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cc-by (c) Borràs Pernas, Sara et al., 2025
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/228536

Low-dose cannabidiol treatment prevents chronic stress-induced phenotypes and is associated with multiple synaptic changes across various brain regions

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Major Depressive Disorder (MDD) is a heterogeneous and debilitating mood disorder often associated with stress. Although current treatments are available, they remain ineffective for approximately 30 % of affected individuals and are frequently accompanied by undesirable side effects. Cannabidiol (CBD) has emerged as a potential and safe therapeutic option for alleviating depressive symptoms; however, the underlying molecular mechanisms through which this compound exerts its beneficial effects are not yet fully understood. In this study, we demonstrate that a very low dose of CBD (1 mg/kg) can partially reverse some sequelae induced by chronic stress, a well-established mouse model used to simulate depressive-like symptoms. Using mass spectrometry to analyze different brain regions, we observed several improvements following CBD treatment, particularly in the medial prefrontal cortex (mPFC), across multiple neurotransmission systems (including glutamatergic and serotonergic pathways). Microstructural experiments, utilizing double-labeling of F-Actin and VGlut1-positive clusters, revealed a complete restoration of mature synapses in the mPFC of mice treated with CBD. In conclusion, our findings indicate that a very low dose of CBD is effective in counteracting the adverse effects of chronic stress, possibly through the synaptic remodeling of excitatory synapses in the mPFC.

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BORRÀS PERNAS, Sara, SANCHO BALSELLS, Anna, PATTERER, Lisa, WANG, Maoyu, TORO RUIZ, Daniel del, ALBERCH I VIÉ, Jordi, SCHIBANO, Daniele, ESPEL, Joan, HEYBECK, Maya, SCHEIDEL, Bernhard, GIRALT TORROELLA, Albert. Low-dose cannabidiol treatment prevents chronic stress-induced phenotypes and is associated with multiple synaptic changes across various brain regions. _Neuropharmacology_. 2025. Vol. 277. [consulta: 2 de abril de 2026]. ISSN: 0028-3908. [Disponible a: https://hdl.handle.net/2445/228536]

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