心理应激对中枢多巴胺能神经元的影响及酪氨酸的干预作用

Effects of psychological stress on dopaminergic neurous of the central nervous system and the effect of intervention with tyrosine

目的观察反复心理应激对中枢多巴胺(DA)系统的影响及酪氨酸(Tyr)的干预作用。方法用CommunicationBox模型对大鼠进行连续14天、每天30min的心理应激,并经饲料给予250、500、1000mg/kg三个剂量Tyr的干预。应激后对含中脑腹侧被盖区(VTA)、伏隔核(Nac)及前额皮质(mPFC)的脑组织切片进行酪氨酸羟化酶(TH)和Fos蛋白免疫组化染色。结果心理应激组在前囟后5·1mm处VTA部位TH阳性神经元数比正常对照组下降显著(P<0·01);在5·1、5·4、5·7mm处VTA部位,Tyr干预500、1000mg/kg组TH阳性神经元数升高。Fos蛋白在VTA、Nac、mPFC等三个部位均有较强的表达,且心理应激组较对照组明显升高,1000mg/kgTyr干预组较心理应激组明显降低。结论反复心理应激能够损害中枢DA神经元,导致TH阳性神经元数目减少,Fos蛋白表达增加,多巴胺前体物质Tyr的干预能够降低此种损害。

Objective To investigate the effect of repeated psychological stress on central nerve dopamine .system, and the effect of tyrosine intervention. Methods Rats were subjected to psychological stress by Communication Box model continuously for 14 days （30min/d）, and fed with tyrosine in the dose of 250mg/kg, 500mg/kg or 1000mg/kg respectively. Tyrosine hydroxylase （TH） and los protein of the brain tissue in the ventral tegumental area （VTA）, nucleus accumbens （Nac） and mesoprefrontal cortex （mPFC） area were detected by immunohistochemical staining. Results In the ventral tegumental area （VTA）, 5. lmm posterior to anterior fontanel, TH positive neurons were obviously less in number in psychological stress group than that in control group （P〈0. 01 ）. Fos protein immunoreactive substance was highly expressed in VTA, Nac and mPFC. According to density analysis, los protein immunoreactive substance of animals in psychological stress group was significantly higher than that of control group in VTA, Nac and mPFC area, while that of animals of 1000mg/kg tyrosine intervention group was significantly decreased than that of psychological stress group. Conclusion Repeated psychological stress could impair central dopaminergic neurons, inducing a decrease in TH positive neuron and an increase in los protein expression. Tyrosine, the precursor of dopamine may have the effects of reducing this damage.