Details

Autor(en) / Beteiligte

• Rodríguez-Cueto, Carmen
• Santos-García, Irene
• García-Toscano, Laura
• Espejo-Porras, Francisco
• Bellido, MLuz
• Fernández-Ruiz, Javier
• Muñoz, Eduardo
• de Lago, Eva

Titel

Neuroprotective effects of the cannabigerol quinone derivative VCE-003.2 in SOD1 G93A transgenic mice, an experimental model of amyotrophic lateral sclerosis

Ist Teil von

• Biochemical pharmacology, 2018-11, Vol.157, p.217

Ort / Verlag

England

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Antioxidant phytocannabinoids, synthetic compounds targeting the CB receptor, and inhibitors of the endocannabinoid inactivation afforded neuroprotection in SOD1 mutant mice, a model of ALS. These effects may involve the activation of PPAR-γ too. Here, we have investigated the neuroprotective effects in SOD1 mutant mice of the cannabigerol derivative VCE-003.2, which works as neuroprotectant by activating PPAR-γ. Mice were treated with VCE-003.2 from 60 days up to an advanced stage in disease progression (18 weeks), when they were euthanized and used for analysis of neuropathological signs. As expected, SOD1 transgenic mice experienced a progressive weight loss and neurological deterioration, which was associated with a marked loss of spinal cholinergic motor neurons, glial reactivity, and elevations in several biochemical markers (cytokines, glutamate transporters) that indirectly reflect the glial proliferation and activation in the spinal cord. The treatment with VCE-003.2 improved most of these neuropathological signs. It attenuated the weight loss and the anomalies in neurological parameters, preserved spinal cholinergic motor neurons, and reduced astroglial reactivity. VCE-003.2 also reduced the elevations in IL-1β and glial glutamate transporters. Lastly, VCE-003.2 attenuated the LPS-induced generation of TNF-α and IL-1β in cultured astrocytes obtained from SOD1 transgenic newborns, an effect also produced by rosiglitazone, then indicating a probable PPAR-γ activation as responsible of its neuroprotective effects. In summary, our results showed benefits with VCE-003.2 in SOD1 transgenic mice supporting PPAR-γ as an additional neuroprotective target available for cannabinoids in ALS. Such benefits would need to be validated in other ALS models prior to be translated to the clinical level.