Biomedical Research Foundation, Hospital Clínico San Calos-IdISSC, 28040 Madrid, Spain.
Department of Pharmacology, University of the Basque Country, UPV/EHU, 48940 Leioa, Spain.
Int J Mol Sci. 2023 Feb 6;24(4):3229. doi: 10.3390/ijms24043229.
Post-stroke mood disorders (PSMD) affect disease prognosis in adults. Adult rodent models underlie the importance of the dopamine (DA) system in PSMD pathophysiology. There are no studies on PSMD after neonatal stroke. We induced neonatal stroke in 7-day-old (P7) rats by temporal left middle cerebral artery occlusion (MCAO). Performance in the tail suspension test (TST) at P14 and the forced swimming test (FST) and open field test (OFT) at P37 were studied to assess PSMD. DA neuron density in the ventral tegmental area, brain DA concentration and DA transporter (DAT) expression as well as D2 receptor (D2R) expression and G-protein functional coupling were also studied. MCAO animals revealed depressive-like symptoms at P14 associated with decreased DA concentration and reduced DA neuron population and DAT expression. At P37, MCAO rats showed hyperactive behavior associated with increased DA concentration, normalization of DA neuron density and decreased DAT expression. MCAO did not modify D2R expression but reduced D2R functionality at P37. MCAO-induced depressive-like symptoms were reversed by the DA reuptake inhibitor GBR-12909. In conclusion, MCAO in newborn rats induced depressive-like symptoms and hyperactive behavior in the medium and long term, respectively, that were associated with alterations in the DA system.
卒中后情绪障碍（PSMD）会影响成年人的疾病预后。成年啮齿动物模型是多巴胺（DA）系统在 PSMD 病理生理学中的重要性的基础。目前尚无关于新生儿卒中后 PSMD 的研究。我们通过颞叶左大脑中动脉闭塞（MCAO）在 7 天大（P7）的大鼠中诱导新生儿卒中。在 P14 进行悬尾试验（TST），在 P37 进行强迫游泳试验（FST）和旷场试验（OFT），以评估 PSMD。还研究了腹侧被盖区的 DA 神经元密度、脑 DA 浓度和 DA 转运体（DAT）表达以及 D2 受体（D2R）表达和 G 蛋白功能偶联。MCAO 动物在 P14 时表现出抑郁样症状，与 DA 浓度降低和 DA 神经元群体减少以及 DAT 表达降低有关。在 P37 时，MCAO 大鼠表现出多动行为，与 DA 浓度增加、DA 神经元密度正常化和 DAT 表达减少有关。MCAO 没有改变 D2R 表达，但在 P37 时降低了 D2R 功能。DA 再摄取抑制剂 GBR-12909 逆转了 MCAO 诱导的抑郁样症状。总之，新生大鼠 MCAO 分别在中期和长期诱导抑郁样症状和多动行为，与 DA 系统的改变有关。
