Behavioural Neuroscience Group, School of Psychology, University of Ottawa, 136 Jean-Jacques Lussier, Ottawa, ON, K1N 6N5, Canada.
Behavioural Neuroscience Group, School of Psychology, University of Ottawa, 136 Jean-Jacques Lussier, Ottawa, ON, K1N 6N5, Canada; University of Ottawa Institute of Mental Health Research (IMHR), 1145 Carling Avenue Ottawa, Ontario K1Z 7K4, Canada.
Horm Behav. 2014 Mar;65(3):273-84. doi: 10.1016/j.yhbeh.2014.01.003. Epub 2014 Jan 17.
Abnormal function of the neuroendocrine stress system has been implicated in the behavioral impairments observed following brain ischemia. The current study examined long-term changes in stress signal regulation 30days following global cerebral ischemia. Experiment 1 investigated changes in the expression of corticotropin releasing hormone (CRH) and its subtype 1 receptor (CRHR1), glucocorticoid receptors (GR) in the paraventricular nucleus of the hypothalamus (PVN), the central nucleus of the amygdala (CeA), and the CA1 subfield of the hippocampus. Tyrosine hydroxylase (TH) was determined at the locus coeruleus (LC). Experiment 2 investigated the role of central CRHR1 activation on corticosterone (CORT) secretion at multiple time intervals following global ischemia after exposure to an acute stressor. Findings from Experiment 1 demonstrated a persistent increase in GR, CRH and CRHR1 immunoreactivity (ir) at the PVN, reduced GR and CRHR1 expression in pyramidal CA1 neurons, and increased LC TH expression in ischemic rats displaying working memory errors in the radial arm Maze. Findings from Experiment 2 revealed increased CORT secretion up to 7 days, but no longer present 14 and 21 days post ischemia. However upon an acute restraint stress induced 27 days following reperfusion, ischemic rats had increased plasma CORT secretions compared to sham-operated animals, suggesting HPA axis hypersensitivity. Antalarmin (2 μg/2 μl) pretreatment significantly attenuated post ischemic elevation of basal and stress-induced CORT secretion. These findings support persistent neuroendocrine dysfunctions following brain ischemia likely to contribute to emotional and cognitive impairments observed in survivors of cardiac arrest and stroke.
神经内分泌应激系统的异常功能与脑缺血后观察到的行为障碍有关。本研究检测了全脑缺血后 30 天应激信号调节的长期变化。实验 1 研究了促肾上腺皮质激素释放激素 (CRH)及其亚型 1 受体 (CRHR1)、糖皮质激素受体 (GR)在下丘脑室旁核 (PVN)、杏仁中央核 (CeA)和海马 CA1 亚区的表达变化。酪氨酸羟化酶 (TH)在蓝斑核 (LC)中测定。实验 2 研究了在暴露于急性应激后，全脑缺血后多个时间点中枢 CRHR1 激活对皮质酮 (CORT)分泌的作用。实验 1 的结果表明，GR、CRH 和 CRHR1 免疫反应性 (ir) 在 PVN 持续增加，CA1 锥体神经元中的 GR 和 CRHR1 表达减少，缺血大鼠 LC TH 表达增加，在放射臂迷宫中表现出工作记忆错误。实验 2 的结果显示，CORT 分泌增加至 7 天，但缺血后 14 天和 21 天不再存在。然而，在再灌注后 27 天急性束缚应激诱导后，缺血大鼠的血浆 CORT 分泌量比假手术动物增加，表明 HPA 轴超敏。安他拉明 (2 μg/2 μl) 预处理可显著减弱缺血后基础和应激诱导的 CORT 分泌升高。这些发现支持脑缺血后持续存在的神经内分泌功能障碍，可能导致心脏骤停和中风幸存者中观察到的情绪和认知障碍。
