miR-132调控额叶-皮层下神经环路改善卒中后痴呆的机制研究

Synaptic plasticity in frontal-subcortical circuits is closely related to the pathogenesis of post-stroke dementia (PSD). Preliminary studies demonstrated that miR-132 levels in frontal-subcortical circuits of PSD mice were markly lower than that of normal group. which impaired synaptic morphology, decreased synaptic mass, reduced synaptophysin expression. And miR-132 can attenuate these pathological changes. Similar results were obtained in the primary cortical neurons of OGD-mice, These observations suggest that miR-132 can regulate the synaptic plasticity in frontal-subcortical circuits of PSD mice. This study will mainly focus on the following two parts: 1) to confirm that miR-132 is able to modify synaptic plasticity in frontal-subcortical circuits of PSD mice; 2) to investigate whether miR - 132 exerts its effects through downregulation of SLC6A1 or VAPA gene. This project firstly proposed that miR-132 is involved in the pathogenesis of PSD by regluting synaptic plasticity in the frontal-subcortical circuits. Futhermore, the molecular mechanism underlying it is inhibiting the expression of the SLC6A1 or VAPA gene. This study will provide new targets and strategies for early diagnosis and treatment for PSD.

额叶-皮层下神经环路可塑性与卒中后痴呆（PSD）密切相关。前期研究发现，PSD小鼠额叶-皮层下神经环路中miR-132表达明显降低，突触形态受损，数量减少，突触素蛋白表达减少，而miR-132可改善此病理变化；在OGD小鼠原代皮层神经元中，miR-132亦明显改善OGD损伤的神经突触数和结构。提示miR-132可以调控PSD额叶-皮层下神经环路可塑性。本课题利用行为学、病理学、分子生物学等技术进行以下体内外研究：1）明确miR-132调控PSD相关的额叶-皮层下神经环路可塑性；2）探讨miR-132是否通过下调SLC6A1或VAPA基因发挥其调控神经环路可塑性的机制。本项目首次提出了miR-132调控额叶-皮层下环路突触可塑性参与了PSD的发病机制，并提出其可能机制，即通过抑制SLC6A1或VAPA蛋白表达，调控额叶-皮层下神经环路可塑性。为PSD的早期诊断和治疗提供新的理念和策略。