4.5 Article

Cannabidiol Recovers Dopaminergic Neuronal Damage Induced by Reserpine or α-synuclein in Caenorhabditis elegans

Journal

NEUROCHEMICAL RESEARCH
Volume 48, Issue 8, Pages 2390-2405

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-023-03905-z

Keywords

Parkinson Disease; Caenorhabditis elegans; Cannabidiol

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In this study, the potential neuroprotective effect of cannabidiol (CBD) in the treatment of Parkinson's Disease (PD) was evaluated using a C. elegans model. The results showed that CBD could reverse locomotor alterations induced by reserpine and protect neurons from degeneration. Additionally, CBD also reduced the formation of reactive oxygen species (ROS) and accumulation of alpha-synuclein protein. These findings indicate that CBD acts as a neuroprotector in dopaminergic neurons and highlights its potential in the treatment of PD.
Progressive neurodegenerative disorders such as Parkinson Disease (PD) lack curative or long-term treatments. At the same time, the increase of the worldwide elderly population and, consequently, the extension in the prevalence of age-related diseases have promoted research interest in neurodegenerative disorders. Caenorhabditis elegans is a free-living nematode widely used as an animal model in studies of human diseases. Here we evaluated cannabidiol (CBD) as a possible neuroprotective compound in PD using the C. elegans models exposed to reserpine. Our results demonstrated that CBD reversed the reserpine-induced locomotor alterations and this response was independent of the NPR-19 receptors, an orthologous receptor for central cannabinoid receptor type 1. Morphological alterations of cephalic sensilla (CEP) dopaminergic neurons indicated that CBD also protects neurons from reserpine-induced degeneration. That is, CBD attenuates the reserpine-induced increase of worms with shrunken soma and dendrites loss, increasing the number of worms with intact CEP neurons. Finally, we found that CBD also reduced ROS formation and alpha-syn protein accumulation in mutant worms. Our findings collectively provide new evidence that CBD acts as neuroprotector in dopaminergic neurons, reducing neurotoxicity and alpha-syn accumulation highlighting its potential in the treatment of PD.

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