Altered expression of the CB1 cannabinoid receptor in the triple transgenic mouse model of Alzheimer's disease
| Autor: | Gaurav Bedse, Tommaso Cassano, Caterina Grillo, Gianluigi Vendemiale, Pace Lorenzo, Angelo Michele Lavecchia, Maurice R. Elphick, Silvia Cianci, Adele Romano, Silvana Gaetani, Frank M. LaFerla, Fabio Altieri |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Cannabinoid receptor Infralimbic cortex Hippocampus Mice Transgenic tau Proteins Neuropathology Biology Amyloid beta-Protein Precursor Mice Receptor Cannabinoid CB1 Alzheimer Disease Internal medicine 3×tg-ad mice alzheimer’s disease endocannabinoid system basolateral amygdala complex alzheimer's disease 3 × tg-ad mice hippocampus prefrontal cortex cb1 receptor 3xtg-ad mice cb1 mrna prefrontal corte medicine Presenilin-1 Animals Humans RNA Messenger Prefrontal cortex Cerebral Cortex Analysis of Variance musculoskeletal neural and ocular physiology General Neuroscience Age Factors General Medicine Endocannabinoid system Psychiatry and Mental health Clinical Psychology Disease Models Animal medicine.anatomical_structure Endocrinology nervous system Gene Expression Regulation Cerebral cortex Mutation lipids (amino acids peptides and proteins) Geriatrics and Gerontology psychological phenomena and processes Basolateral amygdala |
| Zdroj: | Journal of Alzheimer's disease : JAD. 40(3) |
| ISSN: | 1875-8908 |
| Popis: | The endocannabinoid system has gained much attention as a new potential pharmacotherapeutic target in various neurodegenerative diseases, including Alzheimer's disease (AD). However, the association between CB1 alterations and the development of AD neuropathology is unclear and often contradictory. In this study, brain CB1 mRNA and CB1 protein levels were analyzed in 3 × Tg-AD mice and compared to wild-type littermates at 2, 6 and 12 months of age, using in-situ hybridization and immunohistochemistry, respectively. Semiquantitative analysis of CB1 expression focused on the prefrontal cortex (PFC), prelimbic cortex, dorsal hippocampus (DH), basolateral amygdala complex (BLA), and ventral hippocampus (VH), all areas with high CB1 densities that are strongly affected by neuropathology in 3 × Tg-AD mice. At 2 months of age, there was no change in CB1 mRNA and protein levels in 3 × Tg-AD mice compared to Non-Tg mice in all brain areas analyzed. However, at 6 and 12 months of age, CB1 mRNA levels were significantly higher in PFC, DH, and BLA, and lower in VH in 3 × Tg-AD mice compared to wild-type littermates. CB1 immunohistochemistry revealed that CB1 protein expression was unchanged in 3 × Tg-AD at 2 and 6 months of age, while a significant decrease in CB1 receptor immunoreactivity was detected in the BLA and DH of 12-month-old 3 × Tg-AD mice, with no sign of alteration in other brain areas. The altered CB1 levels appear, rather, to be age-and/or pathology-dependent, indicating an involvement of the endocannabinoid system in AD pathology and supporting the ECS as a potential novel therapeutic target for treatment of AD. |
| Databáze: | OpenAIRE |
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