Effects of wheel-running on anxiety and depression-relevant behaviours in the MCAO mouse model of stroke: moderation of brain-derived neurotrophic factor and serotonin receptor gene expression
Effects of wheel-running on anxiety and depression-relevant behaviours in the MCAO mouse model of stroke: moderation of brain-derived neurotrophic factor and serotonin receptor gene expression
复制标题
DOI：
10.1016/j.bbr.2022.113983
复制
发表时间：
2022-07-01
影响因子：
2.7
通讯作者：
Pang, Terence Y.
中科院分区：
文献类型：
--
作者：
Brait, Vanessa H.;Jackman, Katherine A.;Pang, Terence Y.
中风仍然是全球死亡的主要原因。中风后的治疗因病理的异质性而复杂化，继发性心理症状的出现是恢复过程的额外挑战。卒中后抑郁症（PSD）是一种常见的合并症，是恢复的主要障碍。虽然选择性5-羟色胺再摄取抑制剂（SSRIs）已被证明是临床有效的治疗PSD，发病过程中表现出的抑郁情绪中风后仍不清楚。此外，SSRIs的使用与脑出血的风险相关，因此需要不断探索替代治疗方案。运动已被证明有利于改善人类和神经系统疾病的临床前模型的情绪。很少有人知道中风后体育锻炼的情绪相关的好处。使用大脑中动脉闭塞（MCAO）小鼠模型的脑缺血，我们调查是否行为缺陷出现后MCAO，可以通过自愿轮运行。我们报告说，MCAO诱导hypo-motion和快感缺乏相关的行为，与轮运行赋予的一些改善。5-羟色胺转运体基因表达在大脑中动脉闭塞的海马和额叶皮层增加，但这种增加仍然存在，尽管车轮运行。在MCAO小鼠中，与车轮运行相关的BDNF基因表达上调不受影响，反映了关键神经可塑性分子途径的保守性。总之，我们的研究结果强调了进一步研究脑卒中情感症状的多巴胺能调节的必要性。
Stroke continues to be a major cause of mortality globally. Post-stroke treatment is complicated by the heterogenous nature of pathology and the emergence of secondary psychological symptoms are an additional challenge to the recovery process. Poststroke depression (PSD) is a common co-morbidity and is a major impediment to recovery. While selective serotonin reuptake inhibitors (SSRIs) have proven to be clinically efficacious in treating PSD, the pathogenic processes that underlie the manifestation of depressive mood post-stroke remains unclear. Furthermore, the use of SSRIs is associated with risks of intracerebral haemorrhage, so alternative treatment options need to be continuously explored. Exercise has been demonstrated to be beneficial for improving mood in humans and preclinical models of neurological conditions. Little is known of the mood related benefits of physical exercise post-stroke. Using the middle cerebral artery occlusion (MCAO) mouse model of cerebral ischaemia, we investigated whether behavioural deficits emerge post-MCAO and could be rescued by voluntary wheel-running. We report that MCAO induced hypo-locomotion and anhedonia-related behaviours, with some improvements conferred by wheel-running. Serotonin transporter gene expression was increased in the MCAO hippocampus and frontal cortex, but this increase remained despite wheel-running. Wheel-running associated up-regulation of BDNF gene expression was unaffected in MCAO mice, reflecting conservation of key neuroplasticity molecular pathways. Taken together, our results highlight the need for further research into serotonergic modulation of the affective symptoms of stroke.