Positive effects of running exercise on astrocytes in the medial prefrontal cortex in an animal model of depression
Positive effects of running exercise on astrocytes in the medial prefrontal cortex in an animal model of depression
复制标题
跑步运动对抑郁动物模型内侧前额皮质星形胶质细胞的积极影响
DOI：
10.1002/cne.25397
复制
发表时间：
2022-08-16
影响因子：
2.5
通讯作者：
Tang, Yong
中科院分区：
文献类型：
--
作者：
Huang, Dujuan;Xiao, Qian;Tang, Yong
抑郁症是最常见的精神疾病之一，严重影响生活的各个方面。跑步运动被认为可以预防或缓解抑郁症的发生和发展，但其作用机制尚不清楚。独立的研究表明，星形胶质细胞发挥重要作用，内侧前额叶皮层（mPFC）是一个重要的大脑区域参与病理基础抑郁症。然而，目前尚不清楚跑步运动是否通过影响mPFC中星形胶质细胞的数量和谷氨酸转运功能来达到抗抑郁作用。在这里，抑郁症的动物模型，建立了慢性不可预测的压力（CUS），抑郁样行为进行了评估的蔗糖偏好测试。成功建立抑郁模型后，实验动物进行跑步运动。采用免疫组化和体视学方法精确定量mPFC中胶质细胞酸性蛋白阳性（GFAP（+））细胞数，并采用半定量免疫荧光法测量mPFC中溴脱氧尿苷阳性（BrdU（+））和BrdU（+）/GFAP（+）细胞密度。通过mRNA测序和qRT-PCR检测mPFC星形胶质细胞中谷氨酸转运体基因表达的变化。我们发现，跑步运动逆转了CUS动物mPFC中GFAP，S100 b和谷氨酸转运蛋白GLT-1和GLAST基因表达水平的降低，增加了星形胶质细胞的数量和新生星形胶质细胞的密度。这些结果表明，星形胶质细胞数量和谷氨酸转运体功能的变化可能是跑步运动治疗抑郁症的潜在调节因素。
Depression is one of the most common mental illnesses and seriously affects all aspects of life. Running exercise has been suggested to prevent or alleviate the occurrence and development of depression; however, the underlying mechanisms of these effects remain unclear. Independent studies have indicated that astrocytes play essential roles and that the medial prefrontal cortex (mPFC) is an important brain region involved in the pathology underlying depression. However, it is unknown whether running exercise achieves antidepressant effects by affecting the number of astrocytes and glutamate transport function in the mPFC. Here, animal models of depression were established using chronic unpredictable stress (CUS), and depression-like behavior was assessed by the sucrose preference test. After successfully establishing the depression model, experimental animals performed running exercise. Glial fibrillary acidic protein-positive (GFAP(+)) cell number in the mPFC was precisely quantified using immunohistochemical and stereological methods, and the densities of bromodeoxyuridine-positive (BrdU(+)) and BrdU(+)/GFAP(+) cells in the mPFC were measured using a semiquantitative immunofluorescence assay. Changes in glutamate transporter gene expression in mPFC astrocytes were detected by mRNA sequencing and qRT-PCR. We found that running exercise reversed CUS-induced decreases in sucrose preference, increased astrocyte number and the density of newborn astrocytes, and reversed decreases in gene expression levels of GFAP, S100b, and the glutamate transporters GLT-1 and GLAST in the mPFC of CUS animals. These results suggested that changes in astrocyte number and glutamate transporter function may be potential meditators of the effects of running exercise in the treatment of depression.