Imbalance of Endocannabinoid/Lysophosphatidylinositol Receptors Marks the Severity of Alzheimer's Disease in a Preclinical Model: A Therapeutic Opportunity
| Autor: | Antonio J. López-Gambero, Fernando Rodríguez de Fonseca, Juan Antonio Navarro, Dina Medina-Vera, Emma Zambrana-Infantes, Cristina Rosell-Valle, Patricia Rivera, Juan Suárez, Luis J. Santín |
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| Přispěvatelé: | [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., This work was supported by grants from the following institutions: European Regional Development Funds-European Union (ERDF-EU) Fondos FEDER 'una manera de hacer Europa,' and Fatzheimer project EULAC-HEALTH H2020 (EULACH16/T010131). Ministerio de Economía y Competitividad, Gobierno de España (Grant RTC-2016-4983-1), EU-ERDF-Instituto de Salud Carlos III (Grant PI19/01577 and PI19/00343), and Consejería de Economía, Conocimiento y Universidad, Junta de Andalucía (Grant P18-TP-5194). J.S. (CPII17/00024) holds a ‘’Miguel Servet II' research contract from the National System of Health, EU-ERDF-Instituto de Salud Carlos III. P.R. (CP19/00068) holds a ‘’Miguel Servet I' research contract from the National System of Health, EU-ERDF-Instituto de Salud Carlos III. D.M-V. (FI20/00227) holds a ‘’PFIS' predoctoral contract from the National System of Health, EU-ERDF-Instituto de Salud Carlos III. A.J.L.-G. (IFI18/00042) holds an 'iPFIS' predoctoral contract from the National System of Health, EU-ERDF-Instituto de Salud Carlos III. |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Diacylglycerol lipase Cannabinoid receptor Endocannabinoid system Receptor expression amyloid-β General Biochemistry Genetics and Molecular Biology Article neuroinflammation Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Membrane Proteins::Receptors Cell Surface::Receptors G-Protein-Coupled::Receptors Cannabinoid::Receptor Cannabinoid CB1 [Medical Subject Headings] Neuroinflammation Péptidos beta-amiloides Internal medicine Enfermedad de Alzheimer medicine Cannabinoid receptor type 2 Organisms::Eukaryota::Animals [Medical Subject Headings] Amyloid-β Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Dementia::Alzheimer Disease [Medical Subject Headings] Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hippocampus [Medical Subject Headings] Chemicals and Drugs::Lipids::Fatty Acids::Endocannabinoids [Medical Subject Headings] endocannabinoid system lcsh:QH301-705.5 Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings] Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Cognition [Medical Subject Headings] General Immunology and Microbiology biology Enfermedades neuroinflamatorias Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds 2-Ring::Pteridines::Flavins::Riboflavin::Flavin-Adenine Dinucleotide [Medical Subject Headings] Neurodegeneration medicine.disease Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Membrane Proteins::Receptors Cell Surface::Receptors G-Protein-Coupled::Receptors Cannabinoid::Receptor Cannabinoid CB2 [Medical Subject Headings] 5xFAD Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Carboxylic Ester Hydrolases::Monoacylglycerol Lipases [Medical Subject Headings] Monoacylglycerol lipase Endocannabinoides Endocrinology lcsh:Biology (General) GPR55 biology.protein Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Carboxylic Ester Hydrolases::Lipoprotein Lipase [Medical Subject Headings] Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice Transgenic [Medical Subject Headings] General Agricultural and Biological Sciences Alzheimer’s disease Psychiatry and Psychology::Behavior and Behavior Mechanisms::Emotions::Anxiety::Performance Anxiety [Medical Subject Headings] Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Terpenes::Cannabinoids [Medical Subject Headings] |
| Zdroj: | Biology Volume 9 Issue 11 Biology, Vol 9, Iss 377, p 377 (2020) |
| Popis: | Alzheimer&rsquo 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&rsquo 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 &beta amyloid (A&beta ) 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 A&beta &rsquo 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 A&beta deposition. |
| Databáze: | OpenAIRE |
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