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Effects of sildenafil on nigrostriatal dopamine neurons in a murine model of Parkinson's disease. J Alzheimers Dis 2008 Sep;15(1):97-107



Pubmed ID





The objective of this study was to determine if the phosphodiesterase 5 (PDE-5) inhibitor, sildenafil, could be used as a neuroprotective agent in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) murine model of Parkinson's disease. The underlying hypothesis of these studies is that blockade of PDE-5 catabolism of cGMP will attenuate the loss of nigrostriatal dopamine (NSDA) neurons following chronic neurotoxin exposure. Chronic MPTP-treated mice were administered sildenafil using three different regimens. Animals were: 1) treated with sildenafil and then exposed to chronic MPTP; 2) treated concurrently with sildenafil and MPTP; and 3) first exposed to MPTP and subsequently treated with sildenafil. End points of neurotoxicity included dopamine (DA) and tyrosine hydroxylase (TH) concentrations in NSDA axon terminals in the striatum, and stereological cell counts of TH immunoreactive neurons in the substantia nigra. Results reveal that sildenafil did not prevent neurotoxicity produced by chronic MPTP exposure regardless of the treatment paradigms employed. On the other hand, sildenafil did not produce any deleterious effect on NSDA neuron function nor did it potentiate the neurotoxic effects of MPTP. These results suggest that sildenafil would not accelerate DA cell loss when used as a treatment for erectile dysfunction in men diagnosed with Parkinson's disease.

Author List

Janis KL, Brennan RT, Drolet RE, Behrouz B, Kaufman SK, Lookingland KJ, Goudreau JL


Ryan T. Brennan DO Assistant Professor in the Neurology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Blotting, Western
Corpus Striatum
Cyclic GMP-Dependent Protein Kinases
Disease Models, Animal
Mice, Inbred C57BL
Parkinsonian Disorders
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Sildenafil Citrate
Substantia Nigra
Tyrosine 3-Monooxygenase
jenkins-FCD Prod-480 9a4deaf152b0b06dd18151814fff2e18f6c05280