title: Aging-related dysregulation of dopamine and angiotensin receptor interaction.
abstract: It 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.
authors: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain; Networking Research Centre on Neurodegenerative Diseases (CIBERNED), Spain.
authors: Begoña
authors: B
authors: Villar-Cheda
authors: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain; Networking Research Centre on Neurodegenerative Diseases (CIBERNED), Spain.
authors: Antonio
authors: A
authors: Dominguez-Meijide
authors: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain; Networking Research Centre on Neurodegenerative Diseases (CIBERNED), Spain.
authors: Rita
authors: R
authors: Valenzuela
authors: Networking Research Centre on Neurodegenerative Diseases (CIBERNED), Spain; Instituto Cajal CSIC (Consejo Superior de Investigaciones Científicas), Madrid, Spain.
authors: Noelia
authors: N
authors: Granado
authors: Networking Research Centre on Neurodegenerative Diseases (CIBERNED), Spain; Instituto Cajal CSIC (Consejo Superior de Investigaciones Científicas), Madrid, Spain.
authors: Rosario
authors: R
authors: Moratalla
authors: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain; Networking Research Centre on Neurodegenerative Diseases (CIBERNED), Spain. Electronic address: joseluis.labandeira@usc.es.
authors: Jose L
authors: JL
authors: Labandeira-Garcia
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000502:physiology; D015536:Down-Regulation; D015870:Gene Expression; D007249:Inflammation / Q000235:genetics; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D012306:Risk; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology
chemical_list: D044140:Receptor, Angiotensin, Type 1; D011954:Receptors, Dopamine; D004298:Dopamine
keywords: Aging; Neurodegeneration; Neuroinflammation; Oxidative stress; Parkinson; Renin-angiotensin system; Striatum