Magariños A M, McEwen B S
Laboratory of Neuroendocrinology, Rockefeller University, New York, N.Y. 10021, USA.
Neuroscience. 1995 Nov;69(1):83-8. doi: 10.1016/0306-4522(95)00256-i.
Repeated restraint stress induces an atrophy of apical dendrites of CA3c pyramidal neurons in the hippocampus, but the relationship between stress and adrenocortical activation has not been thoroughly investigated. In order to better understand the relationship between neural and non-neural indices of the severity of stress, we investigated the temporal relationship between CA3c dendritic atrophy and indices of adrenal steroid stress responsiveness. For this purpose, we used two different stress regimens: repeated restraint stress (6 h/day) and a chronic multiple stress paradigm (shaking, restraint and swimming, each day), differing in the degree of adrenal activation produced over 14 and 21 days. Atrophy of dendrites of CA3c neurons was found after 21 days of stress, but not after 14 days, and was of a similar magnitude for both stressors. However, non-neural measures differed between the two stress paradigms: (i) chronic restraint stress caused a significant habituation by day 21 in the corticosterone response to acute restraint, whereas chronic multiple stress exposure was not accompanied by habituation of the corticosterone response to restraint; (ii) chronic restraint stress caused neither adrenal hypertrophy nor thymus atrophy, but did reduce the rate of body weight gain throughout the 21 days, whereas chronic multiple stress caused a transient adrenal hypertrophy (on day 14), delayed suppression of thymus weight (on day 21) and transient reduction of body weight gain (on days 7 and 14, but not on day 21). Thus the non-neural indices of response to stress--although complex in their time course--suggest that the multiple stress regimen is a somewhat more potent chronic stressor for corticosterone and adrenal responses. Yet both stress regimens produced the same degree of apical dendritic atrophy in CA3c pyramidal neurons. These results are consistent with a model in which adrenocortical secretion plays a permissive role in enabling another agent, namely, excitatory amino acids, to produce the final effect.
反复束缚应激会导致海马体中CA3c锥体神经元顶树突萎缩，但应激与肾上腺皮质激活之间的关系尚未得到充分研究。为了更好地理解应激严重程度的神经和非神经指标之间的关系，我们研究了CA3c树突萎缩与肾上腺类固醇应激反应指标之间的时间关系。为此，我们采用了两种不同的应激方案：反复束缚应激（每天6小时）和慢性多重应激范式（每天摇晃、束缚和游泳），这两种方案在14天和21天内产生的肾上腺激活程度不同。应激21天后发现CA3c神经元树突萎缩，而14天后未发现，且两种应激源导致的萎缩程度相似。然而，两种应激范式的非神经指标有所不同：（i）慢性束缚应激在第21天时导致皮质酮对急性束缚的反应出现显著的适应性变化，而慢性多重应激暴露并未伴随皮质酮对束缚反应的适应性变化；（ii）慢性束缚应激既未导致肾上腺肥大，也未导致胸腺萎缩，但在整个21天内确实降低了体重增加率，而慢性多重应激则导致短暂的肾上腺肥大（在第14天）、胸腺重量延迟抑制（在第21天）和体重增加短暂减少（在第7天和第14天，但在第21天未出现）。因此，应激反应的非神经指标——尽管其时间进程复杂——表明多重应激方案对皮质酮和肾上腺反应而言是一种更强效的慢性应激源。然而，两种应激方案在CA3c锥体神经元中产生的顶树突萎缩程度相同。这些结果与一种模型一致，即肾上腺皮质分泌在使另一种物质（即兴奋性氨基酸）产生最终效应方面发挥允许作用。
