Using gas chromatography/mass spectrometry, we found a 50% increase in myo-inositol (MI) concentration in cerebrospinal fluid of Down syndrome (DS) adults. Brain MI concentration also was elevated in trisomy 65Dn mice (a partial trisomy 16 model of DS). A stable isotope technique was developed to measure MI uptake and turnover in cultured cells. Fetal mouse trisomy 16 cortical neurons (compared with diploid neurons) exhibited higher sodium-dependent MI uptake, consistent with the MI transporter gene being on mouse chromosome 16 and human chromosome 21. As MI plays a role in signal transduction involving phosphoinositides, the defect may be related to mental retardation in DS. A new method was developed to examine MI turnover in phosphatidylinositol in cultured neurons in relation to signal transduction.
