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Oxidative metabolism and acetylcholine synthesis during acetylpyridine treatment

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Abstract

In order to clarify the mechanisms by which nicotinic acid deficiency impairs brain function, the effects of the nicotinic acid antimetabolite, 3-acetylpyridine, have been investigated on behavior, cerebral oxidative metabolism, and acetylcholine synthesis. In young rats (21–23 days old), 3-acetylpyridine caused dose- and time-related deficits in behavior, as measured by a neurological scale and by “tight-rope” performance, loss of body weight, and decreased survival. An intermediate dosage decreased cerebral glucose utilization in the inferior olivary nuclei, but increased it in the fastigial, interpositus, red, dentate, vestibular, posterior mamillary, and habenular nuclei. Selective alteration of metabolism was also observed in brain slices from 3-acetylpyridine-treated rats. Although forebrain slices were unaffected, in brainstem slices the synthesis of acetylcholine decreased by 34% with depolarizing (31 mM) concentrations of K+ (P<0.05). This dose of 3-acetylpyridine did not deplete the total pool of NAD in any of the 7 brain regions examined. Thus, the nicotinic acid deficiency which results from 3-acetylpyridine treatment appears to be yet another metabolic encephalopathy in which cholinergic systems are impaired.

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  1. Altschul Laboratory for Dementia Research, Cornell University Medical College Burke Rehabilitation Center, 785 Mamaroneck Avenue, 10605, White Plains, New York

    Gary E. Gibson & John P. Blass

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Gibson, G.E., Blass, J.P. Oxidative metabolism and acetylcholine synthesis during acetylpyridine treatment. Neurochem Res 10, 453–467 (1985). https://doi.org/10.1007/BF00964650

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