|国家预印本平台
首页|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

Unravelling a novel role for Cannabidivarin in the modulation of subventricular zone postnatal neurogenesis

来源:bioRxiv_logobioRxiv
英文摘要

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

10.1101/2023.05.16.540990

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

评论