| ObjectiveDepression in patients with epilepsy aggravates the severity of the disease and increases the social burden.However,the mechanism between the two is still unclear.This study intends to compare the differences between epilepsy-related depression and primary depression,to study the cell morphology of the Midbrain Periaqueductal Gray(PAG)area,to study the expression of 5-hydroxytryptamine(5-HT),Galanin(GAL)Brain-derived neurotrophic factor(BDNF)and tropo-myosin-related kinase B(TrkB)in midbrain aqueduct of epilepsy with depression rats.MethodsRats were divided into normal control group(Control group),epilepsy without depression group(Epilepsy group),and epilepsy with depression group(Comorbid group).Lithium pilocarpine-induced chronic epilepsy rat model was established.Depression group used Chronic unpredictable mild stress(CUMS)depression model as a positive control.Forced swim test(FST)and sucrose consumption test(SCT)are two behavioral experiments to screen rats with depressive behaviors.At the 1st,8th,15 th and 28 th day,the body weight,sucrose water consumption test and Immobility time(IMT),were monitored to evaluate the depressive behavior.HE staining and Nissl staining were used to observe the pathological changes of nerve cells in PAG region of rats.ELISA was used to observe the changes of 5-HT and BDNF in serum.Immunohistochemical staining was used to observe the changes of GAL and 5-HT expression levels in PAG region.Immunofluorescence staining and Western blot were used to detect the expression levels of BDNF and TrkB in the PAG region of rats with epilepsy and depression.ResultAfter the fourth week of the aforementioned behavioral test,it was found that the rats’ body weight was reduced,the consumption of sucrose solution was reduced,and the immobility time of the forced swimming experiment was prolonged.On the 28 th day after CUMS,the above indexes of rats in the Comorbid group and the Depression group were significantly different from those of 1,8,and 15 days after modeling.(2)The damaged neurons in the PAG area in the Comorbid group,the Depression group and Epilepsy group showed shrunken and hyperchromatic cells with scattered Nissl bodies.The damage in the Comorbid group was more obvious than that in Epilepsy group.(3)Compared with the Control group,the 5-HT concentration in the serum of the Epilepsy group,the Depression group and the Comorbid group was lower,and the concentration of BDNF in the serum of the Depression group and the Comorbid group was lower;compared with the Epilepsy group,the 5-HT in the serum of the Depression group and the Comorbid group was lower.The concentrations of 5-HT and BDNF were low;there was no significant difference between the Comorbid group and the Depression group.(4)GAL and 5-HT were expressed in the four groups of PAG regions.Compared with the Control group,GAL and 5-HT positive cells in the PAG area of Epilepsy group,Depression group,and Comorbid group increased;compared with the Epilepsy group,the GAL and 5-HT positive cells in the PAG area of the Depression group and Comorbid group decreased;There was no significant difference between Comorbid group and Depression group.(5)BDNF and TrkB were expressed in the PAG area of the four groups.Compared with the Control group,the two positive cells of BDNF and TrkB in the PAG area of the Depression group and Comorbid group were reduced,the number of BDNF and TrkB positive cells in the PAG area of the Epilepsy group were increased;compared with the Epilepsy group,the numbers of BDNF and TrkB positive cells in the PAG area of rats in the Depression group and Comorbid group were decreased;there was no statistical significance between the Comorbid group and the Depression group.(6)Compared with the Control group,the expression levels of BDNF and TrkB in the PAG area of rats in the Depression group and Comorbid group were lower,and the expression levels of BDNF and TrkB in the PAG area of rats in the Epilepsy group were increased;compared with the Epilepsy group,the expression levels of BDNF and TrkB in PAG area of rats in Depression group and Comorbid group were lower;there was no statistical significance between Comorbid group and Depression group.ConclusionThe lithium pilocarpine rat model of chronic epilepsy is helpful to study the complications of epilepsy and depression.The occurrence and development of epilepsy associated with depression induce dysfunction and structural changes of neurons in PAG area,which indicates that PAG is affected by the occurrence and development of epilepsy and depression.The neuromodulator 5-HT and neuropeptide GAL in the PAG area may be involved in the pathophysiological process of epilepsy comorbid depression.The dysfunction of BDNF-TrkB signal in PAG area is associated with epilepsy comorbid depression. |
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