VMAT2 and dopamine neuron loss in a primate model of Parkinson's disease.

VMAT2 and dopamine neuron loss in a primate model of Parkinson's disease. Research Abstract Details 

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VMAT2 and dopamine neuron loss in a primate model of Parkinson's disease. Abstract Text:

Ming-Kai Chen,Hiroto Kuwabara,Yun Zhou,Robert J Adams,James R Brasi?,Jennifer L McGlothan,Tatyana Verina,Neal C Burton,Mohab Alexander,Anil Kumar,Dean F Wong, Guilarte,

We used positron emission tomography (PET) to measure the earliest change in dopaminergic synapses and glial cell markers in a chronic, low-dose MPTP non-human primate model of Parkinson's disease (PD). In vivo levels of dopamine transporters (DAT), vesicular monoamine transporter-type 2 (VMAT2), amphetamine-induced dopamine release (AMPH-DAR), D2-dopamine receptors (D2R) and translocator protein 18 kDa (TSPO) were measured longitudinally in the striatum of MPTP-treated animals. We report an early (2 months) decrease (46%) of striatal VMAT2 in asymptomatic MPTP animals that preceded changes in DAT, D2R, and AMPH-DAR and was associated with increased TSPO levels indicative of a glial response. Subsequent PET studies showed progressive loss of all pre-synaptic dopamine markers in the striatum with expression of parkinsonism. However, glial cell activation did not track disease progression. These findings indicate that decreased VMAT2 is a key pathogenic event that precedes nigrostriatal dopamine neuron degeneration. The loss of VMAT2 may result from an association with alpha-synuclein aggregation induced by oxidative stress. Disruption of dopamine sequestration by reducing VMAT2 is an early pathogenic event in the dopamine neuron degeneration that occurs in the MPTP non-human primate model of PD. Genetic or environmental factors that decrease VMAT2 function may be important determinants of PD.

VMAT2 and dopamine neuron loss in a primate model of Parkinson's disease. Publishing Authors By Initials

MK Chen,H Kuwabara,Y Zhou,RJ Adams,JR Brasi?,JL McGlothan,T Verina,NC Burton,M Alexander,A Kumar,DF Wong,TR Guilarte,

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VMAT2 and dopamine neuron loss in a primate model of Parkinson's disease. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of neurochemistry

VOLUME: 105

Page Numbers: 78-90

Journal Abbreviation: J. Neurochem.

ISSN: 1471-4159

DAY: 5

MONTH: 11

YEAR: 2007

VMAT2 and dopamine neuron loss in a primate model of Parkinson's disease. Information

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LANGUAGE: eng

NlmUniqueID: 2985190

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Grant and Affiliation Information for VMAT2 and dopamine neuron loss in a primate model of Parkinson's disease.

AFFILIATION: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.

Country: England

AGENCY: United States NIEHS

GRANT: ES07062

ACRONYM: ES

MEDLINETA: J Neurochem

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