P2Y12 receptor mediates apoptosis and demyelination to affect functional recovery in mice with spinal cord injury.
Neurochem Int
; 171: 105641, 2023 Dec.
Article
en En
| MEDLINE
| ID: mdl-37952830
Among diseases of the central nervous system (CNS), spinal cord injury (SCI) has a high fatality rate. It has been proven that P2Y G protein-coupled purinergic receptors have a neuroprotective role in apoptosis and regeneration inside the damaged spinal cord. The P2Y12 receptor (P2Y12R) has recently been linked to peripheral neuropathy and stroke. However, the role of P2Y12R after SCI remains unclear. Our study randomly divided C57BL/6J female mice into 3 groups: Sham+DMSO, SCI+DMSO, and SCI+MRS2395. MRS2395 as a P2Y12R inhibitor was intraperitoneally injected at a dose of 1.5 mg/kg once daily for 7 days. We showed that the P2Y12R was markedly activated after injury, and it was double labeled with the microglial and neuron. Behavioral tests were employed to assess motor function recovery. By using immunofluorescence staining, the NeuN expression level was detected. The morphology of neurons was observed by hematoxylin-eosin and Nissl staining. P2Y12R, Bax, GFAP, PCNA and calbindin expression levels were detected using Western blot. Meanwhile, mitochondria and myelin sheath were observed by transmission electron microscopy (TEM). Our findings demonstrated that MRS2395 significantly enhanced motor function induced by SCI and that was used to alleviate apoptosis and astrocyte scarring. NeuN positive cells in the SCI group were lower than in the therapy group, although Bax, GFAP, PCNA and calbindin expression levels were considerably higher. Moreover, following MRS2395 therapy, the histological damage was reversed. A notable improvement in myelin sheath and mitochondrial morphology was seen in the therapy group. Together, our findings indicate that activation of P2Y12R in damaged spinal cord may be a critical event and suggest that inhibition of P2Y12R might be a feasible therapeutic strategy for treating SCI.
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Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Traumatismos de la Médula Espinal
/
Enfermedades Desmielinizantes
Límite:
Animals
Idioma:
En
Revista:
Neurochem Int
Año:
2023
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Reino Unido