Polyol profiles in Down syndrome. myo-Inositol, specifically, is elevated in the cerebrospinal fluid.

Abstract

Polyols are reduction products of aldoses and ketoses; their concentrations in tissues can reflect carbohydrate metabolism. Several polyol species were quantitated in cerebrospinal fluid (CSF) and plasma from 10 Down Syndrome (trisomy 21) subjects between the ages of 22 and 63 years (3 of whom were demented) and from 10 healthy age-matched controls, using a gas chromatographic/mass spectrometric technique. The mean CSF concentration and the mean CSF/ plasma concentration ratio of myo-inositol were significantly elevated in Down syndrome compared with controls, but were not correlated with the presence of dementia in the Down subjects. Plasma myo-inositol was not significantly altered in these subjects. No significant difference between Down syndrome and controls was found for CSF concentrations of mannitol, sorbitol, galactitol, ribitol, arabitol, or 1,5-anhydrosorbitol, but plasma mannitol, ribitol and arabitol were elevated in Down syndrome. The present observation provides new impetus for studying synthesis and transport of myo-inositol as well as phosphatidylinositol cycle in trisomy 21 disorder. (J. Clin. Invest. 1995. 95:542-546.)

G-Protein-Associated Signal Transduction Processes Are Restored after Postweaning Environmental Enrichment in Ts65Dn, a Down Syndrome Mouse Model

“…Consistent changes found in myoinositol and phospholipid composition of fetal and adult DS brain membranes [25,26,27] may predict deregulation of PLC-linked transduction processes, and our previous studies determined a reduced ability of several brain areas to respond to the indirect (receptor-mediated) and direct stimulation of the PLC [28] and AC [29,30] signaling systems in Ts65Dn mice. In fact, neurotransmitters using these second messenger systems, such as the serotonergic, noradrenergic, GABAergic, and cholinergic systems, are altered in trisomic mice and DS fetuses [30,31,32,33,34,35,36,37], that may compromise short-term memory and hippocampal function [38].…”

Murine chromosome 16 telomeric region, homologous with human chromosome 21q22, contains the osmoregulatory Na⁺/myo-inositol cotransporter (SLC5A3) gene

“…Similar to human Down syndrome (Berry et al, 1999;Shetty et al, 1995), murine trisomy 16 fetuses have increased brain and cerebrospinal fluid MI levels (Shetty et al, 1996). Also, similar to trisomic 21 fibroblasts (Fruen and Lester, 1990), there is an increased rate of MI uptake by cultured cortical neurons from trisomy 16 mice (Acevedo et al, 1997).…”

“…We have limited understanding of the role altered MI levels may play in the pathogenesis of human trisomy 21 or murine trisomy 16. Altered volume regulation, organic osmolyte, and ion composition in neural cells (Berry et al, 1995) have been considered as potential consequences of the extra SLC5A3/Slc5a3 gene copy number and increased MI transport and levels, while alterations in signaling pathways (Shetty et al, 1995) are believed to be the effect of increased cellular MI levels on phosphoinositide synthesis. From an energy viewpoint, the increased influx and efflux of MI across the plasma membrane may constitute a futile cycle involving at least two distinct transport systems.…”

CSF inositol does not predict antidepressant response to inositol

“…Since cellular inositol subserves several functions in different pools, including an osmolyte pool and a precursor pool for PI synthesis , CSF inositol may equilibrate with cellular inositol unrelated to neuronal function. Shetty et al (1995) found that the triple dose of inositol transporter felt to be present in Down's syndrome because the gene for the inositol transporter is on chromosome 21, is expressed as an elevated CSF inositol level.…”