Abstract:
Glymphatic system denotes a brain-wide pathway that eliminates extracellular solutes from brain. It is driven by the flow of brain interstitial fluid (ISF) and cerebrospinal fluid (CSF) via perivascular spaces. Glymphatic convective flow is driven by cerebral arterial pulsation, which is facilitated by a water channel, aquaporin-4 (AQP4) expressed in astrocytic end-foot processes. Since its discovery, the glymphatic system receives a considerable scientific attention due to its pivotal role in clearing metabolic waste as well as neurotoxic substances such as amyloid b peptide. Tau is a microtubule binding protein, however it is also physiologically released into extracellular fluids. The presence of tau in the blood stream indicates that it is eventually cleared from the brain to the periphery, however, the detailed mechanisms that eliminate extracellular tau from the central nervous system remained to be elucidated. Recently, we and others have reported that extracellular tau is eliminated from the brain to CSF by an AQP4 dependent mechanism, suggesting the involvement of the glymphatic system. In this chapter, we describe the detailed protocol of how we can assess glymphatic outflow of tau protein from brain to CSF in mice.
摘要:
淋巴系统表示从脑中消除细胞外溶质的全脑途径。它是由脑间质液(ISF)和脑脊液(CSF)通过血管周围间隙的流动驱动的。淋巴对流是由脑动脉搏动驱动的,这是由水道促进的,水通道蛋白4(AQP4)在星形细胞末端足突中表达。自从它被发现,由于其在清除代谢废物以及神经毒性物质如淀粉样蛋白b肽方面的关键作用,淋巴系统受到了相当大的科学关注。Tau是一种微管结合蛋白,然而,它也在生理上释放到细胞外液中。tau在血流中的存在表明它最终从大脑清除到外围,然而,从中枢神经系统中消除细胞外tau的详细机制仍有待阐明。最近,我们和其他人已经报道,通过AQP4依赖性机制,细胞外tau从脑到CSF被消除,提示淋巴系统的参与。在这一章中,我们描述了如何评估小鼠中从脑到CSF的tau蛋白的淋巴淋巴流出的详细方案。