Metabolic Changes in Rat Brain Following Intracerebroventricular Injections of Streptozotocin: A Model of Sporadic Alzhe
A decrease in cerebral glucose metabolic uptake is an early and characteristic sign of Alzheimer’s disease (AD). Streptozotocin (STZ) is a bacterial toxin which damages insulin-producing cells and insulin receptors. Intracerebroventricular (icv) applicati
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bstract A decrease in cerebral glucose metabolic uptake is an early and characteristic sign of Alzheimer’s disease (AD). Streptozotocin (STZ) is a bacterial toxin which damages insulin-producing cells and insulin receptors. Intracerebro ventricular (icv) application of STZ in rats has been found to chronically decrease cerebral glucose uptake and produce other effects that bear a resemblance to several other molecular and pathological features of AD. In the present experiments in vivo 1H MR Spectroscopy with short echo time (3 ms) was used to non-invasively obtain a neurochemical profile of rat brains, 3 weeks and 2 months after double icv injections of STZ or vehicle. Seventeen metabolites were quantified from 27 mL tissue volume which included hippocampus and a part of cerebral cortex, using the LCModel and unsuppressed water signal as an internal reference. Three weeks after icv STZ several metabolites were significantly decreased, the most prominent changes noted in glycerophosphocholine and phosphocholine (−38 ± 5%), glutathione (−37 ± 4%), taurine (−30 ± 19%), glutamate (−26 ± 14%), phosphocreatine (−23 ± 15%) and N-acetylaspartate (−16 ± 6%). On the contrary, the concentration of N-acetylaspartylglutamate was found significantly increased (+38 ± 18%). After 2
M. Labak and A. Jasin´ski Department of Magnetic Resonance Imaging, H. Niewodniczanski Institute of Nuclear Physics, Polish Academy of Sciences, Radzikowskiego 152, Krakow 31-342, Poland T. Foniok, D. Kirk, and D. Rushforth National Research Council of Canada Institute for Biodiagnostics and Experimental Imaging Centre, Calgary, Canada B. Tomanek Department of Magnetic Resonance Imaging, H. Niewodniczanski Institute of Nuclear Physics, Polish Academy of Sciences, Radzikowskiego 152, Krakow 31-342, Poland and National Research Council of Canada Institute for Biodiagnostics and Experimental Imaging Centre, Calgary, Canada P. Grieb () Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland e-mail: [email protected]
months some of these changes were even more pronounced. We conclude that in vivo 1H MRS of rat brain following icv STZ injections provides a new input into a better understanding of the critical dependency of neural function and structure on brain glucose consumption, and may be of relevance in further studies of AD pathomechanism. Keywords Sporadic Alzheimer’s disease • streptozotocin • H-MR spectroscopy • LCModel • neurochemical profile • brain metabolites • MR spectra quantification
Introduction Despite intense research the pathogenesis of Alzheimer disease (AD) remains a matter of debate (1). Currently the most popular “amyloid cascade” hypothesis assumes that the primary pathogenetic event in AD comprises formation of neurotoxic Ab deposits. Another leading hypothesis assumes that the central pathogenetic event in AD is hyperphosphorylation of tau protein which leads to neurofibrillary triangles formation. Both aforementioned hypotheses have in comm
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