Golexanolone affords sustained microglia and astrocytes activation improvement in a rat model of Parkinson's disease
Por:
G. MINCHEVA, M. PEDROSA, M. VÁZQUEZ, L. VAZQUEZ, T. BLACKBURN, M. DOVERSKOG, M. LLANSOLA and V. FELIPO
Publicada:
3 sep 2025
Resumen:
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.
Filiaciones:
:
Ctr Invest Principe Felipe, Lab Neurobiol, Valencia, Spain
M. PEDROSA:
Ctr Invest Principe Felipe, Lab Neurobiol, Valencia, Spain
L. VAZQUEZ:
Ctr Invest Principe Felipe, Lab Neurobiol, Valencia, Spain
T. BLACKBURN:
Umecrine Cognit AB, Solna, Sweden
M. DOVERSKOG:
Umecrine Cognit AB, Solna, Sweden
:
Ctr Invest Principe Felipe, Lab Neurobiol, Valencia, Spain
:
Ctr Invest Principe Felipe, Lab Neurobiol, Valencia, Spain
Green Submitted, gold
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