Sensing of extracellular matrix in motor circuit remodelling: a novel target for neuroplasticity-promoting stroke therapies?

运动回路重塑中细胞外基质的感知：促进神经可塑性的中风治疗的新靶点？

• 批准号: 467228103
• 负责人: Egor Dzyubenko, Ph.D.
• 金额: --
• 依托单位: Klinik für Neurologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/467228103?language=en
• 关键词: Sensing; extracellular; matrix; motor; circuit

This project postulates that extracellular matrix (ECM) degradation re-opens a neuroplasticity window following ischemic stroke that contributes to motor-coordination recovery. As an underlying mechanism, we will characterize the role of mechanoreceptors in controlling astrocytic and neuronal network remodeling. We hypothesize that the downregulation of mechanotransduction represents a key mechanism via which post-ischemic ECM degradation reduces calcium oscillations and functional coupling in astrocytes. The reduction of astrocytic network activity will deregulate neurotransmission, at the same time facilitating the release of synaptic guidance molecules. Accordingly, the activity of neuronal networks will be enhanced, and the establishment of new synapses will be enabled. With the experiments planned, we hope to establish the brain’s ECM as novel target for plasticity-promoting stroke therapies.

该项目假设细胞外基质（ECM）降解在缺血性中风后重新打开神经可塑性窗口，有助于运动协调恢复。作为潜在的机制，我们将描述机械受体在控制星形细胞和神经元网络重塑中的作用。我们假设机械转导的下调是缺血后ECM降解减少星形胶质细胞钙振荡和功能偶联的关键机制。星形胶质细胞网络活动的减少将解除对神经传递的调节，同时促进突触引导分子的释放。因此，神经网络的活动将增强，新的突触的建立将成为可能。随着实验计划的进行，我们希望将大脑的ECM作为促进可塑性的中风治疗的新靶点。