Tsinghua University Reveals the Important Function of the Mechano-receptor Piezo1 in the Mechanosensing of the Central Nervous System

On August 12, 2022, the team of Xiao Bailong from the School of Pharmacy, Tsinghua University published a paper entitled "Piezo1 mediates astrocyte mechanotransduction and modulates adult hippocampal neurogenesis and cognition in the journal Neuro.

Research Background

The normal function and homeostasis of the brain depend on the effective transduction and synergy of various cells, including neurons, glial cells, and cerebral blood vessels, on various signals in the brain environmen.

Research result

To answer this scientific question, the researchers first used reporter mice fused to express Piezo1-tdTomato to identify the cell types in the brain that express the mechanically gated channel Piezo1. Interestingly, Piezo1 is widely expressed in astrocytes, in addition to Piezo1-expressing vascular endothelial cells, which have been previously identifie.

As the most abundant and widely distributed cell type in the mammalian brain, astrocytes have a typical multi-level branched structure, and the network formed by them can cover a very large tissue microenvironment (the volume of each astrocyte.

Using astrocyte-specific Piezo genetically modified mice, Piezo knockout astrocytes were isolated and cultured in vitro, and it was found that Piezo1 directly mediated the response of astrocytes to mechanical stimulation, induced cation current and cellular Influx of external Ca2.

In order to further reveal the role of astrocyte Piezo at the tissue cell level, the researchers used the adult neurogenesis microenvironment as an entry point to explore the effect of astrocyte Piezo knockout on the plasticity of hippocampal adult neurogenesi.

Using live brain slices to analyze long-term potentiation (LTP), the researchers found that LTP in the hippocampus of astrocyte Piezo knockout mice was significantly reduced compared to controls, while addition of ATP rescued LTP in Piezo knockout mic.

Through the behavioral analysis of astrocyte Piezo knockout mice at the overall level of animals, it was found that Piezo knockout mice showed decreased learning and memory functions in the water maze and Y maze test, indicating that astrocyte Piezo regulates the It plays an important role in the cognitive function of the brai.

Finally, using astrocyte Piezo1-overexpressing mice, the researchers confirmed that Piezo1 channels in astrocytes enhance synaptic plasticity and cognitive function by enhancing mechanical signal transduction, from both sufficiency and necessit.

The above research results have led researchers to think about how the Piezo channel located in the cell membrane senses the stimulation of the subtle mechanical forces in the brain? Xiao Bailong and Li Xueming's research group, through long-term collaborative research, recently answered this question by analyzing the dynamic structure of Piezo1 under stress on lipid membranes (Yang et a.

Figure 1 Changes in hippocampal volume of astrocyte Piezo knockout mic.

FigureA schematic diagram of astrocyte Piezo-mediated mechanical signal transduction in regulating brain structure and functio.

Significance

Taken together, this paper reveals that astrocytes efficiently regulate adult hippocampal neurogenesis and cognitive function using Piezo1 channel-mediated mechanotransduction mechanisms, conceptually emphasizing the importance of mechanotransduction in maintaining brain structure and functio.

Professor Xiao Bailong is the corresponding author of this paper, and D.

This work has been supported by the National Natural Science Foundation of China for Distinguished Young Scholars (31825014)/Key Projects (32130049)/Innovative Research Group Projects (32021002), and the National Ministry of Science and Technology 2030 Science and Technology Innovation - "Brain Science and Brain-like Research" Major Project (2021ZD0203301) ), the Tsinghua-Peking University Life Science Joint Center, the State Key Laboratory of Membrane Biology, the Tsinghua-IDG/McGovern Institute for Brain Science, the Beijing Frontier Research Center for Biological Structure, and the Advanced Innovation Center for Structural Biolog.