Metabonomic Characterization of the 3-Nitropropionic Acid Rat Model of Huntington’s Disease

• Published in: Neurochemical research Vol. 34; no. 7; pp. 1261 - 1271
• Main Authors: Tsang, T. M., Haselden, J. N., Holmes, E.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.07.2009; Springer Nature B.V
• Subjects: Animals; Behavior, Animal - drug effects; Biochemistry; Biomedical and Life Sciences; Biomedicine; Brain - metabolism; Brain Stem - metabolism; Cell Biology; Cerebellum - metabolism; Cerebral Cortex - metabolism; Choline - metabolism; Corpus Striatum - metabolism; Disease Models, Animal; gamma-Aminobutyric Acid - metabolism; Hippocampus - metabolism; Huntington Disease - chemically induced; Huntington Disease - metabolism; Lactic Acid - metabolism; Male; Metabolomics; Neurochemistry; Neurology; Neurosciences; Nitro Compounds; Nuclear Magnetic Resonance, Biomolecular - methods; Original Paper; Phosphorylcholine - metabolism; Propionates; Rats; Rats, Sprague-Dawley; Succinic Acid - metabolism; Taurine - physiology; Mitochondria; Choline; Huntington’s disease (HD); Metabonomics; Succinate; Magic-angle-spinning (MAS); Acetylaspartate (NAA); 3-Nitropropionic acid (3-NP); Acetylaspartylglutamate (NAAG); NMR spectroscopy; γ-Amino-butyric acid (GABA)
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-008-9904-5

3-Nitropropionic acid (3-NP)-induced neurotoxicity can be used as a model for the genetic neurodegenerative disorder Huntington’s disease (HD). A metabolic profiling strategy was adopted to explore the biochemical consequences of 3-NP administered to rats in specific brain regions. 1 H NMR spectroscopy was used to characterize the metabolite composition of several brain regions following 3-NP-intoxication. Dose-dependent increases in succinate levels were observed in all neuroanatomical regions, resulting from the 3-NP-induced inhibition of succinate dehydrogenase. Global decreases in taurine and GABA were observed in the majority of brain regions, whereas altered lipid profiles were observed only in the globus pallidus and dorsal striatum. Depleted phosphatidylcholine and elevated glycerol levels, which are indicative of apoptosis, were also observed in the frontal cortex of the 3-NP model. Many of the metabolic anomalies are consistent with those reported in HD. The 3-NP-induced model of HD provides a means of monitoring potential mechanisms of pathology and therapeutic response for drug interventions, which can be efficiently assessed using metabolic profiling strategies.