Detalle Publicación


Dopaminergic degeneration is enhanced by chronic brain hypoperfusion and inhibited by angiotensin receptor blockage

Autores: Rodríguez-Pérez, A. I.; Dominguez-Meijide, A.; Lanciego Pérez, José Luis; Guerra, M. J.; Labandeira-Garcia, J. L.
Título de la revista: AGE
ISSN: 0161-9152
Volumen: 35
Número: 5
Páginas: 1675 - 1690
Fecha de publicación: 2013
The possible interaction between brain hypoperfusion related to aging and/or vascular disease, vascular parkinsonism and Parkinson's disease, as well as the possible contribution of aging-related chronic brain hypoperfusion in the development or severity of Parkinson's disease are largely unknown. We used a rat model of chronic cerebral hypoperfusion to study the long-term effects of hypoperfusion on dopaminergic neurons and the possible synergistic effects between chronic hypoperfusion and factors that are deleterious to dopaminergic neurons, such as the dopaminergic neurotoxin 6-hydroxydopamine. Chronic hypoperfusion induced significant loss of dopaminergic neurons and striatal dopaminergic terminals and a reduction in striatal dopamine levels. Furthermore, intrastriatal administration of 6-hydroxydopamine in rats subjected to chronic hypoperfusion induced a significantly greater loss of dopaminergic neurons than in sham-operated control rats. The dopaminergic neuron loss was significantly reduced by oral treatment with angiotensin type 1 receptor antagonist candesartan (3 mg/kg/day). The levels of angiotensin type 2 receptors were lower and the levels of angiotensin type 1 receptors, interleukin-1 beta and nicotinamide adenine dinucleotide phosphate oxidase activity were higher in the substantia nigra of rats subjected to chronic hypoperfusion than in control rats; this was significantly reduced by treatment with candesartan. The results suggest that early treatment of vascular disease should be considered in the treatment of aged Parkinson's disease patients and Parkinson's disease patients with cerebrovascular risk factors. The findings also suggest that inhibition of brain renin-angiotensin activity may be useful as a neuroprotective strategy.