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TGF-β1 Protects Trauma-injured Murine Cortical Neurons by Upregulating L-type Calcium Channel Ca v 1.2 via the p38 Pathway.
- Source :
-
Neuroscience [Neuroscience] 2022 Jun 01; Vol. 492, pp. 47-57. Date of Electronic Publication: 2022 Apr 20. - Publication Year :
- 2022
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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 Ca <subscript>v</subscript> 1.2, 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 Ca <subscript>v</subscript> 1.2 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 Ca <superscript>2+</superscript> concentration, while the effect of TGF-β1 was partially inhibited by nimodipine. TGF-β1 significantly upregulated the expression of Ca <subscript>v</subscript> 1.2 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/Ca <subscript>v</subscript> 1.2 pathway has the potential to be used as a novel therapeutic target for TBI.<br /> (Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Cells, Cultured
Mice
Neurons metabolism
Nimodipine pharmacology
Transforming Growth Factor beta metabolism
p38 Mitogen-Activated Protein Kinases metabolism
Calcium Channels, L-Type metabolism
Transforming Growth Factor beta1 metabolism
Transforming Growth Factor beta1 pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7544
- Volume :
- 492
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 35460836
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2022.04.010