3-nitropropionic acid (3-NPA) produces hypothermia and inhibits histochemical labeling of succinate dehydrogenase (SDH) in rat brain

3-nitropropionic acid (3-NPA) is a toxin sometimes produced on moldy crops (sugarcane, peanuts, etc.) in amounts sufficient to cause severe neurologic al disorders when consumed by humans. In vitro, 3-NPA irreversibly inactiva tes SDH, a Complex II respiratory enzyme required for mitochondrial energy production. A single dose of 3-NPA (30 mg/kg S.C.) was given to singly-cage d adult male Sprague-Dawley rats. Rectal temperature was measured after dos ing as a potential biomarker of exposure to 3-NPA, and animals were sacrifi ced at various times after 3-NPA exposure for histochemical visualization o f SDH activity. 3-NPA-treated rats experienced a progressive hypothermia, w hich reached a loss of 3 degrees C or more in core body temperature by 3 ho urs after dosing. The optical density of the SDH stain in brain was reduced according to a similar time-course, most prominently in the cerebellum and least sharply in the thalamus. The caudate nucleus had the greatest densit y of SDH staining that we measured in brain; it also has been reported to b e the region most consistently lesioned by 3-NPA. However, within other are as of brain such as subdivisions of the hippocampus, neither endogenous SDH activity nor its sensitivity to inhibition by 3-NPA could predict the susc eptibility to neurodegenerative changes. Although SDH activity remained sig nificantly reduced in most areas of brain (except thalamus) for up to 5 day s after dosing, core temperatures had returned to control values by 5 days suggesting that animals can utilize an alternate method of heat production to withstand insult by 3-NPA.