STRESS-INDUCED ATROPHY OF APICAL DENDRITES OF HIPPOCAMPAL CA3C NEURONS - INVOLVEMENT OF GLUCOCORTICOID SECRETION AND EXCITATORY AMINO-ACID RECEPTORS
STRESS-INDUCED ATROPHY OF APICAL DENDRITES OF HIPPOCAMPAL CA3C NEURONS - INVOLVEMENT OF GLUCOCORTICOID SECRETION AND EXCITATORY AMINO-ACID RECEPTORS
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DOI：
10.1016/0306-4522(95)00259-l
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发表时间：
1995-11-01
期刊：
影响因子：
3.3
通讯作者：
MCEWEN, BS
中科院分区：
文献类型：
--
作者：
MAGARINOS, AM;MCEWEN, BS
大鼠21天反复束缚应激导致海马CA3c锥体神经元顶树突萎缩。这种效果可以通过连续 21 天的每日皮质酮治疗来模拟，并且可以通过抗癫痫药物苯妥英来预防，苯妥英已知会干扰兴奋性氨基酸的释放和作用。本研究旨在探讨内源性皮质酮分泌和兴奋性氨基酸受体在应激诱导的海马树突萎缩中的作用。用类固醇合成阻滞剂氰酮治疗长期应激的大鼠可预防应激引起的树突萎缩。经过氰酮处理的动物表现出对应激源的反应受损的皮质酮分泌，但基础水平得以维持。除了参与内源性皮质酮分泌外，N-甲基-D-天冬氨酸受体也发挥作用，因为竞争性受体拮抗剂 CGP 43487 可以阻止应激诱导的树突萎缩。相比之下，NBQX（一种α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体的竞争性抑制剂）在阻断缺血性损伤的剂量下无效。这些结果表明，21天的日常束缚应激诱导的可逆性萎缩需要皮质酮分泌，并且涉及N-甲基-D-天冬氨酸的兴奋机制 受体在驱动萎缩中起主要作用。
Repeated restraint stress of rats for 21 days causes atrophy of apical dendrites of hippocampal CA3c pyramidal neurons. This effect, is mimicked by daily corticosterone treatment for 21 days and is prevented by the anti-epileptic drug, phenytoin, known to interfere with excitatory amino acid release and action. The present study was designed to investigate the involvement of endogenous corticosterone secretion and excitatory amino acid receptors in the stress-induced hippocampal dendritic atrophy. Treatment of chronically stressed rats with the steroid synthesis blocker cyanoketone prevented stress-induced dendritic atrophy. Cyanoketone-treated animals showed an impaired corticosterone secretion in response to the stressor, while basal levels were maintained. Besides the involvement of endogenous corticosterone secretion, N-methyl-D-aspartate receptors also play a role, since the competitive receptor antagonist, CGP 43487, blocked stress-induced dendritic atrophy. In contrast, NBQX, a competitive inhibitor of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, was ineffective at a dose that blocks ischemic damage.These results indicate that the reversible atrophy induced by 21 days of daily restraint stress requires corticosterone secretion and that excitatory mechanisms involving N-methyl-D-aspartate receptors play a major role in driving the atrophy.