Chronic exercise modulates the cellular immunity and its cannabinoid receptors expression

Valencia-Sánchez, Salvador; Nava-Castro, Karen Elizabeth; Palacios-Arreola, Margarita Isabel; Prospéro-Garcı́a, Oscar; Morales‐Montor, Jorge; Drucker-Colı́n, René

doi:10.1371/journal.pone.0220542

Cited by 6 publications

(3 citation statements)

References 45 publications

(49 reference statements)

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“…We posit that, in our experimental conditions, CB2R inhibition may be shielding the system against stress-targeted reactive microglia (which express high levels of CB2Rs [ 97 ]), thus facilitating PE actions in limiting the neuroinflammatory damage caused by chronic stress. Conversely, PE may be modulating stress-disrupted cellular immunity and CB2R inhibition further alleviating this immunoinflammatory status [ 98 ].…”

Section: Discussionmentioning

confidence: 99%

Cannabinoid type 2 receptor inhibition enhances the antidepressant and proneurogenic effects of physical exercise after chronic stress

Rodrigues,

Moreira,

Mateus

et al. 2024

Transl Psychiatry

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Chronic stress is a major risk factor for neuropsychiatric conditions such as depression. Adult hippocampal neurogenesis (AHN) has emerged as a promising target to counteract stress-related disorders given the ability of newborn neurons to facilitate endogenous plasticity. Recent data sheds light on the interaction between cannabinoids and neurotrophic factors underlying the regulation of AHN, with important effects on cognitive plasticity and emotional flexibility. Since physical exercise (PE) is known to enhance neurotrophic factor levels, we hypothesised that PE could engage with cannabinoids to influence AHN and that this would result in beneficial effects under stressful conditions. We therefore investigated the actions of modulating cannabinoid type 2 receptors (CB2R), which are devoid of psychotropic effects, in combination with PE in chronically stressed animals. We found that CB2R inhibition, but not CB2R activation, in combination with PE significantly ameliorated stress-evoked emotional changes and cognitive deficits. Importantly, this combined strategy critically shaped stress-induced changes in AHN dynamics, leading to a significant increase in the rates of cell proliferation and differentiation of newborn neurons, overall reduction in neuroinflammation, and increased hippocampal levels of BDNF. Together, these results show that CB2Rs are crucial regulators of the beneficial effects of PE in countering the effects of chronic stress. Our work emphasises the importance of understanding the mechanisms behind the actions of cannabinoids and PE and provides a framework for future therapeutic strategies to treat stress-related disorders that capitalise on lifestyle interventions complemented with endocannabinoid pharmacomodulation.

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Section: Discussionmentioning

confidence: 99%

Cannabinoid type 2 receptor inhibition enhances the antidepressant and proneurogenic effects of physical exercise after chronic stress

Rodrigues,

Moreira,

Mateus

et al. 2024

Transl Psychiatry

View full text Add to dashboard Cite

show abstract

“…We posit that, in our experimental conditions, CB2R inhibition may be shielding the system against stress-targeted reactive microglia (which express high levels of CB2Rs [87]), thus facilitating PE actions in limiting the neuroinflammatory damage caused by chronic stress. Conversely, PE may be modulating stress-disrupted cellular immunity and CB2R inhibition further alleviating this immunoinflammatory status [88].…”

Section: Discussionmentioning

confidence: 99%

Cannabinoid type 2 receptor inhibition enhances the antidepressant and proneurogenic effects of physical exercise after chronic stress

Rodrigues

Moreira

Vaz

et al. 2023

Preprint

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Chronic stress is a major risk factor of neuropsychiatric conditions such as depression. Adult hippocampal neurogenesis (AHN) has emerged as a promising target to counteract stress-related disorders given the ability of newborn neurons to facilitate endogenous plasticity. Recent data sheds light on the interaction between cannabinoids and neurotrophic factors underlying the regulation of AHN, with important effects upon cognitive plasticity and emotional flexibility. Since physical exercise (PE) is known to enhance neurotrophin levels, we hypothesized that PE could engage with cannabinoids to influence AHN and that this would result in beneficial effects under stressful conditions. We therefore investigated the actions of modulating cannabinoid type 2 receptors (CB2R), which are devoid of psychotropic effects, in combination with PE in chronically stressed animals. We found that CB2R inhibition, but not CB2R activation, in combination with PE significantly ameliorated stress-evoked emotional changes and cognitive deficits. Importantly, this combined strategy critically shaped stress-induced changes in AHN dynamics, leading to a significant increase in the rates of cell proliferation and differentiation of newborn neurons, and an overall reduction in neuroinflammation. Together, these results show that CB2Rs are crucial regulators of the beneficial effects of PE in countering the effects of chronic stress. Our work emphasizes the importance of understanding the mechanisms behind the actions of cannabinoids and PE and provides a framework for future therapeutic strategies to treat stress-related disorders that capitalize on lifestyle interventions complemented with endocannabinoid pharmacomodulation.

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“…CBD’s effects are mainly exerted through action on cannabinoid receptors type 1 (CB1R) and type 2 (CB2R) [ 27 ]. CB1 receptors are mainly expressed in the central nervous system (CNS) [ 28 ], whereas CB2 ones are mainly present on immune cells such as polymorphonuclear leukocytes (PMNs) and lymphocytes [ 29 , 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Cannabidiol on Innate Immunity: Experimental Evidence and Clinical Relevance

Martini

Gemma

Ferrari

et al. 2023

IJMS

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Cannabidiol (CBD) is the main non-psychotropic cannabinoid derived from cannabis (Cannabis sativa L., fam. Cannabaceae). CBD has received approval by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of seizures associated with Lennox–Gastaut syndrome or Dravet syndrome. However, CBD also has prominent anti-inflammatory and immunomodulatory effects; evidence exists that it could be beneficial in chronic inflammation, and even in acute inflammatory conditions, such as those due to SARS-CoV-2 infection. In this work, we review available evidence concerning CBD’s effects on the modulation of innate immunity. Despite the lack so far of clinical studies, extensive preclinical evidence in different models, including mice, rats, guinea pigs, and even ex vivo experiments on cells from human healthy subjects, shows that CBD exerts a wide range of inhibitory effects by decreasing cytokine production and tissue infiltration, and acting on a variety of other inflammation-related functions in several innate immune cells. Clinical studies are now warranted to establish the therapeutic role of CBD in diseases with a strong inflammatory component, such as multiple sclerosis and other autoimmune diseases, cancer, asthma, and cardiovascular diseases.

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Chronic exercise modulates the cellular immunity and its cannabinoid receptors expression

Cited by 6 publications

References 45 publications

Cannabinoid type 2 receptor inhibition enhances the antidepressant and proneurogenic effects of physical exercise after chronic stress

Cannabinoid type 2 receptor inhibition enhances the antidepressant and proneurogenic effects of physical exercise after chronic stress

Cannabinoid type 2 receptor inhibition enhances the antidepressant and proneurogenic effects of physical exercise after chronic stress

Effects of Cannabidiol on Innate Immunity: Experimental Evidence and Clinical Relevance

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