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

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

  • J Neuroinflammation. 2024 Apr 10;21(1):88. doi: 10.1186/s12974-024-03089-5.
Jinxin Huang # 1 2,  Xuyang Hu # 1 2,  Zeqiang Chen 1 2,  Fangru Ouyang 1 2,  Jianjian Li 1 2,  Yixue Hu 1 2,  Yuanzhe Zhao 1 2,  Jingwen Wang 1 2,  Fei Yao 3 4,  Juehua Jing 5 6,  Li Cheng 7 8
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
  • 2 Institute of Orthopaedics, Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
  • 3 Department of Orthopaedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China. feiyao@ustc.edu.cn.
  • 4 Institute of Orthopaedics, Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China. feiyao@ustc.edu.cn.
  • 5 Department of Orthopaedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China. jjhhu@sina.com.
  • 6 Institute of Orthopaedics, Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China. jjhhu@sina.com.
  • 7 Department of Orthopaedics, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China. chengli7788@163.com.
  • 8 Institute of Orthopaedics, Research Center for Translational Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China. chengli7788@163.com.
  • # Contributed equally.
PMID: 38600569 DOI: 10.1186/s12974-024-03089-5
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.

Keywords

Fascin-1; Mechanical characterization; Microglia; Myosin; Spinal cord injury.

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