Golexanolone affords sustained microglia and astrocytes activation improvement in a rat model of Parkinson's disease
Introduction Golexanolone improves motor and non-motor alterations in the unilateral 6-OHDA rat model of PD. We hypothesized that a key mechanism by which golexanolone induces these beneficial effects is by reducing microglia activation, thus reducing pro-inflammatory factors (TNF alpha, IL-1 alpha,...
| Autores: | , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Centro de Investigación Principe Felipe (CIPF) |
| Repositorio: | r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF) |
| OAI Identifier: | oai:cipf.fundanetsuite.com:p4506 |
| Acceso en línea: | https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=4506 |
| Access Level: | acceso abierto |
| Palabra clave: | golexanolone Parkinson's disease neuroinflammation vimentin microglia activation astrocyte activation striatum substantia nigra |
| Sumario: | Introduction Golexanolone improves motor and non-motor alterations in the unilateral 6-OHDA rat model of PD. We hypothesized that a key mechanism by which golexanolone induces these beneficial effects is by reducing microglia activation, thus reducing pro-inflammatory factors (TNF alpha, IL-1 alpha, HMGB1) which activate astrocytes. This work aims were to assess if golexanolone affords sustained improvement of glial activation and pro-inflammatory factors at 3 and 9 weeks after 6-OHDA injection.Results 6-OHDA rats show pro-inflammatory microglia in SN and striatum, with reduced area and increased TNF alpha at 3 and 9 weeks, increased TNF alpha, IL-1 alpha and HMGB1 and pro-inflammatory A1 astrocytes activation with increased GFAP, vimentin and S100B and reduced S100A10. Golexanolone reversed microglia activation, the increase in pro-inflammatory factors and astrocytes A1 activation both at 3 and 9 weeks. Golexanolone reversed microglia activation, the increase in pro-inflammatory factors and astrocytes A1 activation both at 3 and 9 weeks.Discussion Sustained improvement of glial activation in SN and striatum would be a key mechanism in the improvement of PD symptoms by golexanolone. |
|---|