Faculty Collaboration Database

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

Date

09/11/2008

Pubmed ID

18780970

DOI

10.3233/jad-2008-15108

Scopus ID

2-s2.0-52449093691 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

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

Author

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

Animals
Axons
Blotting, Western
Corpus Striatum
Cyclic GMP-Dependent Protein Kinases
Disease Models, Animal
Dopamine
Mice
Mice, Inbred C57BL
Neurons
Parkinsonian Disorders
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Piperazines
Purines
Sildenafil Citrate
Substantia Nigra
Sulfones
Tyrosine 3-Monooxygenase