2026-07-21T07:35:44Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/181482024-11-28T15:37:10Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc Medina-Vera, Dina author Rosell-Valle, Cristina author López-Gambero, Antonio J. author Navarro, Juan A. author Zambrana-Infantes, Emma N. author Rivera, Patricia author Santín, Luis J. author Suarez, Juan author Rodríguez de Fonseca, Fernando author 2020-11-05 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. 10.3390/biology9110377 2079-7737 Biology http://hdl.handle.net/10668/3770 33167441 http://hdl.handle.net/20.500.12105/18148 Alzheimer’s disease 5xFAD Endocannabinoid system Amyloid-β Neuroinflammation GPR55 Enfermedad de Alzheimer Enfermedades neuroinflamatorias Péptidos beta-amiloides Endocannabinoides Imbalance of Endocannabinoid/Lysophosphatidylinositol Receptors Marks the Severity of Alzheimer's Disease in a Preclinical Model: A Therapeutic Opportunity