TGF-β1 Protects Trauma-injured Murine Cortical Neurons by Upregulating L-type Calcium Channel Cav1.2 via the p38 Pathway

  • Neuroscience. 2022 Jun 1;492:47-57. doi: 10.1016/j.neuroscience.2022.04.010.
Yanlei Li  1 ,  Weiqiang Chen  2 ,  Huixiong Deng  3 ,  Tian Li  4 ,  Zhenning Liu  5 ,  Xueer Liu  6 ,  Zelin Zhang  7 ,  Xiaoxuan Chen  8 ,  Jiangtao Sheng  9 ,  Kangsheng Li  10
Affiliations
  • 1. Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: [email protected].
  • 2. Department of Neurosurgery, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China. Electronic address: [email protected].
  • 3. Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: [email protected].
  • 4. Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: [email protected].
  • 5. Department of Laboratory, Guangzhou Chest Hospital, China. Electronic address: [email protected].
  • 6. Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: [email protected].
  • 7. Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: [email protected].
  • 8. Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: [email protected].
  • 9. Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: [email protected].
  • 10. Department of Microbiology and Immunology, Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, China. Electronic address: [email protected].
PMID: 35460836 DOI: 10.1016/j.neuroscience.2022.04.010
Abstract

Traumatic brain injury (TBI) is a leading cause of disability and death in adolescents, and there is a lack of effective methods of treatment. The neuroprotective effects exerted by TGF-β1 can ameliorate a range of neuronal lesions in multiple central nervous system diseases. In this study, we used an in-vitro TBI model of mechanical injury on murine primary cortical neurons and the neuro-2a cell line to investigate the neuroprotective role played by TGF-β1 in cortical neurons in TBI. Our results showed that TGF-β1 significantly increased neuronal viability and inhibited Apoptosis for 24 h after trauma. The expression of CAv1.2, an L-type calcium channel (LTCC) isoform, decreased significantly after trauma injury, and this change was reversed by TGF-β1. Nimodipine, a classic LTCC blocker, abolished the protective effect of TGF-β1 on trauma-induced neuronal Apoptosis. The knockdown of CAv1.2 in differentiated neuro-2a cells significantly inhibited the anti-apoptosis effect of TGF-β1 exerted on injured neuro-2a cells. Moreover, TGF-β1 rescued and enhanced the trauma-suppressed neuro-2a intracellular CA2+ concentration, while the effect of TGF-β1 was partially inhibited by nimodipine. TGF-β1 significantly upregulated the expression of CAv1.2 by activating the p38 MAPK pathway and by inhibiting trauma-induced neuronal Apoptosis. In conclusion, TGF-β1 increased trauma-injured murine cortical neuronal activity and inhibited Apoptosis by upregulating Cav1.2 channels via activating the p38 MAPK pathway. Therefore, the TGF-β1/p38 MAPK/CAv 1.2 pathway has the potential to be used as a novel therapeutic target for TBI.

Keywords
L-type calcium channel; cortical neuron; neuro-2a; p38-mitogen-activated protein kinase; transforming growth factor-β1; traumatic brain injury.
Products