Dataset Information

Fascin-1 limits myosin activity in microglia to control mechanical characterization of the injured spinal cord.

ABSTRACT:

Background

Mechanical softening of the glial scar region regulates axonal regeneration to impede neurological recovery in central nervous system (CNS) injury. Microglia, a crucial cellular component of the glial scar, facilitate neuronal survival and neurological recovery after spinal cord injury (SCI). However, the critical mechanical characterization of injured spinal cord that harmonizes neuroprotective function of microglia remains poorly understood.

Methods

Spinal cord tissue stiffness was assessed using atomic force microscopy (AFM) in a mouse model of crush injury. Pharmacological depletion of microglia using PLX5622 was used to explore the effect of microglia on mechanical characterization. Conditional knockout of Fascin-1 in microglia (Fascin-1 CKO) alone or in combination with inhibition of myosin activity was performed to delve into relevant mechanisms of microglia regulating mechanical signal. Immunofluorescence staining was performed to evaluate the related protein levels, inflammatory cells, and neuron survival after SCI. The Basso mouse scale score was calculated to assess functional recovery.

Results

Spinal cord tissue significantly softens after SCI. Microglia depletion or Fascin-1 knockout in microglia limits tissue softening and alters mechanical characterization, which leads to increased tissue pathology and impaired functional recovery. Mechanistically, Fascin-1 inhibits myosin activation to promote microglial migration and control mechanical characterization after SCI.

Conclusions

We reveal that Fascin-1 limits myosin activity to regulate mechanical characterization after SCI, and this mechanical signal should be considered in future approaches for the treatment of CNS diseases.

SUBMITTER: Huang J

PROVIDER: S-EPMC11005239 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Publications

Fascin-1 limits myosin activity in microglia to control mechanical characterization of the injured spinal cord.

Huang Jinxin J Hu Xuyang X Chen Zeqiang Z Ouyang Fangru F Li Jianjian J Hu Yixue Y Zhao Yuanzhe Y Wang Jingwen J Yao Fei F Jing Juehua J Cheng Li L

Journal of neuroinflammation 20240410 1

<h4>Background</h4>Mechanical softening of the glial scar region regulates axonal regeneration to impede neurological recovery in central nervous system (CNS) injury. Microglia, a crucial cellular component of the glial scar, facilitate neuronal survival and neurological recovery after spinal cord injury (SCI). However, the critical mechanical characterization of injured spinal cord that harmonizes neuroprotective function of microglia remains poorly understood.<h4>Methods</h4>Spinal cord tissue ...[more]

PMID: 38600569

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Dataset Information

Fascin-1 limits myosin activity in microglia to control mechanical characterization of the injured spinal cord.

Background

Methods

Results

Conclusions

Publications

Fascin-1 limits myosin activity in microglia to control mechanical characterization of the injured spinal cord.

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