Effects of hippocampal PGC-1α on depression-like behaviors and number of astrocytes in hippocampal subregions in mice

Objective To investigate the effects of targeted silence/overexpression of PGC-1α in the hippocampus on depression-like behaviors in mice and on the number of glial fibrillary acidic protein positive (GFAP+) astrocytes in the subregions of the hippocampus. Methods After adaptive feeding and sucrose preference baseline adjustment, 32 male C57BL/6 mice aged 6~8 weeks were randomly divided into empty virus group (n=14), PGC-1α silencing group (n=11) and PGC-1α overexpression group (n=7). The latter 2 groups were injected with adeno-associated virus (AAV)-mediated genes silencing or overexpressing PGC-1α in the hippocampus, respectively, with aid of stereotactic injection technique. Sucrose preference test (SPT) and forced swimming test (FST) were performed to assess the depression-like behaviors, and the number of GFAP+ astrocytes in each hippocampal subregion was accurately quantified in 3 dimensions by immunohistochemistry and stereology. Results As compared with the empty virus group, the PGC-1α silencing group had significantly decreased percentage of sucrose preference (P < 0.01), prolonged immobility time in FST (P < 0.05), and larger number of GFAP+ astrocytes in both CA1 and DG subregions(P < 0.05). However, the immobility time in FST was remarkably shortened in the PGC-1α overexpression group (P < 0.01), with the number of GFAP+ astrocytes in CA1 and DG subregions diminished (P < 0.05). There was no significant difference in the percentage of sucrose preference between the empty virus group and PGC-1α overexpression group, and silencing or overexpressing PGC-1α showed no obvious impact on the number of astrocytes in CA3 subregion. Conclusion PGC-1α is closely associated with the depression-like behaviors and participates in regulating the number of GFAP+ astrocytes in CA1 and DG subregions in mice.