| Autor: |
Doze VA; Department of Pharmacology, Physiology & Therapeutics, School of Medicine & Health Sciences, University of North Dakota, Grand Forks, North Dakota, USA., Papay RS, Goldenstein BL, Gupta MK, Collette KM, Nelson BW, Lyons MJ, Davis BA, Luger EJ, Wood SG, Haselton JR, Simpson PC, Perez DM |
| Jazyk: |
angličtina |
| Zdroj: |
Molecular pharmacology [Mol Pharmacol] 2011 Oct; Vol. 80 (4), pp. 747-58. Date of Electronic Publication: 2011 Jul 26. |
| DOI: |
10.1124/mol.111.073734 |
| Abstrakt: |
The role of α(1)-adrenergic receptors (α(1)ARs) in cognition and mood is controversial, probably as a result of past use of nonselective agents. α(1A)AR activation was recently shown to increase neurogenesis, which is linked to cognition and mood. We studied the effects of long-term α(1A)AR stimulation using transgenic mice engineered to express a constitutively active mutant (CAM) form of the α(1A)AR. CAM-α(1A)AR mice showed enhancements in several behavioral models of learning and memory. In contrast, mice that have the α(1A)AR gene knocked out displayed poor cognitive function. Hippocampal brain slices from CAM-α(1A)AR mice demonstrated increased basal synaptic transmission, paired-pulse facilitation, and long-term potentiation compared with wild-type (WT) mice. WT mice treated with the α(1A)AR-selective agonist cirazoline also showed enhanced cognitive functions. In addition, CAM-α(1A)AR mice exhibited antidepressant and less anxious phenotypes in several behavioral tests compared with WT mice. Furthermore, the lifespan of CAM-α(1A)AR mice was 10% longer than that of WT mice. Our results suggest that long-term α(1A)AR stimulation improves synaptic plasticity, cognitive function, mood, and longevity. This may afford a potential therapeutic target for counteracting the decline in cognitive function and mood associated with aging and neurological disorders. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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