RT Journal Article
T1 Imbalance of Endocannabinoid/Lysophosphatidylinositol Receptors Marks the Severity of Alzheimer's Disease in a Preclinical Model: A Therapeutic Opportunity.
A1 Medina-Vera, Dina
A1 Rosell-Valle, Cristina
A1 López-Gambero, Antonio J
A1 Navarro, Juan A
A1 Zambrana-Infantes, Emma N
A1 Rivera, Patricia
A1 Santín, Luis J
A1 Suarez, Juan
A1 Rodríguez de Fonseca, Fernando
K1 5xFAD
K1 Alzheimer’s disease
K1 GPR55
K1 amyloid-β
K1 endocannabinoid system
K1 neuroinflammation
AB Alzheimer's disease (AD) is the most common form of neurodegeneration and dementia. The endocannabinoid (ECB) system has been proposed as a novel therapeutic target to treat AD. The present study explores the expression of the ECB system, the ECB-related receptor GPR55, and cognitive functions (novel object recognition; NOR) in the 5xFAD (FAD: family Alzheimer's disease) transgenic mouse model of AD. Experiments were performed on heterozygous (HTZ) and homozygous (HZ) 11 month old mice. Protein expression of ECB system components, neuroinflammation markers, and β-amyloid (Aβ) plaques were analyzed in the hippocampus. According to the NOR test, anxiety-like behavior and memory were altered in both HTZ and HZ 5xFAD mice. Furthermore, both animal groups displayed a reduction of cannabinoid (CB1) receptor expression in the hippocampus, which is related to memory dysfunction. This finding was associated with indirect markers of enhanced ECB production, resulting from the combination of impaired monoacylglycerol lipase (MAGL) degradation and increased diacylglycerol lipase (DAGL) levels, an effect observed in the HZ group. Regarding neuroinflammation, we observed increased levels of CB2 receptors in the HZ group that positively correlate with Aβ's accumulation. Moreover, HZ 5xFAD mice also exhibited increased expression of the GPR55 receptor. These results highlight the importance of the ECB signaling for the AD pathogenesis development beyond Aβ deposition.
SN 2079-7737
YR 2020
FD 2020-11-05
LK https://hdl.handle.net/10668/28404
UL https://hdl.handle.net/10668/28404
LA en
DS RISalud
RD Apr 11, 2025