Location of Prorenin Receptors in Primate Substantia Nigra: Effects on Dopaminergic Cell Death

• Published in: Journal of neuropathology and experimental neurology Vol. 69; no. 11; pp. 1130 - 1142
• Main Authors: Valenzuela, Rita, Barroso-Chinea, Pedro, Villar-Cheda, Begoña, Joglar, Belen, Muñoz, Ana, Lanciego, Jose L, Labandeira-Garcia, Jose L
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Association of Neuropathologists, Inc 01.11.2010; Lippincott Williams & Wilkins; Oxford University Press
• Subjects: Adrenergic Agents - toxicity; Animals; Biological and medical sciences; Cell death; Cell Death - physiology; Cells, Cultured; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine - metabolism; Drug Interactions - physiology; Embryo, Mammalian; Glial Fibrillary Acidic Protein - metabolism; Hematologic and hematopoietic diseases; Imidazoles - pharmacology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Macaca fascicularis; Macaca fascicularis - anatomy & histology; Male; Medical sciences; Mesencephalon - cytology; Naphthyridines - pharmacology; Neurology; Neurons - drug effects; Oxidopamine - toxicity; Primates; Pyridines - pharmacology; Rats; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Renin - pharmacology; Substantia Nigra - metabolism; Tyrosine 3-Monooxygenase - metabolism; Vacuolar Proton-Translocating ATPases - metabolism; Neuroglia; Central nervous system; Monkey; Parkinson disease; Neuro-degeneration; Encephalon; Renin; Primates; Aspartic endopeptidases; Degenerative disease; Degeneration; Biological receptor; Nervous system diseases; Dopamine; Enzyme; Catecholamine; Cerebral disorder; Microglia; Peptidases; Renin angiotensin system; Vertebrata; Mammalia; Locus niger; Cell death; Animal; Central nervous system disease; Angiotensin; Neurotransmitter; Hydrolases; Extrapyramidal syndrome
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1097/NEN.0b013e3181fa0308

Angiotensin II acts via angiotensin type 1 receptors and is a major inducer of inflammation and oxidative stress. Local renin-angiotensin systems play a major role in the development of age-related disorders in several tissues. These processes are delayed, but not totally abolished, by blockade of angiotensin signaling. A specific receptor for renin and its precursor prorenin has recently been identified. We previously showed that neurotoxin-induced dopaminergic (DA) cell loss is decreased by inhibition of angiotensin receptors, but the location and functional effects of prorenin receptor (PRR) in the brain, including theDA system, are unknown. In the substantia nigra of Macaca fascicularis and in rat primary mesencephalic cultures, double immunofluorescence analysis revealed PRR immunoreactivity in neurons (including DA neurons) and microglia, but not in astrocytes. Administration of the PRR blocker, handle region peptide, led to a significant decrease in 6-hydroxydopamine-induced DA cell death in the cultures,whereas administration of renin with simultaneous blockade ofangiotensin receptors led to an increase in 6-hydroxydopamine-induced cell death. These results suggest that active agent angiotensin II-independent PRR intracellular signaling may contribute to exacerbation of DA cell death in vivo. Therefore, potential neuroprotective strategies for DA neurons in Parkinson disease should address both angiotensin and PRR signaling.