Department of Anesthesiology

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In vitro 1H and 31P NMR spectroscopic evidence of multiple aberrant biochemical pathways in murine trisomy 16 brain development.

TitleIn vitro 1H and 31P NMR spectroscopic evidence of multiple aberrant biochemical pathways in murine trisomy 16 brain development.
Publication TypeJournal Article
Year of Publication2000
AuthorsYao FS, Caserta MT, Wyrwicz AM
JournalInt J Dev Neurosci
Volume18
Issue8
Pagination833-41
Date Published2000 Dec
ISSN0736-5748
KeywordsAlanine, Animals, Aspartic Acid, Biological Markers, Brain Chemistry, Choline, Creatine, Disease Models, Animal, Down Syndrome, Female, gamma-Aminobutyric Acid, Glutamic Acid, Inositol 1,4,5-Trisphosphate, Lactic Acid, Magnetic Resonance Spectroscopy, Male, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Phosphorus Isotopes, Protons, Taurine, Threonine
Abstract

Nuclear magnetic resonance (NMR) spectroscopy was used to evaluate cytosolic compounds and membrane phospholipids simultaneously in trisomy 16 (Ts16) and euploid (control) murine brain at fetal day 15 in order to examine the cellular biochemistry that underlies the neurodevelopmental consequences of chromosome triplication in this model of Down syndrome (DS). Proton NMR spectroscopic analysis of brain tissue extracts demonstrated decreased levels of choline and increased levels of myo-inositol (MI) in Ts16 brains compared with control. These data are consistent with the cholinergic deficits and elevated MI levels previously described in Ts16. Compared with euploid brains. Ts16 brains also possess higher levels of creatine, adenosine, and tyrosine. Increased levels of MI and creatine, compounds that are localized to glia, imply abnormalities in the trophic environment of Ts16 brain. Phosphorus NMR spectroscopic analysis of extracts further revealed elevated levels of anionic phospholipid membrane components, such as phosphatidylinositol (PtdIno) and phosphatidylethanolamine, in Ts16 brains. Since these compounds are confined to the inner leaflet of the membrane, the findings suggest that membrane composition is altered specifically in the cytosolic bilayer at this stage. Together our proton and phosphorus NMR spectroscopic results indicate that multiple biochemical pathways are affected in Ts16 brain development. Understanding the effects of these aberrations may elucidate the processes that lead to neural dysfunction and Alzheimer's disease (AD) neuropathology in DS individuals.

Alternate JournalInt. J. Dev. Neurosci.
PubMed ID11154853
Grant ListK07-01056 / / PHS HHS / United States
R01GM-53175 / GM / NIGMS NIH HHS / United States