基于脑血管Semaphorin3G信号紊乱的血管性痴呆发病机制及调控研究

The underlying molecular mechanisms of vascular dementia remain to be fully understood. In our recent study, the dramatic decline of Semaphorin3G was observed in the cerebral microvessel of vascular dementia mice model. Consistently, the cognitive deficits were observed in the Semaphorin3G conditional knockout mice (Cdh5-Cre;Sema3Gf/f). The study of the molecular mechanism behind these phenomena will be very significant for the analysis and treatment of vascular dementia. Therefore, the present study designed to address the precise role of neurovascular Semaphorin3G signaling during pathological progression of vascular dementia. Firstly, we will examine the spatiotemporal changes of Semaphorin3G signaling in the pathological process of vascular dementia. Secondly, by using pharmacological and molecular methods, we further investigate the interrelationship between the Semaphorin3G signaling and injury of hippocampal neuronal circuit during vascular dementia. Thirdly, we examine whether targeting Semaphorin3G signaling could contribute to preservation or restoration of pathological damage during vascular dementia. The precise understanding of Semaphorin3G signaling might lead to novel therapeutic strategies to ameliorate cognitive deficits in vascular dementia.

血管性痴呆发病机理仍不清，深入解析其分子机制对寻找潜在药物靶标至关重要。我们前期发现血管性痴呆小鼠伴有脑血管Semaphorin3G （Sema3G）表达明显下降，而我们成功构建的脑血管内皮细胞Sema3G条件敲除小鼠也有认知功能障碍的表型。对于上述现象背后分子机制的研究将对进一步解析血管性痴呆有实际意义。因此，在以往研究基础上，本项目以脑血管Sema3G作为切入点开展深入探索：①脑血管Sema3G在血管性痴呆病理过程中的时空动态变化规律如何？② 阐明血管性痴呆病理过程中脑血管Sema3G信号变化与海马神经元功能障碍的内在关联性；③探究脑血管Sema3G信号调控策略对改善血管性痴呆病理损害的作用。本课题的开展将揭示血管性痴呆病理过程中基于Sema3G信号的内皮细胞与海马神经元间信号通讯模式及规律，为理解血管性痴呆发病机理及制定防治策略提供新的视角和分子靶标。

血管性痴呆发病机理仍不清，深入解析其分子机制对寻找潜在药物靶标至关重要。我们前期发现血管性痴呆小鼠伴有脑血管Semaphorin3G （Sema3G）表达明显下降，而我们成功构建的脑血管内皮细胞Sema3G条件敲除小鼠也有认知功能障碍的表型。对于上述现象背后分子机制的研究将对进一步解析血管性痴呆有实际意义。因此，在以往研究基础上，本项目以脑血管Sema3G作为切入点开展深入探索：①脑血管Sema3G在血管性痴呆病理过程中的时空动态变化规律如何？② 阐明血管性痴呆病理过程中脑血管Sema3G信号变化与海马神经元功能障碍的内在关联性；③探究脑血管Sema3G信号调控策略对改善血管性痴呆病理损害的作用。本课题的开展将揭示血管性痴呆病理过程中基于Sema3G信号的内皮细胞与海马神经元间信号通讯模式及规律，为理解血管性痴呆发病机理及制定防治策略提供新的视角和分子靶标。