The Effects And Neuroendocrine Mechanism Of Chronic Anger Stress On Rats' Brain Aging

Objective: To observe the ethology, oxidative function, and neuroendocrine (hypothalamus-pituitary-adrenal axis) made by the chronic anger stress on the rats with brain aging induced by D-galactose(D-gal), and discuss the effects and mechanism of chronic anger stress on rats'brain aging for providing the evidence of etiology and animal experiments. The study can provide new knowledge and experimental evidence for the emotion theory of Chinese medicine of"the liver facilitating the flow of qi","the liver regulating emotion","internal injury caused by seven emotions"and so on.Methods: Fifty-six Wistar male rats (SPF:3-month-old)were involved, the weight was 360±10g, which were randomly divided into the blank control group, D-gal aging and brain aging model group(for short model group), chronic angry stress group(for short angry stress group). There were 14 rats in every group and the others were the rats with aggression. The rats in the model group and angry stress group were given continuously subcutaneous injection of high dose D-galactose on the nape for 6 weeks in order to make aging and brain aging animal model. Since the third weeks, the rats in the angry stress group were given indirectly electric shock for inducing the rats'angry stress. The change of rats'spatial learning and memory in every group were observed by Morris water maze from day 37 to day 42, the rats'ethology in each group were observed by open field test at day 42 compared with the basic level of this test. At day 43 the samples were taken and the following indexes were detected:①oxidation and antioxidation capacity: plasma malondialdehyde (MDA), plasma superoxide dismutase (SOD);②the level of plasma hormones: adrenocorticotrophic hormone(ACTH), corticosterone (CORT);③plasma monoamine neurotransmitters: noradrenaline (NE), 5-hydroxytryp-tamine(5-HT), dopamine(DA);④mitochondrial membrane potential(MMP), the percentage of hippocampal neurons apoptosis;⑤the microcosmic structure hippocampal neurons.Results:1 The rats'model of brain aging induced by D-gal is established successfully.2 Compared with the model group, The SPL of angry stress group increased significantly.3 Compared with the model group, the content of MDA in plasma in the angry stress group increased significantly, the content of SOD in plasma in the angry stress group decreased substantially.4 Compared with the model group, the content of ACTH and CORT in plasma in the angry stress group increased significantly.5 Compared with the model group, the content of NE and DA in plasma in the angry stress group increased significantly, the content of 5-HT in plasma in the angry stress group decreased substantially.6 Compared with the model group, the percentage of hippocampal neurons apoptosis in the angry stress group increased significantly.7 Compared with the model group, the mimetic aging change in hippocampal neurons in the angry stress group was more common.Conclusions:1 Because of long-term accumulation of anger, the rats'spatial learning and memory was lowered, the rats'brain aging was aggravated. Chronic anger stress may be one of reasons to accelerate the brain aging process by inference.2 The mechanism of the process of brain aging accelerated by chronic anger stressmay be:(1) Aggravating the lipid peroxidation of the body, and lowering anti-oxidation function of the body.(2) Activating hypothalamus - pituitary - adrenal axis, and affecting the level of neurotransmitters.(3) Raising the proportion of hippocampal neurons apoptosis.(4) Aggravating mimetic aging change of hippocampal neurons apoptosis.