Connexin43 inhibition attenuated dopaminergic neuronal loss in the lipopolysaccharide-induced mice model of Parkinson's disease.
Neurosci Lett
; 771: 136471, 2022 02 06.
Article
en En
| MEDLINE
| ID: mdl-35065246
ABSTRACT
Studies using in vitro Parkinson's disease (PD) models have found that lipopolysaccharide (LPS) induced reduction of connexin 43 (Cx43) gap junction communication and elevation of hemichannel function, which could cause neurotoxicity directly and indirectly via excessive ATP and glutamate release. However, in vivo study about Cx43 expression and function, as well as the efficacy of Cx43 inhibition for neuronal survival in PD is lacking. This study aimed to unravel the role of Cx43 in PD and understand the underlying mechanisms using an in vivo PD model. Male C57BL/6 mice received intranigral injection of LPS (5 µg) and 43Gap27 (4 µg), a Cx43 inhibitor, simultaneously. Results showed that following LPS treatment, total Cx43 expression decreased by about 60%, but the relative level of phosphorylated Cx43 increased to about double that controls (all p < 0.05). The administration of 43Gap27 significantly attenuated the loss of dopaminergic neurons and restored dopamine and its metabolites levels. Moreover, 43Gap27 treatment inhibited intense microgliosis and astrogliosis in nigrostriatal system induced by LPS and also ameliorated elevated levels of inflammatory mediators. Interestingly, Cx43 inhibition also increased nerve growth factors. In conclusion, Cx43 inhibition was able to prevent LPS-mediated dopaminergic neuronal death, possibly via neuroinflammation reaction reduction and neurotrophic factors elevation. Therefore, Cx43 may be a promising therapeutic target for degenerative neurological disorders such as PD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Enfermedad de Parkinson
/
Conexinas
/
Conexina 43
/
Neuronas Dopaminérgicas
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neurosci Lett
Año:
2022
Tipo del documento:
Article
País de afiliación:
Países Bajos