ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1654664
This article is part of the Research TopicNeuroinflammation: Mechanisms and Therapeutic InterventionsView all 15 articles
Golexanolone affords sustained microglia and astrocytes activation improvement in a rat model of Parkinson's disease
Provisionally accepted
Gergana Mincheva1
Maria A Pedrosa1Mar Martinez-Garcia1Lola Vazquez1Thomas P Blackburn2
Magnus Doverskog2
MARTA LLANSOLA1*
Vicente Felipo1- 1Principe Felipe Research Center (CIPF), Valencia, Spain
- 2Umecrine Cognition AB, Solna, Sweden
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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 (TNFα, IL-1α, 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. 6-OHDA rats show pro-inflammatory microglia in SN and striatum, with reduced area and increased TNFα at 3 and 9 weeks, increased TNFα, IL-1α and HMGB1 and pro-inflammatory A1 astrocytes activation with increased GFAP, vimentin and S100Β and reduced S100A10. Golexanolone reversed microglia activation, the increase in pro-inflammatory factors and astrocytes A1 activation both at 3 and 9 weeks. Sustained improvement of glial activation in SN and striatum would be a key mechanism in the improvement of PD symptoms by golexanolone.
Keywords: golexanolone, Parkinson's disease, Neuroinflammation, Vimentin, microglia activation, Astrocyte activation, Striatum, Substantia Nigra
Received: 26 Jun 2025; Accepted: 20 Aug 2025.
Copyright: © 2025 Mincheva, Pedrosa, Martinez-Garcia, Vazquez, Blackburn, Doverskog, LLANSOLA and Felipo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: MARTA LLANSOLA, Principe Felipe Research Center (CIPF), Valencia, Spain
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