Δ9-Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo

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Huerga-Gómez, Alba and Aguado, Tania and Sánchez de la Torre, Aníbal and Bernal-Chico, Ana and Matute, Carlos and Mato, Susana and Guzmán, Manuel and Galve-Roperh, Ismael and Palazuelos Diego, Javier (2020) Δ9-Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo. Glia, 69 (3). pp. 532-545. ISSN 0894-1491; Electronic: 1098-1136

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Official URL: https://onlinelibrary.wiley.com/doi/10.1002/glia.23911



Abstract

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.


Item Type:Article
Uncontrolled Keywords:Cannabinoid receptors; Cannabinoids; CB1; CB2; mTORC1; Myelination; Oligodendrocyte; Precursor cells
Subjects:Medical sciences > Biology > Biochemistry
Medical sciences > Biology > Neurosciences
ID Code:65646
Deposited On:21 May 2021 08:30
Last Modified:24 May 2021 07:53

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