Effects of Chaijin Jieyu Anshen Tablets on synaptic injury of anterior cingulate cortex neurons in depressed rats via GR/CX3CR1 signaling
AIM To explore the protective effects of Chaijin Jieyu Anshen Tablets on synaptic damage of neurons in anterior cingulate cortex (ACC) of depressed rats mediated by glial glucocorticoid receptor/chemokine receptor 1 (GR/CX3CR1).METHODS 28 days after their induction into depression models by chronic unpredictable mild stress (CUMS),the rats were then randomly divided into the model group,the GR blocker group (10 μmol/L RU486),the CX3CR1 blocker group (50 nmol/L AZD8797),the venlafaxine group (13.5 mg/kg) and the Chaijin Jieyu Anshen Tablets group (5.68 g/kg),with 7 rats in each group,in contrast to the other 7 normal rats given normal feeding.After 28 days drug administration,the rats had their depression-like behaviors evaluated by water maze,open field and forced swimming experiments combined with animal behavior analysis system;their morphological and structural changes of neurons in ACC brain region detected by HE staining;their levels of corticotropin (ACTH),corticotropin-releasing hormone (CRH),corticosterone (CORT),tumor necrosis factor α(TNF-α),interleukin-1β(IL-1β),interleukin-6 (IL-6) and glutamic acid (Glu) in serum and cerebrospinal fluid detected by ELISA;their expressions of GR,glutamate transporter 1 (VGluT1),CX3CR1 and adenosine receptor A2a (A2AR) detected by immunofluorescence and Western blot respectively;and their damage of dendrites,dendritic spines and synapses in ACC brain area detected by Golgi staining.RESULTS Compared with the model group,the group intervened by Chaijin Jieyu Anshen Tablets displayed effectively improved depression-like behaviors in water maze,open field and forced swimming experiments (P<0.05,P<0.01);repaired morphological damage of neurons in ACC brain tissue,inhibited abnormal increase of neuroendocrine related factors ACTH,CRH,CORT and neuroimmune related factors TNF-α,IL-1β,IL-6 and Glu in serum and cerebrospinal fluid (P<0.05,P<0.01);down-regulated expressions of GR/CX3CR1 dual signal-related proteins GR,CX3CR1 and A2AR in glial cells (P<0.05,P<0.01);up-regulated expression of VGluT1 protein (P<0.01);and reduced damage of dendrites,dendritic spines and synaptic structures in ACC neurons.CONCLUSION Chaijin Jieyu Anshen Tablets may relieve the depressive-like behaviors in rats through the alleviation of the synaptic damage of ACC neurons via glial cells GR/CX3CR1 signaling,and this crucial molecular mechanism may highlight the the prevention and treatment of depression.
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