Unravelling a novel role for Cannabidivarin in the modulation of subventricular zone postnatal neurogenesis
Unravelling a novel role for Cannabidivarin in the modulation of subventricular zone postnatal neurogenesis
Abstract Postnatal neurogenesis has been shown to rely on the endocannabinoid system. Here we aimed at unravelling the role of Cannabidivarin (CBDV), a non-psychoactive cannabinoid, with high affinity for the non-classical cannabinoid receptor TRPV1, on subventricular zone (SVZ) postnatal neurogenesis. Using the neurosphere assay, SVZ-derived neural stem/progenitor cells (NSPCs) were incubated with CBDV and/or 5’-Iodoresinferotoxin (TRPV1 antagonist), and their role on cell viability, proliferation, and differentiation were dissected. CBDV was able to promote, through a TRPV1-dependent mechanism, cell survival, cell proliferation and neuronal differentiation. Furthermore, pulse-chase experiments revealed that CBDV-induced neuronal differentiation was a result of cell cycle exit of NSPCs. Regarding oligodendrocyte differentiation, CBDV inhibited oligodendrocyte differentiation and maturation. Since our data suggested that the CBDV-induced modulation of NSPCs acted via TRPV1, a sodium-calcium channel, and that intracellular calcium levels are known regulators of NSPCs fate and neuronal maturation, single cell calcium imaging was performed to evaluate the functional response of SVZ-derived cells. We observed that CBDV-responsive cells displayed a two-phase calcium influx profile, being the initial phase dependent on TRPV1 activation. Taken together, this work unveiled a novel and untapped neurogenic potential of CBDV via TRPV1 modulation. These findings pave the way to future neural stem cell biological studies and repair strategies by repurposing this non-psychoactive cannabinoid as a valuable therapeutic target.
Sol¨￠ Susana、Louren?o Diogo M.、Santos S¨?nia S¨￠、Xapelli Sara、Sebasti?o Ana M.、Rodrigues Rui S.、Moreira Jo?o B.、Vaz Sandra H.、Mateus Joana M.、Soares Rita
Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm¨￠cia, Universidade de LisboaInstituto de Farmacologia e Neuroci¨oncias, Faculdade de Medicina, Universidade de Lisboa||Instituto de Medicina Molecular Jo?o Lobo Antunes, Faculdade de Medicina, Universidade de LisboaResearch Institute for Medicines (iMed.ULisboa), Faculdade de Farm¨￠cia, Universidade de LisboaInstituto de Farmacologia e Neuroci¨oncias, Faculdade de Medicina, Universidade de Lisboa||Instituto de Medicina Molecular Jo?o Lobo Antunes, Faculdade de Medicina, Universidade de LisboaInstituto de Farmacologia e Neuroci¨oncias, Faculdade de Medicina, Universidade de Lisboa||Instituto de Medicina Molecular Jo?o Lobo Antunes, Faculdade de Medicina, Universidade de LisboaInstituto de Farmacologia e Neuroci¨oncias, Faculdade de Medicina, Universidade de Lisboa||Instituto de Medicina Molecular Jo?o Lobo Antunes, Faculdade de Medicina, Universidade de LisboaInstituto de Farmacologia e Neuroci¨oncias, Faculdade de Medicina, Universidade de Lisboa||Instituto de Medicina Molecular Jo?o Lobo Antunes, Faculdade de Medicina, Universidade de LisboaInstituto de Farmacologia e Neuroci¨oncias, Faculdade de Medicina, Universidade de Lisboa||Instituto de Medicina Molecular Jo?o Lobo Antunes, Faculdade de Medicina, Universidade de LisboaInstituto de Farmacologia e Neuroci¨oncias, Faculdade de Medicina, Universidade de Lisboa||Instituto de Medicina Molecular Jo?o Lobo Antunes, Faculdade de Medicina, Universidade de LisboaInstituto de Farmacologia e Neuroci¨oncias, Faculdade de Medicina, Universidade de Lisboa||Instituto de Medicina Molecular Jo?o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa||Instituto de Biologia Molecular, Faculdade de Medicina, Universidade de Lisboa
基础医学神经病学、精神病学药学
Adult neurogenesisCannabidivarinTRPV1Neural stem cellsOligodendrogenesisSubventricular Zone
Sol¨￠ Susana,Louren?o Diogo M.,Santos S¨?nia S¨￠,Xapelli Sara,Sebasti?o Ana M.,Rodrigues Rui S.,Moreira Jo?o B.,Vaz Sandra H.,Mateus Joana M.,Soares Rita.Unravelling a novel role for Cannabidivarin in the modulation of subventricular zone postnatal neurogenesis[EB/OL].(2025-03-28)[2025-05-17].https://www.biorxiv.org/content/10.1101/2023.05.16.540990.点此复制
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