RT Journal Article
T1 Δ9-Tetrahydrocannabinol promotes oligodendrocytedevelopment and CNS myelination in vivo
A1 Huerga-Gómez, Alba
A1 Aguado, Tania
A1 Sánchez de la Torre, Aníbal
A1 Bernal-Chico, Ana
A1 Matute, Carlos
A1 Mato, Susana
A1 Guzmán, Manuel
A1 Galve-Roperh, Ismael
A1 Palazuelos Diego, Javier
AB Δ9 -Tetrahydrocannabinol (THC), the main bioactive compound found in the plant Cannabis sativa, exerts its effects by activating cannabinoid receptors present in many neural cells. Cannabinoid receptors are also physiologically engaged by endogenous cannabinoid compounds, the so-called endocannabinoids. Specifically, the endocannabinoid 2-arachidonoylglycerol has been highlighted as an important modulator of oligodendrocyte (OL) development at embryonic stages and in animal models of demyelination. However, the potential impact of THC exposure on OL lineage progression during the critical periods of postnatal myelination has never been explored. Here, we show that acute THC administration at early postnatal ages in mice enhanced OL development and CNS myelination in the subcortical white matter by promoting oligodendrocyte precursor cell cycle exit and differentiation. Mechanistically, THC-induced-myelination was mediated by CB1 and CB2 cannabinoid receptors, as demonstrated by the blockade of THC actions by selective receptor antagonists. Moreover, the THC-mediated modulation of oligodendroglial differentiation relied on the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, as mTORC1 pharmacological inhibition prevented the THC effects. Our study identifies THC as an effective pharmacological strategy to enhance oligodendrogenesis and CNS myelination in vivo.
PB Wiley
SN 0894-1491; Electronic: 1098-1136
YR 2020
FD 2020-09-21
LK https://hdl.handle.net/20.500.14352/8144
UL https://hdl.handle.net/20.500.14352/8144
LA eng
NO Ministerio de Economía y Competitividad (MINECO)
NO Comunidad de Madrid
NO Instituto de Salud Carlos III (ISCIII)/Fondo Europeo de Desarrollo Regional (FEDER)
NO Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED)
NO Eusko Jaurlaritza
NO Fundación Tatiana Pérez de Guzmán el Bueno
DS Docta Complutense
RD 15 may 2024