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Regulatory role of the cannabinoid CB2 receptor in stress‐induced neuroinflammation in mice

Zoppi, S ; Madrigal, J L ; Caso, J R ; García‐Gutiérrez, M S ; Manzanares, J ; Leza, J C ; García‐Bueno, B

British journal of pharmacology, 2014-06, Vol.171 (11), p.2814-2826 [Periódico revisado por pares]

England: Blackwell Publishing Ltd

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Título:
Regulatory role of the cannabinoid CB2 receptor in stress‐induced neuroinflammation in mice
Autor: Zoppi, S ; Madrigal, J L ; Caso, J R ; García‐Gutiérrez, M S ; Manzanares, J ; Leza, J C ; García‐Bueno, B
Assuntos: Animals ; brain frontal cortex ; Cannabinoids - pharmacology ; CB2 receptor ; CB2xP mice ; Chemokine CCL2 - genetics ; Corticosterone - blood ; Cyclooxygenase 2 - metabolism ; Dinoprostone - metabolism ; excitotoxicity ; Frontal Lobe - metabolism ; Glutamic Acid - metabolism ; Inflammation - metabolism ; JWH‐133 ; Male ; Mice, Inbred ICR ; Mice, Transgenic ; neuroinflammation ; NF-kappa B - metabolism ; Nitric Oxide Synthase Type II - metabolism ; Nitrites - metabolism ; Receptor, Cannabinoid, CB2 - agonists ; Receptor, Cannabinoid, CB2 - metabolism ; Research Papers ; stress ; Stress, Psychological - metabolism ; Synaptosomes - metabolism ; Tumor Necrosis Factor-alpha - genetics
É parte de: British journal of pharmacology, 2014-06, Vol.171 (11), p.2814-2826
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: Background and Purpose Stress exposure produces excitotoxicity and neuroinflammation, contributing to the cellular damage observed in stress‐related neuropathologies. The endocannabinoids provide a homeostatic system, present in stress‐responsive neural circuits. Here, we have assessed the possible regulatory role of cannabinoid CB2 receptors in stress‐induced excitotoxicity and neuroinflammation. Experimental Approach We used wild type (WT), transgenic overexpressing CB2 receptors (CB2xP) and CB2 receptor knockout (CB2‐KO) mice exposed to immobilization and acoustic stress (2 h·day−1 for 4 days). The CB2 receptor agonist JWH‐133 was administered daily (2 mg·kg−1, i.p.) to WT and CB2‐KO animals. Glutamate uptake was measured in synaptosomes from frontal cortex; Western blots and RT‐PCR were used to measure proinflammatory cytokines, enzymes and mediators in homogenates of frontal cortex. Key Results Increased plasma corticosterone induced by stress was not modified by manipulating CB2 receptors. JWH‐133 treatment or overexpression of CB2 receptors increased control levels of glutamate uptake, which were reduced by stress back to control levels. JWH‐133 prevented the stress‐induced increase in proinflammatory cytokines (TNF‐α and CCL2), in NF‐κB, and in NOS‐2 and COX‐2 and in the consequent cellular oxidative and nitrosative damage (lipid peroxidation). CB2xP mice exhibited anti‐inflammatory or neuroprotective actions similar to those in JWH‐133 pretreated animals. Conversely, lack of CB2 receptors (CB2‐KO mice) exacerbated stress‐induced neuroinflammatory responses and confirmed that effects of JWH‐133 were mediated through CB2 receptors. Conclusions and Implications Pharmacological manipulation of CB2 receptors is a potential therapeutic strategy for the treatment of stress‐related pathologies with a neuroinflammatory component, such as depression.
Editor: England: Blackwell Publishing Ltd
Idioma: Inglês

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Regulatory role of the cannabinoid CB2 receptor in stress‐induced neuroinflammation in mice

Zoppi, S ; Madrigal, J L ; Caso, J R ; García‐Gutiérrez, M S ; Manzanares, J ; Leza, J C ; García‐Bueno, B

England: Blackwell Publishing Ltd

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