GABA- and acetylcholine-related gene expression in blood correlate with tic severity and microarray evidence for alternative splicing in Tourette syndrome: A pilot study

Yingfang Tian, Joan R. Gunther, Isaac H. Liao, Da Liu, Bradley Ander, Boryana Stamova, Lisa Lit, Glen C. Jickling, Huichun Xu, Xinhua Zhan, Frank R Sharp

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Tourette syndrome (TS) is a complex childhood neurodevelopmental disorder characterized by motor and vocal tics. Recently, altered numbers of GABAergic-parvalbumin (PV) and cholinergic interneurons were observed in the basal ganglia of individuals with TS. Thus, we postulated that gamma-amino butyric acid (GABA)- and acetylcholine (ACh)-related genes might be associated with the pathophysiology of TS. Total RNA isolated from whole blood of 26 un-medicated TS subjects and 23 healthy controls (HC) was processed on Affymetrix Human Exon 1.0 ST arrays. Data were analyzed to identify genes whose expression correlated with tic severity in TS, and to identify genes differentially spliced in TS compared to HC subjects. Many genes (3627) correlated with tic severity in TS (p < 0.05) among which GABA- (p = 2.1 × 10-3) and ACh- (p = 4.25 × 10-8) related genes were significantly over-represented. Moreover, several GABA and ACh-related genes were predicted to be alternatively spliced in TS compared to HC including GABA receptors GABRA4 and GABRG1, the nicotinic ACh receptor CHRNA4 and cholinergic differentiation factor (CDF). This pilot study suggests that at least some of these GABA- and ACh-related genes observed in blood that correlate with tics or are alternatively spliced are involved in the pathophysiology of TS and tics.

Original languageEnglish (US)
Pages (from-to)228-236
Number of pages9
JournalBrain Research
Volume1381
DOIs
StatePublished - Mar 24 2011

Keywords

  • Acetylcholine
  • Alternative splicing
  • Blood
  • GABA
  • Gene expression profiling
  • Tourette syndrome

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'GABA- and acetylcholine-related gene expression in blood correlate with tic severity and microarray evidence for alternative splicing in Tourette syndrome: A pilot study'. Together they form a unique fingerprint.

  • Cite this