitate LTP. Present information indicates that type II receptors inhibit LTP and may play a role in the degenerative changes in Ammon's horn.
1968年意外发现海马体能够摄取并留存肾上腺类固醇，这一发现带来了关于激素对大脑的作用以及大脑如何响应激素环境而发生变化的同样意想不到的结果。首先有迹象表明，肾上腺类固醇对海马体的锥体神经元产生不利影响，并在衰老过程中以及由于严重和长期的应激而造成损害。树突萎缩，尤其是在CA3区域，似乎是这些影响的早期指标。其次有证据表明，肾上腺切除术后齿状回会发生萎缩和颗粒神经元死亡；也许是由于这种神经元死亡，成年大鼠齿状回中的神经发生受到刺激。第三，最近有迹象表明，肾上腺类固醇对海马体神经元的兴奋性，包括产生长时程增强（LTP）的能力，具有双相调节作用。当前研究的一个重要目标是了解肾上腺类固醇的I型和II型受体在激素诱导的海马体可塑性中的作用。I型受体似乎在控制程序性细胞死亡和神经发生速率方面发挥作用；它们还调节齿状回和海马角的关键神经化学特征；并且它们促进LTP。目前的信息表明，II型受体抑制LTP，并且可能在海马角的退行性变化中起作用。
