The HPA and immune axes in stress: the involvement of the serotonergic system
The HPA and immune axes in stress: the involvement of the serotonergic system
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DOI：
10.1016/s0924-9338(05)80180-4
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发表时间：
2005-10-01
影响因子：
7.8
通讯作者：
Leonard, BE
中科院分区：
文献类型：
--
作者：
Leonard, BE
本文综述了急性和慢性应激对下丘脑-垂体-肾上腺（HPA）轴的影响，并提出促肾上腺皮质激素释放因子（CRF）是应激神经递质，在中枢交感神经系统和雌激素系统的激活中起重要作用。CRF的活性通过特异性受体表达（CRF 1和2），其作用是拮抗的，并且广泛分布在大脑的边缘区域，以及下丘脑和免疫细胞上。慢性应激通过CRF诱导中缝背核的激活，可以诱导多巴胺能系统的变化的机制，涉及5 HT 2A的增加和5 HT 1A受体介导的功能的降低。这些变化会导致焦虑和抑郁的发作。此外，与慢性应激和抑郁相关的糖皮质激素分泌过多使中枢糖皮质激素受体对HPA轴的负反馈抑制脱敏。这间接导致HPA轴的进一步激活。通常伴随慢性应激反应的促炎细胞因子的升高导致HPA轴的进一步刺激，从而增加应激反应。虽然CRF似乎发挥了关键作用，但有证据表明，肾上腺素能和去甲肾上腺素能系统的同时变化，以及外周和中枢巨噬细胞的活化，增加了大脑和血液中的促炎细胞因子浓度，也在诱发焦虑和抑郁中发挥了关键作用。在患有重度抑郁症的老年患者中经常发生的脑中的神经退行性变化可能是由吲哚胺双加氧酶（IDO）的激活引起的，IDO是一种广泛分布的酶，其通过kynenine途径将色氨酸转化为神经毒性终产物喹啉酸。(c)2005年，Elsevier SAS。All rights reserved.
The impact of acute and chronic stress on the hypothalamic-pituitary-adrenal (HPA) axis is reviewed and evidence presented that corticotrophin releasing factor (CRF) is the stress neurotransmitter which plays an important role in the activation of the central sympathetic and scrotonergic systems. The activity of CRF is expressed through specific receptors (CRF 1 and 2) that are antagonistic in their actions and widely distributed in the limbic regions of the brain, as well as in the hypothalamus, and on immune cells.The mechanism whereby chronic stress, via the CRF induced activation of the dorsal raphe nucleus, can induce a change in the serotonergic system, involves an increase in the 5HT2A and a decrease in the 5HT1A receptor mediated function. Such changes contribute to the onset of anxiety and depression. In addition, the hypersecretion of glucocorticoids that is associated with chronic stress and depression desensitises the central glucocorticoid receptors to the negative feedback inhibition of the HPA axis. This indirectly results in the further activation of the HPA axis.The rise in pro-inflammatory cytokines that usually accompanies the chronic stress response results in a further stimulation of the HPA axis thereby adding to the stress response. While CRF would appear to play a pivotal role, evidence is provided that simultaneous changes in the serotonergic and noradrenergic systems, combined with the activation of peripheral and central macrophages that increase the pro-inflammatory cytokine concentrations in the brain and blood, also play a critical role in predisposing to anxiety and depression. Neurodegenerative changes in the brain that frequently occur in the elderly patient with major depression, could result from the activation of indoleaminedioxygenase (IDO), a widely distributed enzyme that converts tryptophan via the kynenine pathway to for the neurotoxic end product quinolinic acid. (c) 2005 Elsevier SAS. All rights reserved.