Parkinson-like Degenerative Changes Linked to Reduced Dopamine Storage

W. Michael Caudle, Jason R. Richardson, Ph.D., Gary W. Miller, Ph.D.
Emory University and Donato DiMonte, MD, The Parkinson’s Institute
T32ES12870, F32ES013457, R21ES013828, U54ES012068, R01ES010806, and U54ES012077

Mice with a decreased ability to package and store dopamine undergo a degenerative process that mimics Parkinson’s disease report NIEHS-supported neuroscientists at Emory University in Atlanta and The Parkinson’s Institute in Sunnyvale, Ca. Mice genetically altered to produce only five percent of the normal levels of a protein called vesicular monoamine transporter 2 (VMAT2) were used in the experiment. VMAT2 is responsible for packaging dopamine for future release by neurons.

Lack of the neurotransmitter dopamine is responsible for many of the symptoms related to Parkinson’s disease, a progressive neurodegenerative disease that strikes Americans at the rate of about 20/100,000 per year. Estimates of the current number of Parkinson’s cases in the U.S. vary between 300,000 and 750,000. Current treatments include administration of the dopamine precursor, L-dopa.

The mice, known as VMAT2 LO, were carefully bred so that they were only deficient in the VMAT2 gene. Previous research found that this mouse strain included a chromosomal deletion spanning the a-synuclein gene locus. The mice used in the current study were screened to verify the presence of a-synuclein; this study represents the first data on VMAT2 LO mice with normal a-synuclein expression. The investigators will continue this line of research using these mice to test compounds that can possibly slow the course of the Parkinson symptoms.

Citation: Caudle WM, Richardson JR, Wang MZ, Taylor TN, Guillot TS, McCormack AL, Colebrooke RE, Di Monte DA, Emson PC, Miller GW. Reduced vesicular storage of dopamine causes progressive nigrostriatal neurodegeneration. J Neurosci. 2007 Jul 25;27(30):8138-48.