Vesicular monoamine transporter 2 mRNA levels are reduced in platelets from patients with Parkinson’s disease

Abstract

Despite advances in neuroimaging, the diagnosis of idiopathic Parkinson's disease (PD) remains clinical. The identification of biological markers for an early diagnosis is of great interest to start a neuroprotective therapy aimed at slowing, blocking or reversing the disease progression. Vesicular monoamine transporter 2 (VMAT2) sequesters cytoplasmic dopamine into synaptic vesicles for storage and release. Thus, VMAT2 impairment can regulate intra- and extracellular dopamine levels, influencing oxidative stress and neuronal death. Because in vivo imaging studies have demonstrated a VMAT2 reduction in PD patients greater than would be explained by neuronal loss alone, as an exploratory study we assessed VMAT2 mRNA and protein levels in platelets from 39 PD patients, 39 healthy subjects and 10 patients with vascular parkinsonism (VP) to identify a possible peripheral biomarker for PD. A significant reduction (p < 0.05) of VMAT2 mRNA levels was demonstrated in PD patients versus healthy controls. Patients with VP showed VMAT2 mRNA levels similar to controls. No difference in VMAT2 mRNA levels was found in untreated versus treated patients. No correlation was observed between mRNA levels and demographic or clinical characteristics. Furthermore, eight SNPs tagging the VMAT2 gene did not show effects on VMAT2 mRNA levels. Western blot analysis did not allow the quantification of VMAT2 protein expression in blood platelets. Although further studies in a greater number of cases are needed to confirm our data, the reduction in VMAT2 mRNA in platelets from PD patients suggests the existence of a systemic impairment of this transporter possibly contributing to PD pathology.

Ginkgo biloba extract (EGb 761) modulates the expression of dopamine-related genes in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice

“…A reduction in VMAT2 expression has been reported in PD patients (Frey et al, 2001). Furthermore, Vmat2 mRNA levels were found to be reduced in the platelets (Sala et al, 2010) and substantia nigra of PD patients (Harrington et al, 1996). These findings suggest the existence of an impairment of this transporter that could contribute to PD pathology (Sala et al, 2010).…”

Intra-neuronal vesicular uptake of catecholamines is decreased in patients with Lewy body diseases

“…A recent report noted decreased expression of the type 2 VMAT gene in platelets from PD patients (27), although it is unclear whether this pattern is shared in cardiac sympathetic neurons. There are several other ways that vesicular uptake could be compromised.…”

Genetic Association Analysis of 300 Genes Identifies a Risk Haplotype in SLC18A2 for Post-traumatic Stress Disorder in Two Independent Samples

“…SLC18A2, also known as VMAT2, is responsible for transporting monoamine neurotransmitters (serotonin, noradrenaline, dopamine) into synaptic vesicles (Erickson et al, 1996). It has been implicated in several complex disorders including Parkinson's disease (Sala et al, 2010), depression (Christiansen et al, 2007), alcohol, and nicotine dependence (Schwab et al, 2005), prostate cancer (Sorensen et al, 2009), and Tourette's syndrome (Ben-Dor et al, 2007). SLC18A2 is also the target of reserpine and tetrabenazine (Peter et al, 1993), drugs used to treat high blood pressure, agitation, tardive dyskinesia, and involuntary movements of Huntington's disease.…”