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Introduction: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Although the precise pathogenesis of PD remains unclear, several studies demonstrate that oxidative stress, inflammation, low levels of antioxidants, and the presence of biomolecules that generate reactive oxygen species can disrupt the blood-brain barrier (BBB) as an essential feature of the disease., Aims: This study aimed to test whether agonism to cannabinoid receptor type 2 (CB2) through the administration of β-caryophyllene (BCP) could correct BBB permeability in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonism induction model., Methods: We conducted a molecular assessment of proteins (immunochemistry and western blot), BBB permeability, and related biomarkers of PD (lipid peroxidation) in the MPTP mouse model of the disease., Results: Expression of zonula occludens (ZO-1) and occludin tight junction (TJ) proteins was dampened in the striatum and substantia nigra pars compacta of mice, while lipid peroxidation and BBB permeability increased in the striatum in the MPTP-treated group, and these effects were reversed under BCP administration. This phytocannabinoid was able to restore protein expression and immunoreactivity of tyrosine hydroxylase (TH), ionized calcium-binding adapter molecule 1 (Iba-1), and glial fibrillary acidic protein (GFAP), as well as nuclear factor-erythroid 2-related factor (NRF2) translocation to the nucleus, and NADPH quinone oxidase 1 (NQO1) expression in mice treated with MPTP., Conclusion: These results highlight the role of CB2 as a therapeutic target for PD, suggesting that its activation may ameliorate PD-related BBB disruption and oxidative stress, reducing the selective death of dopaminergic neurons., (Copyright © 2023 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Over time, several studies have been conducted to demonstrate the functions of the neurotransmitter 5-hydroxytryptamine (5-HT), better known as serotonin. This neurotransmitter is associated with the modulation of various social and physiological behaviors, and its dysregulation has consequences at the behavioral level, leading to various neurophysiological disorders. Disorders such as anxiety, depression, schizophrenia, epilepsy, sexual disorders, and eating disorders, have been closely linked to variations in 5-HT concentrations and modifications in brain structures, including the raphe nuclei (RN), prefrontal cortex, basal ganglia, hippocampus, and hypothalamus, among others. The involvement of β-arrestin proteins has been implicated in the modulation of the serotonergic receptor response, as well as the activation of different signaling pathways related to the serotonergic system, this is particularly relevant in depressive disorders. This review will cover the implications of alterations in 5-HT receptor expression in depressive disorders in one hand and how β-arrestin proteins modulate the response mediated by these receptors in the other hand., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)