2026-07-21T07:35:44Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/181482024-11-28T15:37:10Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud
author
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
authoraffiliation
[Medina-Vera,D; Rosell-Valle,C; López-Gambero,AJ; Navarro,JA; Rivera,P; Suarez,J; Rodríguez de Fonseca,F] Instituto de Investigación Biomédica de Málaga-IBIMA, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Málaga, Spain. [Medina-Vera,D; López-Gambero,AJ] Facultad de Ciencias, Universidad de Málaga, Málaga, Spain. [Medina-Vera,D; Navarro,JA] Facultad de Medicina, Universidad de Málaga, Málaga, Spain. [Zambrana-Infantes,EN; Santín,LJ] Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain.
2024-02-12T19:47:51Z
2024-02-12T19:47:51Z
2020-11-05
10.3390/biology9110377
2079-7737
Biology
http://hdl.handle.net/10668/3770
33167441
http://hdl.handle.net/20.500.12105/18148
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.
eng
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
research article