Fluoxetine adjunct to therapeutic exercise promotes motor recovery in rats with cerebral ischemia: Roles of nucleus accumbens
Fluoxetine adjunct to therapeutic exercise promotes motor recovery in rats with cerebral ischemia: Roles of nucleus accumbens
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氟西汀辅助治疗性运动促进脑缺血大鼠的运动恢复：伏隔核的作用
DOI：
10.1016/j.brainresbull.2019.07.022
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发表时间：
2019-11-01
影响因子：
3.8
通讯作者：
Bai, Yu-Long
中科院分区：
文献类型：
--
作者：
Hua, Yan;Li, Ce;Bai, Yu-Long
本研究采用大鼠大脑中动脉闭塞（MCAO）脑缺血模型，探讨氟西汀辅助运动治疗促进运动恢复的分子机制。我们推测，延髓核（NAc）可能是氟西汀的反应区域之一，其中5-羟色胺（5-HT）和Delta FosB的相关升高与运动行为恢复相关。将雄性Sprague-Dawley大鼠随机分为5组：未进行干预的大鼠;未进行运动或氟西汀的MCAO大鼠;仅用氟西汀治疗的MCAO大鼠;仅用运动治疗的MCAO大鼠;以及运动和氟西汀治疗的MCAO大鼠。运动功能和动机通过错误脚步试验和强迫游泳试验进行评估。检测双侧NAc内5-HT水平及同侧NAc内5-HT 2C受体（5-HT 2CR）和Delta FosB的表达。相关性采用Pearson相关分析。我们的研究结果表明，无论是治疗有助于改善患肢的抓握灵巧性，运动动机，和对不利环境的恢复力在MCAO大鼠。氟西汀和运动的双重治疗可能会加速康复过程。双重治疗通过显著增加同侧NAc的5-HT水平，帮助恢复双侧NAc之间的平衡。两种治疗方法均可使患侧NAc 5-HT 2CR表达恢复至接近正常水平，并与运动功能恢复相关。双重治疗显著增加了同侧NAc中Delta FosB的表达，这与双侧NAc中5-HT的平衡有关，但与运动恢复无直接关系。因此，NAc可能在脑卒中后运动动机的驱动中发挥重要作用，这可能与脑卒中后运动恢复有关。氟西汀可能通过调节NAc中5-HT及其受体而促进治疗性运动的效果。
The study aimed to explore the molecular mechanism of fluoxetine as an adjunct to therapeutic exercise to improve motor recovery using a rat cerebral ischemic model with middle cerebral artery occlusion (MCAO). We hypothesized that the nucleus accumbens (NAc) may be one of the responding areas to fluoxetine where relevant elevations in 5-hydroxytryptamine (5-HT) and Delta FosB were associated with motor behavioral recovery. Male Sprague-Dawley rats were randomly divided into five groups: rats without intervention; rats that underwent MCAO without exercise or fluoxetine; rats that underwent MCAO treated only with fluoxetine; rats that underwent MCAO treated only with exercise; and rats that underwent MCAO treated with both exercise and fluoxetine. Motor function and motivation were assessed by the fault footsteps test and the forced swimming test. 5-HT level in the bilateral NAc and the expression of 5-HT2C receptor (5-HT2CR) and Delta FosB in the ipsilesional (left) NAc were measured. Correlation was explored by Pearson correlation analysis. Our results indicated that either treatment helped improve the grasp dexterity of the affected limb, motor motivation, and resilience to adverse environment in MCAO rats. The dual treatment with fluoxetine and exercise may hasten the recovery process. The dual treatment helped restore the balance of 5-HT level between the bilateral NAc by significantly increasing its level in the ipsilesional side. Either treatment could resume the expression of 5-HT2CR in the ipsilesional side of the NAc close to the normal level, which was correlated with motor recovery. The dual treatment significantly increased the expression of Delta FosB in the ipsilesional side of the NAc, which was correlated with the balance of 5-HT in the bilateral NAc, but not directly with motor recovery. In conclusion, the NAc may play an important role in driving physical motivation, which was possibly related to motor recovery after stroke. Fluoxetine may hasten the effectiveness of therapeutic exercise, possibly via regulating 5-HT and its receptors in the NAc.