Regulatory role of the cannabinoid CB2 receptor in stress-induced neuroinflammation in mice.
Br J Pharmacol
; 171(11): 2814-26, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24467609
ABSTRACT
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. EXPERIMENTALAPPROACH:
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. KEYRESULTS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse Psicológico
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Receptor CB2 de Canabinoide
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Lobo Frontal
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Inflamação
Limite:
Animals
Idioma:
En
Revista:
Br J Pharmacol
Ano de publicação:
2014
Tipo de documento:
Article