Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China; Department of Clinical Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China.
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China.
Behav Brain Res. 2019 Dec 30;376:112207. doi: 10.1016/j.bbr.2019.112207. Epub 2019 Aug 30.
Although the dorsal hippocampus (dHPC) and serotonin (5-HT) receptor are involved in cognition, their roles in cognitive impairments in Parkinson' disease (PD) are still unclear. In the present study, the effects of the 5-HT receptor agonist 8-OH-DPAT and antagonist WAY100635 administrated into the dHPC of rats were assessed in T-maze rewarded alternation test for working memory and in hole-board test for long-term habituation. Unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle in rats impaired working memory and long-term habituation, decreased dopamine (DA) levels in the medial prefrontal cortex (mPFC), dHPC and ventral hippocampus (vHPC), and decreased the mean density of 5-HT receptors and co-localization of 5-HT receptor and excitatory amino acid carrier 1-immunoreactive (EAAC1-ir) neurons in the dHPC compared to sham-operated rats. Activation of dHPC 5-HT receptors by local infusion of 8-OH-DPAT impaired working memory and long-term habituation in both sham-operated and the 6-OHDA-lesioned rats. Furthermore, blockade of dHPC 5-HT receptors by WAY100635 improved the memories in the 6-OHDA-lesioned rats, but had no effects in sham-operated rats. Additionally, dHPC injection of 8-OH-DPAT decreased noradrenaline (NA) levels, increased 5-HT levels in the mPFC, dHPC and vHPC in sham-operated and lesioned rats, while WAY100635 increased DA and NA levels only in lesioned rats. The results of the present study suggest that dHPC 5-HT receptors regulate cognitive impairments in PD by changes of monoamines in the related brain regions.
尽管背侧海马体（dHPC）和 5-羟色胺（5-HT）受体与认知有关，但它们在帕金森病（PD）认知障碍中的作用仍不清楚。在本研究中，评估了 5-HT 受体激动剂 8-OH-DPAT 和拮抗剂 WAY100635 给药于大鼠 dHPC 对 T 迷宫奖励交替测试（用于工作记忆）和洞板测试（用于长期习惯化）的影响。大鼠内侧前脑束单侧 6-羟多巴胺（6-OHDA）损伤损害了工作记忆和长期习惯化，降低了内侧前额叶皮层（mPFC）、dHPC 和腹侧海马体（vHPC）中的多巴胺（DA）水平，降低了 dHPC 中 5-HT 受体的平均密度和 5-HT 受体与兴奋性氨基酸载体 1-免疫反应（EAAC1-ir）神经元的共定位。与假手术大鼠相比，dHPC 5-HT 受体的激活通过局部输注 8-OH-DPAT 损害了假手术和 6-OHDA 损伤大鼠的工作记忆和长期习惯化。此外，dHPC 5-HT 受体阻断剂 WAY100635 改善了 6-OHDA 损伤大鼠的记忆，但对假手术大鼠没有影响。此外，dHPC 注射 8-OH-DPAT 降低了假手术和损伤大鼠的 mPFC、dHPC 和 vHPC 中的去甲肾上腺素（NA）水平，增加了 5-HT 水平，而 WAY100635 仅增加了损伤大鼠的 DA 和 NA 水平。本研究的结果表明，dHPC 5-HT 受体通过改变相关脑区的单胺类物质来调节 PD 中的认知障碍。
