α2A and α2C-adrenoceptor regulation in the brain:: α2A changes persist after chronic stress
α2A and α2C-adrenoceptor regulation in the brain:: α2A changes persist after chronic stress
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DOI：
10.1046/j.1460-9568.2003.02510.x
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发表时间：
2003-03-01
影响因子：
3.4
通讯作者：
Fuchs, E
中科院分区：
文献类型：
--
作者：
Flügge, G;van Kampen, M;Fuchs, E
应激诱导的中枢神经去甲肾上腺素能系统的激活被怀疑会诱发抑郁症。由于抑郁症的发作通常发生在压力经历后一段时间，我们研究了压力诱导的α（2）-肾上腺素受体（α（2）-AR）系统的变化是否在压力后恢复期持续存在。在44天的慢性心理社会压力和随后的10天恢复期后，对雄性树鼩的大脑进行了分析。通过原位杂交定量α（2A）和α（2C）-肾上腺素受体的RNA表达，并通过体外受体放射自显影测定受体结合。交感神经系统和下丘脑-垂体-肾上腺轴的活动在慢性应激期间增加，但在恢复期间恢复正常。应激后和恢复后，外侧网状核内海马能神经元α（2A）-AR RNA显著升高（分别为29%和17%）。在迷走神经背侧运动核中，恢复后A亚型表达增强（33%）。在蓝斑，亚型A自身受体的表达没有显着变化。在尾状核和壳核的亚型C表达升高的压力（分别为5%和4%），但在恢复正常。H-3-RX 821002结合的定量揭示了应激和/或恢复期间受体上调。因此，我们的数据显示：（i）慢性心理社会应激差异调节α（2）-肾上腺素受体亚型A和C的表达;（ii）亚型A异源受体表达持续上调，而（iii）亚型C上调仅是短暂的。目前的研究结果与抑郁症患者的尸检研究一致，揭示了α（2A）-AR的上调。
Stress-induced activation of the central nervous noradrenergic system has been suspected to induce depressive disorders. As episodes of depression often occur some time after a stress experience we investigated whether stress-induced changes in the alpha(2)-adrenoceptor (alpha(2)-AR) system persist throughout a post-stress recovery period. Brains of male tree shrews were analysed after 44 days of chronic psychosocial stress and after a subsequent 10-day recovery period. Expression of RNA for alpha(2A) and alpha(2C)-adrenoceptors was quantified by in situ hybridization, and receptor binding was determined by in vitro receptor autoradiography. Activities of the sympathetic nervous system and of the hypothalamo-pituitary-adrenal axis were increased during chronic stress but normalized during recovery. alpha(2A)-AR RNA in the glutamatergic neurons of the lateral reticular nucleus was elevated significantly after stress and after recovery (by 29% and 17%). In the dorsal motor nucleus of the vagus, subtype A expression was enhanced after recovery (by 33%). In the locus coeruleus, subtype A autoreceptor expression was not changed significantly. Subtype C expression in the caudate nucleus and putamen was elevated by stress (by 5 and 4%, respectively) but normalized during recovery. Quantification of H-3-RX821002 binding revealed receptor upregulation during stress and/or recovery. Our data therefore show: (i) that chronic psychosocial stress differentially regulates expression of alpha(2) -adrenoceptor subtypes A and C; (ii) that subtype A heteroreceptor expression is persistently upregulated whereas (iii), subtype C upregulation is only transient. The present findings coincide with post mortem studies in depressed patients revealing upregulation of alpha(2A)-ARs.