Medina-Vera, DinaRosell-Valle, CristinaLópez-Gambero, Antonio J.Navarro, Juan A.Zambrana-Infantes, Emma N.Rivera, PatriciaSantín, Luis J.Suarez, JuanRodríguez de Fonseca, Fernando2022-07-082022-07-082020-11-05Medina-Vera D, Rosell-Valle C, López-Gambero AJ, Navarro JA, Zambrana-Infantes EN, Rivera P, et al. Imbalance of Endocannabinoid/Lysophosphatidylinositol Receptors Marks the Severity of Alzheimer's Disease in a Preclinical Model: A Therapeutic Opportunity. Biology. 2020 Nov 5;9(11):377http://hdl.handle.net/10668/3770Alzheimer'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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Alzheimer’s disease5xFADEndocannabinoid systemAmyloid-βNeuroinflammationGPR55Enfermedad de AlzheimerEnfermedades neuroinflamatoriasPéptidos beta-amiloidesEndocannabinoidesMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Dementia::Alzheimer DiseaseMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Carboxylic Ester Hydrolases::Monoacylglycerol LipasesMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::EndocannabinoidsMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Pteridines::Flavins::Riboflavin::Flavin-Adenine DinucleotideMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Carboxylic Ester Hydrolases::Lipoprotein LipaseMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB2Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB1Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Emotions::Anxiety::Performance AnxietyMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, TransgenicMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::HippocampusMedical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::CognitionMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Terpenes::Cannabinoidsresearch article33167441open access10.3390/biology91103772079-7737PMC7694492