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Molecular Neurodegeneration

, 6:58

First Online: 16 August 2011Received: 07 April 2011Accepted: 16 August 2011

Abstract

BackgroundThere 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.

ResultsIn 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.

ConclusionsThe 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.

Keywordsangiotensin estrogen menopause NADPH-oxidase complex neurodegeneration oxidative stress Parkinson sex differences List of abbreviations6-OHDA6-hydroxydopamine

ACEAngiotensin converting enzyme

AIIAngiotensin II

AT1Angiotensin type 1 receptors

AT1AT1a-null mice

AT2Angiotensin receptors type 2

DADopaminergic

E2Estrogen

MPTP1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

ovxOvariectomized

PDParkinson-s disease

RASRenin angiotensin system

ROSReactive oxygen species

TH-irTyrosine hydroxylase immunoreactive

WBWestern Blot

WTwild type mice.

Electronic supplementary materialThe online version of this article doi:10.1186-1750-1326-6-58 contains supplementary material, which is available to authorized users.

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Author: Ana I Rodriguez-Perez - Rita Valenzuela - Belen Joglar - Pablo Garrido-Gil - Maria J Guerra - Jose L Labandeira-Garcia

Source: https://link.springer.com/







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