Peripheral blood α-synuclein mRNA levels are elevated in cynomolgus monkeys that chronically self-administer ethanol

Stephen J. Walker, Kathleen (Kathy) Grant

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The gene SNCA (or NACP), which codes for α-synuclein, a small synaptic protein involved in dopaminergic neurotransmission, maps to a quantitative trait locus for alcohol preference and is differentially expressed in specific brain regions in alcohol-preferring versus -nonpreferring rats. Moreover, elevated α-synuclein messenger RNA (mRNA) and protein levels in peripheral blood have been shown to be associated with craving in patients with alcoholism. The focus of this study was to evaluate gene expression, including the levels of α-synuclein mRNA, in peripheral blood in nonhuman primates that were induced to drink ethanol (4 months) and then allowed 14 months of 22-h/day access to ethanol (4% wt/vol) or water compared to alcohol-naïve controls. Differential gene expression, including α-synuclein mRNA levels, was measured in 18 cynomolgus macaque monkeys, 8 that had been chronically self-administering ethanol for 18 months and 10 that were alcohol naïve. Cynomolgus monkeys in this study self-administered ethanol at average rates of between 1.2 and 4.2 g/kg/day. This group of ethanol-drinking monkeys had a highly significant 3.21-fold higher level of α-synuclein mRNA in peripheral blood than alcohol-naïve controls. These data agree with recent reports of elevated α-synuclein mRNA and protein in the blood of human alcoholics, support the concept of an association between α-synuclein and alcoholism, and demonstrate, for the first time, a biomarker present in rats, monkeys, and humans for the consumption of ethanol.

Original languageEnglish (US)
Pages (from-to)1-4
Number of pages4
JournalAlcohol
Volume38
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

Fingerprint

Synucleins
Macaca fascicularis
Blood
Ethanol
alcohol
Messenger RNA
alcoholism
Alcohols
Gene expression
Alcoholism
Haplorhini
Rats
Gene Expression
Proteins
brain
Quantitative Trait Loci
Macaca
Biomarkers
Alcoholics
Synaptic Transmission

Keywords

  • α-Synuclein mRNA
  • Alcoholism
  • Animal model
  • Blood
  • Gene expression
  • Self-administration

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Behavioral Neuroscience
  • Neuroscience(all)
  • Toxicology
  • Health(social science)

Cite this

Peripheral blood α-synuclein mRNA levels are elevated in cynomolgus monkeys that chronically self-administer ethanol. / Walker, Stephen J.; Grant, Kathleen (Kathy).

In: Alcohol, Vol. 38, No. 1, 01.2006, p. 1-4.

Research output: Contribution to journalArticle

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abstract = "The gene SNCA (or NACP), which codes for α-synuclein, a small synaptic protein involved in dopaminergic neurotransmission, maps to a quantitative trait locus for alcohol preference and is differentially expressed in specific brain regions in alcohol-preferring versus -nonpreferring rats. Moreover, elevated α-synuclein messenger RNA (mRNA) and protein levels in peripheral blood have been shown to be associated with craving in patients with alcoholism. The focus of this study was to evaluate gene expression, including the levels of α-synuclein mRNA, in peripheral blood in nonhuman primates that were induced to drink ethanol (4 months) and then allowed 14 months of 22-h/day access to ethanol (4{\%} wt/vol) or water compared to alcohol-na{\"i}ve controls. Differential gene expression, including α-synuclein mRNA levels, was measured in 18 cynomolgus macaque monkeys, 8 that had been chronically self-administering ethanol for 18 months and 10 that were alcohol na{\"i}ve. Cynomolgus monkeys in this study self-administered ethanol at average rates of between 1.2 and 4.2 g/kg/day. This group of ethanol-drinking monkeys had a highly significant 3.21-fold higher level of α-synuclein mRNA in peripheral blood than alcohol-na{\"i}ve controls. These data agree with recent reports of elevated α-synuclein mRNA and protein in the blood of human alcoholics, support the concept of an association between α-synuclein and alcoholism, and demonstrate, for the first time, a biomarker present in rats, monkeys, and humans for the consumption of ethanol.",
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