Cannabinoid Receptor 2-Deficiency Ameliorates Disease Symptoms in a Mouse Model with Alzheimer's Disease-Like Pathology.
J Alzheimers Dis
; 64(2): 379-392, 2018.
Article
de En
| MEDLINE
| ID: mdl-29865078
ABSTRACT
It is widely accepted that the endocannabinoid system (ECS) is a modulator of neuroinflammation associated with neurodegenerative disorders, including Alzheimer's disease (AD). Thus, expression of the cannabinoid receptor 2 (CB2) is induced in plaque-associated microglia and astrocytes in brain tissues from AD patients and in genetic mouse models expressing pathogenic variants of the amyloid precursor protein (APP). However, the exact mechanism of CB2 signaling in this mouse model remains elusive, because the genetic deletion of CB2 and the pharmacological activation of CB2 both reduced neuroinflammation. Here, we demonstrate that CB2 deletion also improved cognitive and learning deficits in APP/PS1*CB2-/- mice. This was accompanied by reduced neuronal loss and decreased plaque levels and coincided with increased expression of Aß degrading enzymes. Interestingly, plaque-associated microglia in APP/PS1*CB2-/- mice showed a less activated morphology, while plaques were smaller and more condensed than in APP/PS1 mice. Taken together, these results indicate a beneficial effect of CB2-deficiency in APP transgenic mice. CB2 appears to be part of a protective system that may be detrimental when engaged continuously.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Régulation de l'expression des gènes
/
Plaque amyloïde
/
Récepteur cannabinoïde de type CB2
/
Maladie d'Alzheimer
Type d'étude:
Diagnostic_studies
/
Prognostic_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
J Alzheimers Dis
Sujet du journal:
GERIATRIA
/
NEUROLOGIA
Année:
2018
Type de document:
Article
Pays d'affiliation:
Allemagne