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Title

Aging-related dysregulation of dopamine and angiotensin receptor interaction

AuthorsVillar-Cheda, B.; Dominguez-Meijide, A.; Valenzuela, R.; Granado, Noelia CSIC ORCID; Moratalla, Rosario CSIC ORCID ; Labandeira-García, José L.
KeywordsAging Neuroinflammation Neurodegeneration Oxidative stress Parkinson Renin-angiotensin system Striatum
Issue Date2014
CitationNeurobiology of Aging 35: 1726- 1738 (2014)
AbstractIt is not known whether the aging-related decrease in dopaminergic function leads to the aging-related higher vulnerability of dopaminergic neurons and risk for Parkinson's disease. The renin-angiotensin system (RAS) plays a major role in the inflammatory response, neuronal oxidative stress, and dopaminergic vulnerability via type 1 (AT1) receptors. In the present study, we observed a counterregulatory interaction between dopamine and angiotensin receptors. We observed overexpression of AT1 receptors in the striatum and substantia nigra of young adult dopamine D1 and D2 receptor-deficient mice and young dopamine-depleted rats, together with compensatory overexpression of AT2 receptors or compensatory downregulation of angiotensinogen and/or angiotensin. In aged rats, we observed downregulation of dopamine and dopamine receptors and overexpression of AT1 receptors in aged rats, without compensatory changes observed in young animals. L-Dopa therapy inhibited RAS overactivity in young dopamine-depleted rats, but was ineffective in aged rats. The results suggest that dopamine may play an important role in modulating oxidative stress and inflammation in the substantia nigra and striatum via the RAS, which is impaired by aging. © 2014 Elsevier Inc.
URIhttp://hdl.handle.net/10261/152363
DOIhttp://dx.doi.org/10.1016/j.neurobiolaging.2014.01.017
Identifiersdoi: 10.1016/j.neurobiolaging.2014.01.017
issn: 1558-1497
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