Renin angiotensin system and gender differences in dopaminergic degeneration
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Title: | Renin angiotensin system and gender differences in dopaminergic degeneration |
Author: | Rodríguez Pérez, Ana Isabel Valenzuela Limiñana, Rita Joglar, Belén Garrido Gil, Pablo Guerra Seijas, María Josefa Natividad Labandeira García, José Luis |
Affiliation: | Universidade de Santiago de Compostela. Departamento de Ciencias Morfolóxicas |
Subject: | Angiotensin | Estrogen | Menopause | NADPH-oxidase complex | Neurodegeneration | Oxidative stress | Parkinson | Sex differences | |
Date of Issue: | 2011 |
Publisher: | BMC |
Citation: | Rodriguez-Perez, A.I., Valenzuela, R., Joglar, B. et al. Renin angiotensin system and gender differences in dopaminergic degeneration. "Mol Neurodegeneration" 6, 58 (2011) |
Abstract: | Background: There are sex differences in dopaminergic degeneration. Men are approximately two times as likely as premenopausal women of the same age to develop Parkinson’s disease (PD). It has been shown that the local renin angiotensin system (RAS) plays a prominent role in sex differences in the development of chronic renal and cardiovascular diseases, and there is a local RAS in the substantia nigra and dopaminergic cell loss is enhanced by angiotensin via type 1 (AT1) receptors. Results: In the present study, we observed that intrastriatal injection of 6-hydroxydopamine induced a marked loss of dopaminergic neurons in the substantia nigra of male rats, which was significantly higher than the loss induced in ovariectomized female rats given estrogen implants (i.e. rats with estrogen). However, the loss of dopaminergic neurons was significantly lower in male rats treated with the AT1 antagonist candesartan, and similar to that observed in female rats with estrogen. The involvement of the RAS in gender differences in dopaminergic degeneration was confirmed with AT1a-null mice lesioned with the dopaminergic neurotoxin MPTP. Significantly higher expression of AT1 receptors, angiotensin converting enzyme activity, and NADPH-oxidase complex activity, and much lower levels of AT2 receptors were observed in male rats than in female rats with estrogen. Conclusions: The results suggest that brain RAS plays a major role in the increased risk of developing PD in men, and that manipulation of brain RAS may be an efficient approach for neuroprotective treatment of PD in men, without the feminizing effects of estrogen. |
Publisher version: | https://doi.org/10.1186/1750-1326-6-58 |
URI: | http://hdl.handle.net/10347/21634 |
DOI: | 10.1186/1750-1326-6-58 |
E-ISSN: | 1750-1326 |
Rights: | © 2011 Rodriguez-Perez et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited |
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Except where otherwise noted, this item's license is described as © 2011 Rodriguez-Perez et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited