Metabolic changes in rat brain following intracerebroventricular injections of streptozotocin: a model of sporadic Alzheimer's disease

Acta Neurochir Suppl. 2010;106:177-81. doi: 10.1007/978-3-211-98811-4_32.

Abstract

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) 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 (1)H 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 microL 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 months some of these changes were even more pronounced. We conclude that in vivo (1)H 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / chemically induced*
  • Alzheimer Disease / pathology*
  • Amino Acids / metabolism
  • Animals
  • Aspartic Acid / analogs & derivatives
  • Brain / drug effects
  • Brain / metabolism*
  • Brain Chemistry / drug effects
  • Disease Models, Animal
  • Electrons
  • Glucose
  • Glutathione
  • Injections, Intraventricular / methods
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Rats
  • Rats, Wistar
  • Streptozocin* / pharmacology

Substances

  • Amino Acids
  • Aspartic Acid
  • Streptozocin
  • N-acetylaspartate
  • Glutathione
  • Glucose