3-Nitropropionic acid-induced neurotoxicity - Assessed by ultra high resolution positron emission tomography with comparison to magnetic resonance spectroscopy

Anna Liisa Brownell, Y. Iris Chen, Meixiang Max Yu, Xukui Wang, Alpaslan Dedeoglu, Francesca Cicchetti, Bruce G. Jenkins, M. Flint Beal

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

To explore acute and long-term effects of 3-nitropropionic acid (3-NP)-induced neurotoxicity, longitudinal positron emission tomography (PET) studies of energy metabolism and magnetic resonance spectroscopic (MRS) studies of neurochemicals were conducted in a rat model. The first injection of 3-NP (20 mg/kg i.p.) was followed by MRS study of neurochemicals and PET study of glucose utilization using [18F]2-fluorodeoxy-D-glucose ( 18F-FDG). After that, 3-NP administration was done two times a day with a dose of 10 mg/kg i.p. until animals were symptomatic or for a maximum of 5 days combined with daily PET studies. Long-term effects were investigated 4 weeks and 4 months after cessation of 3-NP. These studies showed a significant interanimal variation in response of 3-NP toxicity. Animals that developed large striatal lesions had decreased glucose utilization in the striatum and cortex 1 day after starting 3-NP injections. Similarly succinate and lactate/macromolecule levels were enhanced; these changes being, however, reversible. Progressive degeneration was observed by decreasing striatal glucose utilization and N-acetylaspartate (NAA) and increasing choline. These observations paralleled with weight loss and deficits in behavior. Animals that did not develop lesions showed reversible enhancement in cortical glucose utilization and no change in striatal glucose utilization or neurochemicals or locomotor activity.

Original languageEnglish (US)
Pages (from-to)1206-1214
Number of pages9
JournalJournal of Neurochemistry
Volume89
Issue number5
DOIs
StatePublished - Jun 1 2004

Keywords

  • 3-Nitropropionic acid
  • Glucose utilization
  • Huntington's disease
  • Magnetic resonance spectroscopy
  • Neurodegeneration
  • Positron emission tomography

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of '3-Nitropropionic acid-induced neurotoxicity - Assessed by ultra high resolution positron emission tomography with comparison to magnetic resonance spectroscopy'. Together they form a unique fingerprint.

Cite this