Abstract: Objective To investigate the potential protective effect of miR-326 on brain tissue in depression models. 
Methods A chronic unpredictable mild stress(CUMS)depression model of ratswas established by different types of stress, and miR-326 expression levels were upregulated by miR-326 agomiR injection in the lateral ventricle. Sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and elevated plus maze (EPM) experiments were used to detect the behavioral and depressive states of the animals. The levels of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) in rat serum were measured by enzyme-linked immunosorbent assay （ELISA） kits, and the levels of TLR4 and MyD88 protein expression level in hippocampal tissue of rats were measured by Western blot assay. 
Results The body weight, sucrose consumption, residence time in central region of OFT and open arm time of rats in the CUMS group were lower or less than those in the control group, while the resting time in FST was significantly higher than that in the control group (P＜0.05). Expression of miR-326 in the hippocampal tissues of rats in the CUMS group was significantly lower than that of the control group, which was higher in the hippocampal tissues of rats in the CUMS+agomiR 326 group than in the CUMS+ agomiR NC group (P＜0.05). Body weight, sucrose consumption, residence time in central region of OFT and open arm time were significantly higher in the CUMS+agomiR 326 group than in the CUMS+agomiR NC group, while resting time in FST was significantly lower than that in the CUMS+agomiR NC group (P＜0.05). NE, DA, and 5- HT levels were significantly lower in the CUMS group than in control group, and significantly higher in CUMS+agomiR 326 group than in CUMS+agomiR NC group (P＜0.05). The levels of TLR4 protein and MyD88 protein in rats were significantly higher in CUMS group than in control group, which, however, were significantly lower in CUMS+agomiR 326 group (P＜0.05). 
Conclusion In the CUMS model of depression, miR-326 may exert a protective effect on brain tissue by regulating the TLR4/MyD88 signaling pathway. 

Key words: depression, chronic unpredictable mild stress, microRNAs