Dataset Information

?⁹ -Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo.

ABSTRACT: ?⁹ -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.

SUBMITTER: Huerga-Gomez A

PROVIDER: S-EPMC7821226 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Δ<sup>9</sup> -Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo.

Huerga-Gómez Alba A Aguado Tania T Sánchez-de la Torre Aníbal A Bernal-Chico Ana A Matute Carlos C Mato Susana S Guzmán Manuel M Galve-Roperh Ismael I Palazuelos Javier J

Glia 20200921 3

Δ<sup>9</sup> -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 ...[more]

PMID: 32956517

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Project description:Oligodendrocyte differentiation and central nervous system myelination require massive reorganization of the oligodendrocyte cytoskeleton. Loss of specific actin- and tubulin-organizing factors can lead to impaired morphological and/or molecular differentiation of oligodendrocytes, resulting in a subsequent loss of myelination. Dystonin is a cytoskeletal linker protein with both actin- and tubulin-binding domains. Loss of function of this protein results in a sensory neuropathy called Hereditary Sensory Autonomic Neuropathy VI in humans and dystonia musculorum in mice. This disease presents with severe ataxia, dystonic muscle and is ultimately fatal early in life. While loss of the neuronal isoforms of dystonin primarily leads to sensory neuron degeneration, it has also been shown that peripheral myelination is compromised due to intrinsic Schwann cell differentiation abnormalities. The role of this cytoskeletal linker in oligodendrocytes, however, remains unclear. We sought to determine the effects of the loss of neuronal dystonin on oligodendrocyte differentiation and central myelination. To address this, primary oligodendrocytes were isolated from a severe model of dystonia musculorum, Dstdt-27J, and assessed for morphological and molecular differentiation capacity. No defects could be discerned in the differentiation of Dstdt-27J oligodendrocytes relative to oligodendrocytes from wild-type littermates. Survival was also compared between Dstdt-27J and wild-type oligodendrocytes, revealing no significant difference. Using a recently developed migration assay, we further analysed the ability of primary oligodendrocyte progenitor cell motility, and found that Dstdt-27J oligodendrocyte progenitor cells were able to migrate normally. Finally, in vivo analysis of oligodendrocyte myelination was done in phenotype-stage optic nerve, cerebral cortex and spinal cord. The density of myelinated axons and g-ratios of Dstdt-27J optic nerves was normal, as was myelin basic protein expression in both cerebral cortex and spinal cord. Together these data suggest that, unlike Schwann cells, oligodendrocytes do not have an intrinsic requirement for neuronal dystonin for differentiation and myelination.

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?⁹ -Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo.

Publications

Δ<sup>9</sup> -Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo.

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Dataset Information

?9 -Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo.

Publications

Δ<sup>9</sup> -Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

?⁹ -Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo.