ABSTRACT
OBJECTIVE To explore the pathogenesis of depression according to the LC-MS/MS-based metabolo?mics in the mouse model which exhibits social avoidance state induced by the chronic social defeat stress model (CSDS). METHODS Twenty male C57BL/6N mice were randomly divided into control group and model group suffering CSDS, and the ICR retired breeder mice were used to attack the model group for 14 d of chronic social defeated stress. The open field test and source preference test were both used to observe depression-like behavior. Besides, the social inter?action test is used to observe the social interaction state, especially. After the stress, the serum samples of mice were collected, and the changes of endogenous metabolites were analyzed by LC-MS metabolomics technology, and the pathway analysis of the differential metabolites was performed to explore the pathogenesis of the CSDS induced depres?sive-like mouse model. RESULTS After the stress of CSDS was completed, the mice in the model group showed a significant slowdown in body weight growth, a reduction in the source preference rate, and a significant reduction in the total distance and the number of rearing in the open field test. Distinctively, the social interaction rate is remarkably decreasing. There are 24 differential metabolites found in the serum of CSDS model mice. CONCLUSION The mouse who suffered CSDS stress would show depressive-like behavior. Based on the LC-MS/MS metabolomics, 24 differential metabolites were found in the serum of CSDS model mice. The amino acid metabolism might be significant to the patho?genesis of the CSDS induced depressive-like mouse model.
ABSTRACT
Objective To establish the Valproate (VPA) exposure-induced autism spectrum disorder (ASD) model at early pregnancy in rats,and to study the changes of social interaction test and neuroimmune system in autism model rats,and discuss the pathogenic mechanism.Methods Twelve-week-old rats were randomly divided into the non-exposed group (n =10) and the VPA-exposed group (n =10).Their babies were respectively just the normal control group (n =10) and the model group (n =10).The autism-like social behavior was evaluated via the social interaction test.The level of interleukin (IL)-1β,IL-4,IL-6,interferon-gamma (IFN-γ),transforming growth factor-beta (TGF-β) in mothers and offspring were detected by using enzyme-linked immunosorbent assay (ELISA).The histopathological damage in brain was observed with immunohistochemical staining.Results The score of social interaction test in the model group [(-163.16 ± 101.92) scores]was lower than that in the normal control group [(132.73 ± 114.63) scores] (t =-6.100,P ＜ 0.05).The levels of IL-1β,IL-4,IL-6,IFN-γ in VPA-exposed group were higher than those in the non-exposed group (t =5.883,6.394,5.655,5.393,all P ＜ 0.05),while the level of TGF-β was lower than that in the non-exposed group (t =-6.726,P ＜ 0.05).The levels of IL-1β,IL-4,IL-6,IFN-γ in the model group were higher than those in the normal control group(t =3.058,3.048,6.670,5.486,all P ＜ 0.05),while the level of TGF-β was lower than that in the normal control group (t =-6.516,P ＜ 0.05).The change trend of the level of cytokines in the serum of ASD model rats was similar to the change trend of the level of cytokines in the serum of VPA exposed rats.The result of social interaction test the approach-avoidance score was inversely correlated with the levels of IL-1β and IL-4 (r =-0.802,-0.781,all P ＜ 0.05).The result of immunohistochemical staining showed the expressions of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA1) in the model group were higher than those in the normal control group.Conclusions The main neuroimmunological pathogenesis mechanism can be explained as follows:at early pregnancy,the maternal cytokines skewing influenced by VPA exposure can make immune activation,induce immune system dysfunction and affect the brain growth and development,which result in autism-like behavior in offspring.
ABSTRACT
The objective of this study was to determine the effect of memantine on schizophrenia-like symptoms in a ketamine-induced social withdrawal model in rats. We examined therapeutic effects of memantine, an NMDA antagonist, and haloperidol, a classic antipsychotic drug, on this behavioral model. Administration of memantine (10 or 15 mg.kg(-1)) significantly reduced ketamine-induced social withdrawal, and this effect was more effective than that of haloperidol (0.25 mg.kg(-1)) by restoring the social interaction between rats with no modification in general motor activity. These results suggest that memantine could have a therapeutic potential for schizophrenia.