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

Abstract：

:3-Nitropropionic acid (3-NPA) is a toxin sometimes produced on moldy crops (sugarcane, peanuts, etc.) in amounts sufficient to cause severe neurological disorders when consumed by humans. In vitro, 3-NPA irreversibly inactivates 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-caged adult male Sprague-Dawley rats. Rectal temperature was measured after dosing as a potential biomarker of exposure to 3-NPA, and animals were sacrificed at various times after 3-NPA exposure for histochemical visualization of SDH activity. 3-NPA-treated rats experienced a progressive hypothermia, which reached a loss of 3 degrees C or more in core body temperature by 3 hours 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 density of SDH staining that we measured in brain; it also has been reported to be the region most consistently lesioned by 3-NPA. However, within other areas of brain such as subdivisions of the hippocampus, neither endogenous SDH activity nor its sensitivity to inhibition by 3-NPA could predict the susceptibility to neurodegenerative changes. Although SDH activity remained significantly reduced in most areas of brain (except thalamus) for up to 5 days 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.

journal_name

Metab Brain Dis

journal_title

Metabolic brain disease

authors

Nony PA,Scallet AC,Rountree RL,Ye X,Binienda Z

doi

10.1023/a:1020753629477

subject

Has Abstract

pub_date

1999-06-01 00:00:00

pages

83-94

issue

2

eissn

0885-7490

issn

1573-7365

journal_volume

14

pub_type

杂志文章

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