Renin angiotensin system and gender differences in dopaminergic degeneration

Molecular Neurodegeneration

Jose L Labandeira-Garcia¹  Maria J Guerra¹  Pablo Garrido-Gil¹  Belen Joglar¹  Rita Valenzuela¹  Ana I Rodriguez-Perez¹ 

[1] Department of Morphological Sciences, Networking Research Center on Neurodegenerative Diseases (CIBERNED), University of Santiago de Compostela, Santiago de Compostela, E-15782 Spain

关键词: sex differences;    Parkinson;    oxidative stress;    neurodegeneration;    NADPH-oxidase complex;    menopause;    estrogen;    angiotensin;   

Others  :  865694
DOI  :  10.1186/1750-1326-6-58

 received in 2011-04-07, accepted in 2011-08-16,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Rodriguez-Perez et al; licensee BioMed Central Ltd.

【 图 表 】

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