title: Effects of normal aging and SCN1A risk-gene expression on brain metabolites: evidence for an association between SCN1A and myo-inositol.
abstract: Previously reported MRS findings in the aging brain include lower N-acetylaspartate (NAA) and higher myo-inositol (mI), total creatine (Cr) and choline-containing compound (Cho) concentrations. Alterations in the sodium channel voltage gated type I, alpha subunit SCN1A variant rs10930201 have been reported to be associated with several neurological disorders with cognitive deficits. MRS studies in SCN1A-related diseases have reported striking differences in the mI concentrations between patients and controls. In a study on 'healthy aging', we investigated metabolite spectra in a sample of 83 healthy volunteers and determined their age dependence. We also investigated a potential link between SCN1A and mI. We observed a significantly negative association of NAA (p = 0.004) and significantly positive associations of mI (p ≤ 0.001), Cr (p ≤ 0.001) and Cho (p = 0.034) with age in frontal white matter. The linear association of Cho ends at the age of about 50 years and is followed by an inverted 'U'-shaped curve. Further, mI was higher in C allele carriers of the SCN1A variant rs10930201. Our results corroborated the age-related changes in metabolite concentrations, and found evidence for a link between SCN1A and frontal white matter mI in healthy subjects.
authors.affiliation: Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty of Mannheim/Heidelberg University, Germany.
authors.forename: Nuran
authors.initials: N
authors.lastname: Tunc-Skarka
authors.forename: Sandra
authors.initials: S
authors.lastname: Meier
authors.forename: Traute
authors.initials: T
authors.lastname: Demirakca
authors.forename: Markus
authors.initials: M
authors.lastname: Sack
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weber-Fahr
authors.forename: Wencke
authors.initials: W
authors.lastname: Brusniak
authors.forename: Isabella
authors.initials: I
authors.lastname: Wolf
authors.forename: Franziska
authors.initials: F
authors.lastname: Matthäus
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Schulze
authors.forename: Carsten
authors.initials: C
authors.lastname: Diener
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ende
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000502:physiology*; D019317:Evidence-Based Medicine; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007294:Inositol / Q000235:genetics / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human; D007294:Inositol
keywords: MRS; SCN1A; healthy aging; myo-inositol; white matter