| BackgroundEpilepsy and depression affect each other in neurobiology,and the relationship between them is complex and close.The prefrontal cortex,hippocampus and amygdala are important brain regions closely related to epilepsy and depression.Current studies have found that microglia are involved in the pathogenesis of epilepsy and depression.Type M1 microglia cells have pro-inflammatory effect,and type M2 microglia cells have anti-inflammatory effect.Epileptic seizure or chronic depression stimulation can induce increased expression of i NOS phenotypic marker in M1-type microglia and decreased expression of Arg-1 phenotypic marker in M2-type microglia.However,no systematic study has been reported on the role of i NOS and Arg-1 in epileptic comorbid depression.This experiment aims to by immunohistochemical staining method and TUNEL in situ end labeling method to detect epilepsy comorbid depression rat frontal cortex,hippocampus and the amygdala region before the expression of i NOS and Arg-1 and neurons apoptosis,affective disorder comorbid depression rats epilepsy related brain regions of i NOS,Arg-1 protein expression differences and neurons apoptosis,to explore the role of microglia in epilepsy comorbid depression provide preliminary basis.ObjectiveThe expression of i NOS and Arg-1 protein and the apoptosis of nerve cells in the prefrontal cortex,hippocampus and amygdala of the rats with epileptic comorbidities depression were detected to understand the role of different activation types of microglia in the brain regions associated with affectional disorders in the pathogenesis of epileptic comorbidities depression.MethodsLithium chloride-pilocarpine method was used to establish the epileptic rat model.On the 14 th day after modeling,the depressive behavior score of the model rats was conducted.According to the score results,the rats with depression were selected as the epileptic comorbidities depression group(comorbidity group).Patients without depression were in the epilepsy group.The depression group was established by Chronic Unpredictable Mild Stress(CUMS)combined with solitary confinement.Meanwhile,normal control group was set,with 5 rats in each group.The depressive behavior score was performed once a week in each group.Immunohistochemistry and TUNEL in situ end labeling were performed at the 4th weekend of CUMS to detect the expression of i NOS and Arg-1 protein in the prefrontal cortex,hippocampus and amygdala and the apoptosis of neuronal cells in each group.ResultsResults of depressive behavior indicators: compared with the normal group and the epilepsy group,the body mass index,sucrose preference rate,horizontal and vertical movement of rats in the epilepsy comorbidities depression group were significantly decreased,with statistical significance(all P < 0.05).Compared with the depression group,the sucrose preference rate and horizontal movement of rats in the epileptic comorbid depression group were significantly decreased(all P < 0.05).The results of immunohistochemical staining showed: compared with the control group,the mean optical density of i NOS in prefrontal cortex,hippocampus and amygdala of rats in the experimental group was significantly increased(all P <0.05).The average optical density of Arg-1 was significantly decreased(all P <0.05).Comparison of i NOS and Arg-1 in different brain regions in the epileptic comorbidities depression group: the average optical density of i NOS in the hippocampus of the experimental group was significantly higher than that in the prefrontal cortex and amygdala(all P < 0.05).The average optical density of Arg-1 in hippocampus and prefrontal cortex was higher than that in amygdala(all P < 0.05).Arg-1 was not significantly different in hippocampus and prefrontal cortex(P>0.05).TUNEL staining results: Compared with the control group,the number of TUNEL positive cells in the prefrontal cortex,hippocampus and amygdala of rats in the experimental group was significantly increased(all P < 0.05).Comparison of TUNEL positive cells in different brain regions in the epileptic comorbidities depression group:the number of TUNEL positive cells in the hippocampus of the experimental group was significantly higher than that in the prefrontal cortex and amygdala(all P < 0.05).ConclusionLithium chloride-pilocarpine can successfully induce epileptic comorbiditic depression model.The activation of M1-type(pro-inflammatory)microglia in the prefrontal cortex,hippocampus and amygdala in the affective disorder brain regions of rats with epileptic comorbidities depression increased,while the activation of M2-type(anti-inflammatory)microglia decreased,and the number of apoptotic nerve cells increased.Compared with prefrontal cortex and amygdala,the activation and apoptosis of M1-type microglia in hippocampus of rats with epileptic comorbidities depression were significantly increased,which may play a greater role in the pathogenesis of epileptic comorbidities depression. |
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