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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Poppensieker, Karola Alferink, Judith Piyanova, Anastasia Zimmer, Andreas Bilkei-gorzo, Andras Pitsch, Julika Mauer, Daniela Neitzert, Kim Monory, Krisztina Legler, Anne Lutz, Beat Michel, Kerstin Albayram, Onder Becker, Albert |
| Description | Author Affiliation: Albayram O ( Institute of Molecular Psychiatry, University of Bonn, 53127 Bonn, Germany.); |
| Abstract | Brain aging is associated with cognitive decline that is accompanied by progressive neuroinflammatory changes. The endocannabinoid system (ECS) is involved in the regulation of glial activity and influences the progression of age-related learning and memory deficits. Mice lacking the Cnr1 gene (Cnr1(-/-)), which encodes the cannabinoid receptor 1 (CB1), showed an accelerated age-dependent deficit in spatial learning accompanied by a loss of principal neurons in the hippocampus. The age-dependent decrease in neuronal numbers in Cnr1(-/-) mice was not related to decreased neurogenesis or to epileptic seizures. However, enhanced neuroinflammation characterized by an increased density of astrocytes and activated microglia as well as an enhanced expression of the inflammatory cytokine IL-6 during aging was present in the hippocampus of Cnr1(-/-) mice. The ongoing process of pyramidal cell degeneration and neuroinflammation can exacerbate each other and both contribute to the cognitive deficits. Deletion of CB1 receptors from the forebrain GABAergic, but not from the glutamatergic neurons, led to a similar neuronal loss and increased neuroinflammation in the hippocampus as observed in animals lacking CB1 receptors in all cells. Our results suggest that CB1 receptor activity on hippocampal GABAergic neurons protects against age-dependent cognitive decline by reducing pyramidal cell degeneration and neuroinflammation. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 27 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Aging Physiology Brain Receptor, Cannabinoid, CB1 Animals Cytology Cell Count Gene Expression Hippocampus Interleukin-6 Genetics Maze Learning Memory Mice Mice, Inbred C57BL Mice, Knockout Neurogenesis Neuroglia Neurons Deficiency Seizures Pathology Physiopathology Gamma-Aminobutyric Acid Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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