二、52HT系统与皮质激素在抑郁症中的作用
慢性应激是造成抑郁症的重要原因之一,慢性应激可以造
成皮质激素水平升高,海马不仅是应激毒性效应最敏感的区
域,而且皮质激素受体密集,因此很多研究者认为高水平皮质
激素是造成抑郁症的主要生化基础。但是持续的慢性应激也
导致了52HT系统的功能紊乱,如52HT合成减少, 52HT1A受体
敏感性失调, 52HT2A受体超敏等。同时, 52HT2受体调节下丘脑2
垂体2肾上腺轴( hypothalamo2p ituitary2adrenal axis, HPA轴)的活
性,局部应用52HT2A受体拮抗剂能降低由性刺激引起的下丘脑
激素的应答,并且52HT系统的紊乱对海马的损害也使海马对
HPA轴的负反馈受损,导致皮质激素水平升高。在海马和海马
细胞培养中, 52HT7受体可调节糖皮质激素受体的活性。在某
些抑郁症患者中,地塞米松实验并不敏感,甚至脑脊液中CRH
水平下降,但52HT系统传导低下。并且,在急性应激期和连续
昼夜工作后,糖皮质激素也会增高,因此,糖皮质激素的增高可
能只是应激状态的一种现象,并不一定是造成抑郁症的生理病
理基础。抗抑郁治疗中,很多有效的抗抑郁治疗主要是针对52
HT系统的功能紊乱,虽然糖皮质激素受体mRNA也会增高,但
只是一个次要因素,随着病情的好转它也会逐渐恢复正常[ 15 ]。
另外,BDNF是抗抑郁中的一个重要因子,而应用皮质激素对
CA1 和CA3 区BDNFmRNA的生成毫无影响,只是齿状核区的
BDNFmRNA稍微减少,肾上腺切除也并不能阻断齿状核的BD2
NF下调,但是具有52HT2A受体拮抗活性的药物可以阻断BDNF
下调。因此,皮质激素高水平可能并不是造成抑郁症的主要生
理病理基础,只是一个现象或应激指标,而52HT系统功能紊乱
可能是导致抑郁症的直接原因之一。
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(收稿日期: 2005 - 05 - 31)
(本文编辑:冯学泉)
·380· 中国行为医学科学2006年4月第15卷第4期 Chin J of BehavioralMed Sci,Ap ril 2006,Vol 15,No. 4作者: 新生的雪儿 时间: 10-5-1 00:47
谢谢！！！作者: WINTER1137 时间: 10-5-1 06:49
我讨厌海马作者: zangma 时间: 10-5-1 07:48
不错很专业作者: 继续研究 时间: 10-5-1 11:04
单相刺激海马5-ht受体和肾上腺素受体可能会导致受体在超敏-超钝间摆动,
导致情绪双相变化,其实单研究抑郁不如研究双相障碍更容易对比这些疾病的机制