Effects of 3-acetylpyridine on the central nervous system of the rat, as demonstrated by silver methods

Desclin, Jean; Escubi, Jose ́

doi:10.1016/0006-8993(74)90627-1

Cited by 235 publications

(68 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…23 Another potent neurotoxin, 3-acetylpyridine (3-AP), is an electron transport chain uncoupler and is used to selectively model the damage to the dentate gyrus observed following hypoglycemia. [24][25][26] We demonstrate here that, with the use of HSV-mediated gene delivery, anti-apoptotic proteins are sufficient to reduce the hippocampal lesion that develops following KA-induced seizures, but not the damage following 3-AP-modulated metabolic disruption. These results are in agreement with our previous findings in primary hippocampal cultures, in which some of the same inhibitors tested ably protected against a model of domoic acid excitotoxicity, but not the metabolic toxin cyanide.…”

Section: Discussionmentioning

confidence: 99%

HSV-mediated delivery of virally derived anti-apoptotic genes protects the rat hippocampus from damage following excitotoxicity, but not metabolic disruption

2002

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

HSV-mediated delivery of virally derived anti-apoptotic genes protects the rat hippocampus from damage following excitotoxicity, but not metabolic disruption

2002

View full text Add to dashboard Cite

“…3-Acetyl pyridine (3AP) is a toxicant that destroys the inferior olivary nuclei with a single dose (Balaban 1985;Desclin and Escubi 1974) and has been used as a model for cerebellar ataxia (Butterworth et al 1978;Jolicoeur et al 1979). In a comparative study, neuromuscular toxicity was detected using several behavioral tests: the FOB, motor activity, and schedulecontrolled operant responding (Moser and MacPhail 1990).…”

Section: Cerebellarmentioning

confidence: 99%

Functional Assays for Neurotoxicity Testing

Moser

2010

Toxicol Pathol

127

View full text Add to dashboard Cite

Neurobehavioral and pathological evaluations of the nervous system are complementary components of basic research and toxicity testing of pharmaceutical and environmental chemicals. While neuropathological assessments provide insight as to cellular changes in neurons, behavioral and physiological methods evaluate the functional consequences of disruption of neuronal communications. The underlying causes of certain behavioral alterations may be understood, but many do not have known direct associations with specific brain pathologies. In some cases, however, rapidly expanding mouse models (transgenic, knock-out) are providing considerable information on behavioral phenotypes of altered pathology. Behavior represents the integrated sum of activities mediated by the nervous system, and functional tests used for neurotoxicity testing tap different behavioral repertoires. These tests have an advantage over pathologic measures in that they permit repeated evaluation of a single animal over time to determine the onset, progression, duration, and reversibility of a neurotoxic injury. Functional assays range from a screening-level battery of tests to refined procedures to tap specific forms of learning and/or memory. This article reviews common procedures for behavioral toxicity testing and provides examples of chemical-specific neurobehavioral-pathological correlations in order to inform interpretation and integration of neuropathological and behavioral outcomes.

show abstract

“…The neurotoxicity of 3-AP is antagonized by prior or concurrent administration of niacinamide in vivo (Desclin and Escubi, 1974;Simantov et aI., 1976) or in vitro (Weller et aI., 1992), suggesting that 3-AP toxicity is caused by competition of 3-AP with ni acinamide in the formation of NAD and NADP (Herken, 1968;Weller et aI., 1992). The functional depletion of niacinamide leads to a disturbance of hydride ion transfer occurring between enzymes and substrates using NADH and NADPH as a co factor.…”

mentioning

confidence: 99%

“…to the climbing fiber innervation of the cerebellum (Desclin, 1974;Desclin and Escubi, 1974;Balaban, 1985). Therefore, 3-AP has been used extensively to study cerebellar pathophysiology.…”

mentioning

confidence: 99%

“…The 3-AP induced degeneration of the inferior olive and cer ebellum is similar to the pathology seen in olivop ontocerebellar atrophies, a heterogeneous group of disorders, although the neurotoxin does not cause degeneration of the basis pontis. Other target struc tures of 3-AP toxicity include the hippocampal for mation, pars compacta of the substantia nigra with subsequent degeneration of the nigrostriatal projec tions, nucleus ambiguus, hypoglossal nucleus, dor sal motor nucleus of the vagus nerve, interpedun cular nucleus, supraoptic and paraventricular nu clei, and horizontal limb of the nucleus of the diagonal band (Hicks, 1955;Desclin and Escubi, 1974;Balaban, 1985;Deutsch et aI., 1989).…”

mentioning

confidence: 99%

See 1 more Smart Citation

3-Acetylpyridine Produces Age-Dependent Excitotoxic Lesions in Rat Striatum

Schulz

Henshaw²,

Jenkins

et al. 1994

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Summary: The effects of 3-acetylpyridine (3-AP) were studied in rat striatum. Striatal injections of 3-AP pro duced dose-dependent lesions. The lesion size was signif icantly increased in 4-and 12-month-old rats compared to l-month-old rats. Coinjection of the competitive N-meth yl-D-aspartate (NMDA) antagonist 2-amino-5-phosphonovaleric acid (APV) or systemic administration of the noncompetitive NMDA antagonist MK-801, the competitive NMDA antagonist L Y274614, or the gluta mate release inhibitor lamotrigine partially but signifi cantly attenuated striatal lesion volume. Consistent with an NMDA receptor-mediated excitotoxic effect, histo logic studies showed that 3-AP lesions result in relative sparing of NADPH-diaphorase neurons. Using freeze clamp, 3-AP resulted in a marked depletion of ATP. Two-3-Acetylpyridine (3-AP), a niacinamide antago nist, is a potent neurotoxin when administered to laboratory animals by single intraperitoneal injec tions. It induces chronic complex motor and behav ioral abnormalities, which may be seen as hyperk inesias, ataxia, tremor of the front legs, tonic cramps, and spontaneous convulsions (Herken, 1968). 3-AP has been reported to induce degenera tion of the inferior olivary neurons, which give rise

show abstract

Effects of 3-acetylpyridine on the central nervous system of the rat, as demonstrated by silver methods

Cited by 235 publications

References 30 publications

HSV-mediated delivery of virally derived anti-apoptotic genes protects the rat hippocampus from damage following excitotoxicity, but not metabolic disruption

HSV-mediated delivery of virally derived anti-apoptotic genes protects the rat hippocampus from damage following excitotoxicity, but not metabolic disruption

Functional Assays for Neurotoxicity Testing

3-Acetylpyridine Produces Age-Dependent Excitotoxic Lesions in Rat Striatum

Contact Info

Product

Resources

About