20.500.12556/RUL-178100 Cannabinoid ligand-mediated glycogen depletion in astrocytes is associated with increased intracellular calcium, energy metabolism, and membrane dynamics Astrocytes orchestrate brain energy metabolism and respond to endocannabinoids via cannabinoid receptor type 1 (CB1R), whereas the contribution of CB2R remains uncertain. We combined live-cell Förster resonance energy transfer sensors for D-glucose and L-lactate, intracellular Ca$^{2+}$ imaging, glycogen assays, and whole-cell patch-clamp capacitance measurements to define how cannabinoid ligands shape astrocyte physiology in primary rat cultures. The CB1-selective agonist ACEA triggered rapid, transient elevations in [Ca$^{2+}$]ᵢ and metabolic readouts, whereas the CB2-biased ligands AM1241 and Gp1a produced sustained metabolic effects, including prolonged increases in intracellular D-glucose and L-lactate. AM1241 additionally evoked glycogen depletion. Ligand applications also increased membrane capacitance, consistent with enhanced exocytotic activity and altered membrane dynamics. CB1 immunoreactivity predominated over a weak CB2-like signal, and RT-qPCR detected Cnr1 but not Cnr2 transcripts under our conditions. Accordingly, we interpret AM1241/Gp1a actions as ligand-evoked effects that are predominantly CB1-linked (and/or off-target at the concentrations used). Together, these results show that cannabinoid ligands robustly remodel astrocytic energy metabolism and membrane behavior chiefly through CB1-associated pathways, highlighting a functional axis between cannabinoid signaling, Ca$^{2+}$ mobilization, glycogen remodeling, and exocytosis in astrocytes. astrocytes calcium signaling cannabinoid receptors exocytosis glucose metabolism lactate astrociti kalcijevo signaliziranje kanabinoidni receptorji eksocitoza presnova glukoze laktat true false true Angleški jezik Slovenski jezik Članek v reviji 2026-01-19 08:47:03 2026-01-19 08:47:03 2026-02-03 04:26:07 0000-00-00 00:00:00 2025 0 0 Objavljen je popravek tega članka (gl. datoteko Priloga – Erratum): Journal of neurochemistry, 2026, vol. 170, iss. 1, art. e70370, DOI: https://doi.org/10.1111/jnc.70370. 15 str. iss. 12, art. e70332 Vol. 169 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.8 1471-4159 10.1111/jnc.70332 265140227 RAZ_Fink_Katja_2025.pdf RAZ_Fink_Katja_2025.pdf 1 872B4B7A86CE849278D89B89986A1A8A 44124679cd48033a2b5c04b4137640e1beb3998da8d3d0073bf24f3a8fd8643e 24dea788-f50b-11f0-bf92-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=225642 AAM_Correction_to_JNC_70332_mk.pdf AAM_Correction_to_JNC_70332_mk.pdf Erratum Erratum 1 7CC26880FD25A3690F3BD3FC851C0D32 7b6370978b1e8f4841bc9dfc4b9164bfe03be1133c699ecfc15155a9f9c167e2 98a9426b-000a-11f1-a1ba-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=226965 https://onlinelibrary.wiley.com/doi/10.1111/jnc.70332 0 0f70b9ce-f50b-11f0-bf92-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=225641 Medicinska fakulteta Biotehniška fakulteta 0 0 0