RT Journal Article
T1 Renin angiotensin system and gender differences in dopaminergic degeneration
A1 Rodríguez Pérez, Ana Isabel
A1 Valenzuela Limiñana, Rita
A1 Joglar, Belén
A1 Garrido Gil, Pablo
A1 Guerra Seijas, María Josefa Natividad
A1 Labandeira García, José Luis
K1 Angiotensin
K1 Estrogen
K1 Menopause
K1 NADPH-oxidase complex
K1 Neurodegeneration
K1 Oxidative stress
K1 Parkinson
K1 Sex differences
AB Background: There are sex differences in dopaminergic degeneration. Men are approximately two times as likelyas premenopausal women of the same age to develop Parkinson’s disease (PD). It has been shown that the localrenin angiotensin system (RAS) plays a prominent role in sex differences in the development of chronic renal andcardiovascular diseases, and there is a local RAS in the substantia nigra and dopaminergic cell loss is enhanced byangiotensin via type 1 (AT1) receptors.Results: In the present study, we observed that intrastriatal injection of 6-hydroxydopamine induced a marked lossof dopaminergic neurons in the substantia nigra of male rats, which was significantly higher than the loss inducedin ovariectomized female rats given estrogen implants (i.e. rats with estrogen). However, the loss of dopaminergicneurons was significantly lower in male rats treated with the AT1 antagonist candesartan, and similar to thatobserved in female rats with estrogen. The involvement of the RAS in gender differences in dopaminergicdegeneration was confirmed with AT1a-null mice lesioned with the dopaminergic neurotoxin MPTP. Significantlyhigher 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.
PB BMC
YR 2011
FD 2011
LK http://hdl.handle.net/10347/21634
UL http://hdl.handle.net/10347/21634
LA eng
NO Rodriguez-Perez, A.I., Valenzuela, R., Joglar, B. et al. Renin angiotensin system and gender differences in dopaminergic degeneration. "Mol Neurodegeneration" 6, 58 (2011)
NO Funding: Spanish Ministry of Science and Innovation, Spanish Ministry of Health (RD06/0010/0013 and CIBERNED), Galician Government (XUGA) and FEDER
DS Minerva
RD 24 abr 2026