The protective effects of nesfatin-1 in neurological dysfunction after spinal cord injury by inhibiting neuroinflammation.
Brain Behav
; 12(11): e2778, 2022 11.
Article
en En
| MEDLINE
| ID: mdl-36271663
ABSTRACT
AIMS:
Spinal cord injury (SCI) is one of the most severe neurological diseases. However, there is still no effective treatment for it. Nesfatin, a precursor neuropeptide derived from nucleobindin 2 (NUCB2), has displayed a wide range of protective effects in different types of cells and tissue. However, the effects of nesfatin-1 in SCI have not been reported before. MATERIALS ANDMETHODS:
A SCI model was established. The behavior of mice was assessed using the Basso, Beattie, and Bresnahan (BBB) assessment.RESULTS:
Here, we report that the administration of nesfatin-1 improved neurological recovery in SCI mice by increasing BBB scores, reducing lesion area volume and spinal cord water content. Also, nesfatin-1 ameliorated oxidative stress by reducing reactive oxygen species (ROS) levels and increasing superoxide dismutase (SOD) activity. We also found that nesfatin-1 prevented neuronal apoptosis in SCI mice by reducing caspase 3 activity and the expression of Bax, as well as increasing B-cell lymphoma-2 (Bcl-2). Additionally, nesfatin-1 reduced the levels of interleukin 6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α). Nesfatin-1 also promoted microglia towards M2 polarization by increasing the marker CD206 but reducing CD16. Importantly, nesfatin-1 enhanced the phosphorylation of signal transducer and activator of transcription 1 (STAT1) but reduced the expression levels of toll-like receptor 4 (TLR4) and phosphorylated nuclear factor kappa-B p65 (p-NF-κB p65).CONCLUSION:
Our findings imply that nesfatin-1 exerts neuroprotective actions in SCI by promoting the activation of M2 microglia, and its underlying mechanisms might be related to the activation of STAT1 and inhibition of the TLR4/NF-κB signaling pathway.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Traumatismos de la Médula Espinal
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Nucleobindinas
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Enfermedades Neuroinflamatorias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Brain Behav
Año:
2022
Tipo del documento:
Article
País de afiliación:
China