海马PGC-1α对小鼠抑郁样行为及海马各亚区星形胶质细胞数量的影响

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

目的探讨定向沉默/过表达小鼠海马中过氧化物酶体增殖物激活受体γ辅激活因子1α(PPAR gamma coactivator 1 alpha,PGC-1α)对小鼠抑郁样行为和海马各亚区胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)阳性(+)星形胶质细胞数量的影响。方法选取32只6~8周龄的雄性C57BL/6小鼠,在经过适应性喂养和糖水偏好基线调整后按照简单随机抽样方法分为空病毒组(n=14)、PGC-1α沉默组(n=11)和PGC-1α过表达组(n=7),分别采用海马立体定位注射技术以腺相关病毒为载体定向沉默/过表达小鼠海马中PGC-1α基因。运用糖水偏好实验和强迫游泳实验评估小鼠的抑郁样行为,采用免疫组织化学和现代体视学相结合的方法对小鼠海马各亚区中GFAP^(+)星形胶质细胞数量进行精确三维定量研究。结果与空病毒组小鼠相比,PGC-1α沉默组小鼠的糖水偏好百分比显著降低(P<0.01),强迫游泳实验不动时间显著增加(P<0.05),海马CA1和DG区中的GFAP^(+)星形胶质细胞数量显著增加(P<0.05);而PGC-1α过表达组小鼠的强迫游泳实验不动时间显著减少(P<0.01),海马CA1和DG区中的GFAP^(+)星形胶质细胞数量显著减少(P<0.05)。空病毒组与PGC-1α过表达组小鼠的糖水偏好百分比差异无统计学意义。沉默/过表达海马PGC-1α对CA3区星形胶质细胞数量的影响差异无统计学意义。结论小鼠海马PGC-1α与抑郁样行为密切相关,并参与海马CA1和DG区内GFAP^(+)星形胶质细胞数量的调节。

Objective To investigate the effects of targeted silence/overexpression of PGC-1αin 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 C57 BL/6 mice aged 6~8 weeks were randomly divided into empty virus group(n=14),PGC-1αsilencing group(n=11)and PGC-1αoverexpression group(n=7).The latter 2 groups were injected with adeno-associated virus(AAV)-mediated genes silencing or overexpressing PGC-1αin 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-1αsilencing 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-1αoverexpression 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-1αoverexpression group,and silencing or overexpressing PGC-1αshowed no obvious impact on the number of astrocytes in CA3 subregion.Conclusion PGC-1αis closely associated with the depression-like behaviors and participates in regulating the number of GFAP^(+)astrocytes in CA1 and DG subregions in mice.