Peripheral Blockade Of LC/NE-Sympathetic System Induced Brain Protection And Damage In CUMS Rats

Objective To investigate the effects of adrenergic receptor antagonist, phentolamine and propranolol,on open-field behavior,serum concentrations of cortisol and interleukin-6 and expression of inducible heat shock protein 70 and inducible nitric oxide synthase in different brain areas of chronic-stressed rats;to study the interactions that occurred among the nervous,endocrine and immune systems during chronic unpredictable mild stress;to explore the brain protection and damage in chronic-stressed rats induced by peripheral blockade of locus ceruleus-norepinephrine sympathetic system.Methods Thirty-two adult male Wistar Rats were randomly divided into four groups:the non-stress group,the model group,the phentolamine group and the propranolol group,with eight ones in each group.All rats of the latter three groups received 21 days of chronic unpredictable mild stress.Rats in the latter two groups received intraperitoneal injection of phentolamine(Smg/kg)or propranolol(10mg/kg) 30 minutes prior to each stressful stimulus.At the end of the experiment,all rats' open-field activities were investigated.Concentrations serum cortisol and interleukin-6 were measured using radioimmunoassays.Brain tissues including prefrontal lobe,corpus striatum and hippocampus were reserved and made into paraffin sections.Immunohistochemistry staining was adopted for detection of inducible heat shock protein 70 and inducible nitric oxide synthase. Hematoxylin-eosin Staining was used to study morphological changes in the brain areas mentioned above.Results1.Compared with the non-stress group,serum concentrations of cortisol and interleukin-6 were significantly elevated in rats of the model group and the propranolol group.In rats of the phentolamine group only inteleukin-6 level was elevated.2.Significant elevated expression of inducible heat shock protein 70 was observed in all studied brain areas of rats in the model group,with prefrontal cortex showed most obvious elevation.All studied brain areas of rats in the phentolamine group showed increased inducible heat shock protein expression,except for the prefrontal cortex.What's more,the dentate gyrus subfield of hippocampus showed even higher expression than that of the model group.All studied brain areas of rats in the propranolol group showed increased inducible heat shock protein expression, compared with that of the control group and the model group.Expression level of inducible nitric oxide synthase in the dentate gyrus subfield of hippocampus of rats in the model group and the phentolamine group was significant higher than that of the control group and lower than that of the propranolol group.CA3 subfield of hippocampus of rats in the propranolol group also showed obviously increased inducible nitric oxide synthase expression.3.CA3 and dentate gyrus subfields of hippocampus of rats of the model group exhibited disturbed cell alignment,increased intercellular space,cell atrophy and deformity and chromatin condensation.Prefrontal cortex and corpus striatum also showed decreased cell number and volume.Changes in the prefrontal cortex and hippocampus in rats of the phentolamine group and the propranolol group were basically similar to that of the model group.Damage in corpus striatum can be observed in rats of the model group and is more severe in the propranolol group,but was not obvious in the rats of the phentolamine group.4.In the open-field test,significantly decreased crossings,rearings and groomings and increased time spent in the center squares were observed in rats of the model group and the propranolol group.No significant discrepancy was found between rats of the control group and the phentolamine group.Conclusion1.α-adrenergic receptor antagonist phentolamine helped suppress serum cortisol upregulation,behavioral changes and damage in prefrontal,corpus striatum and hippocampus and in chronic-stressed rats.2.β-adrenergic receptor antagonist propranolol showed protective effects on prefrontal and hippocampus in chronic-stressed rats,but was found to enhance the damage of stress to corpus striatum.3.Immune system may participate in the initiation of stress response and play a role in maintaining the chronic stress induced malfunction of neuroendocrine system.