Effects of long-term injection of corticosterone on hippocampal astrocytes and synaptic plasticity in mice

Objective To study the effects of long-term injection of corticosterone (CORT) on the hippocampal astrocytes and synaptic plasticity in mice. Methods Male C57BL/6N mice (n=40) were randomly divided into control group and model group.Mice in the model group were treated with subcutaneous injection of CORT for 4 weeks to generate chronic stress depression model. Chronic stress model was proved to be established by tail suspension test and sucrose preference test and serum level of CORT was determined by radioimmunoassay. Protein expression levels of hippocampal synaptophysin (SYP) and postsynaptic density-95(PSD-95) were detected by Western blot. Somal volume and protrusion length of glial fibrillary acidic protein-positive astrocytes were assayed by immunocytochemistry and quantitative stereological techniques. Results Immobility time in model group ((137.95±6.22)s) was significantly extended in comparison with that in the control group ((114.05±4.12)s)(P<0.01). Sucrose preference in the model group(62.42±6.75)% was lower than that in the control group (86.52±5.08)% (P<0.01) . CORT levels in model group ((11.48±0.62) ng/ml) was significantly increased compared with that in the control group ((1.11±0.05)ng/ml) (P<0.01). Hippocampal SYP (0.54±0.04) and PSD-95(0.57±0.07) expression levels in model group were lower than those in the control group (0.99±0.14), (1.03±0.10) (P<0.01). Somal volume in the model group ((132.04±9.23)μm3) and protrusion length ((1.39±0.05)×107μm) was lower than that in the control group ((168.49±9.01)μm3), (1.77±0.10)×107μm)(P<0.05, P<0.01). SYP and PSD-95 expression level was found to be positively correlated with the reduction of the protrusion length(r=0.660, P<0.01; r=0.614, P<0.01)in astrocytes. Conclusion The results suggest that depression-like behavior-induced by long-term CORT treatment is possibly caused by the alternation of the synaptic plasticity associated with the reduction of the reducing the protrusion length. Key words: Corticosterone; Astrocyte; Depression; Synapse