多巴胺D3受体对卵巢激素相关学习记忆改变的调节机制研究

Ovarian hormones improve learning and memory through signal transduction pathways and bioenergetic systems. Although dopamine D3 receptor (D3R) is not critical to learning and memory, blocked D3R can improve aging or drug-induced memory impairment. However, the effect of D3R on ovarian hormones-related memory changes is unclear so far. Our previous study showed that D3R knockout ameliorate the ovarian hormones deprivation induced spatial working memory decline. Based on the literature and previous work, we hypothesize that D3R plays a role in homeostasis, and D3R may regulate learning and memory in pathological states including ovarian hormone deprivation. We select D3R knockout and wild-type mice as the subjects in our study, and reveal the mechanism behind learning and memory changes. Our project aim to clarify the intrinsic mechanism of the regulation of ovarian hormones-related learning and memory changes by D3R, and to understand the protection of D3R in homeostasis, and to provide a theoretical basis for experimental drug treatment of cognitive disorder.

卵巢激素具有保护神经、改善学习记忆的作用，可通过影响机体信号转导途径以及改变生物能耗平衡发挥效应。目前研究认为多巴胺D3受体（D3R）并非影响学习记忆的关键，但阻断D3R可缓解老龄化或药物诱导的记忆损害，然而D3R调节卵巢激素对学习记忆的作用机制迄今尚不清楚。我们前期发现D3R敲除可改善小鼠卵巢激素剥夺相关空间工作记忆减退，基于文献报道及前期工作，我们推测：D3R具维持机体稳态平衡的作用，对学习记忆的调控可能仅存在于病理状态，包括卵巢激素剥夺状态。本课题拟选择D3R敲除与野生型小鼠，对其进行手术及外源给药处理，分析学习记忆相关行为学改变，利用分子生物学、细胞生物学技术从信号转导通路层面与生物能耗平衡层面分析D3R对卵巢激素作用的调节机制。旨在阐明D3R调控卵巢激素相关学习记忆改变的内在机制，为深入理解D3R对机体稳态平衡的保护机制提供科学依据，并为认知障碍的药物治疗提供一定的实验理论基础。