Specific lesions in the extrapyramidal system of the rat brain induced by 3-nitropropionic acid (3-NPA)

Specific lesions in the extrapyramidal system of the rat brain induced by 3-nitropropionic acid... The irreversible mitochondrial toxin 3-nitropropionic acid (3-NPA) is a specific inhibitor of succinate dehydrogenase. We performed stereotaxic unilateral injections of 3-NPA into the nigrostriatal dopaminergic pathway in rats in order to examine its specific effects on the dopamine system. The 3-NPA-treated rats displayed unidirectional apomorphineinduced rotations, suggesting that 3-NPA selectively damages dopaminergic neurons when injected into the nigrostriatal pathway. In situ hybridization 7 weeks postinjection indicated a decrease in tyrosine hydroxylase (TH) mRNA to 30% of the noninjected side in the substantia nigra pars compacta ( P < 0.05) and decreased to 62% of the noninjected side in the ventral tegmental area (VTA) (nonsignificant) of 3-NPA-lesioned rats. The number of TH mRNA positive cells showed statistically significant decreases in substantia nigra and VTA ( P < 0.001) within the lesioned side. In contrast, expression of mRNAs encoding choline acetyltransferase, p75 low-affinity NGF receptor, neurotrophin tyrosine kinase receptors Trk and TrkB, and brain-derived neurotrophic factor showed neuronal sparing in several other regions of the brain. The results suggest that the nigrostriatal dopaminergic system might be selectively vulnerable to 3-NPA and demonstrate that it is possible to employ 3-NPA in a model of partial lesion of the nigrostriatal dopaminergic system resembling early stages of Parkinson's disease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Experimental Neurology Elsevier

Specific lesions in the extrapyramidal system of the rat brain induced by 3-nitropropionic acid (3-NPA)

Experimental Neurology, Volume 132 (1) – Mar 1, 1995

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Publisher
Elsevier
Copyright
Copyright © 1995 Elsevier Ltd
ISSN
0014-4886
D.O.I.
10.1016/0014-4886(95)90064-0
Publisher site
See Article on Publisher Site

Abstract

The irreversible mitochondrial toxin 3-nitropropionic acid (3-NPA) is a specific inhibitor of succinate dehydrogenase. We performed stereotaxic unilateral injections of 3-NPA into the nigrostriatal dopaminergic pathway in rats in order to examine its specific effects on the dopamine system. The 3-NPA-treated rats displayed unidirectional apomorphineinduced rotations, suggesting that 3-NPA selectively damages dopaminergic neurons when injected into the nigrostriatal pathway. In situ hybridization 7 weeks postinjection indicated a decrease in tyrosine hydroxylase (TH) mRNA to 30% of the noninjected side in the substantia nigra pars compacta ( P < 0.05) and decreased to 62% of the noninjected side in the ventral tegmental area (VTA) (nonsignificant) of 3-NPA-lesioned rats. The number of TH mRNA positive cells showed statistically significant decreases in substantia nigra and VTA ( P < 0.001) within the lesioned side. In contrast, expression of mRNAs encoding choline acetyltransferase, p75 low-affinity NGF receptor, neurotrophin tyrosine kinase receptors Trk and TrkB, and brain-derived neurotrophic factor showed neuronal sparing in several other regions of the brain. The results suggest that the nigrostriatal dopaminergic system might be selectively vulnerable to 3-NPA and demonstrate that it is possible to employ 3-NPA in a model of partial lesion of the nigrostriatal dopaminergic system resembling early stages of Parkinson's disease.

Journal

Experimental NeurologyElsevier

Published: Mar 1, 1995

References

  • Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses?
    Beal, M.F.
  • Complete sequence of a cDNA encoding an active rat choline acetyltransferase: A tool to investigate the plasticity of cholinergic phenotype expression
    Brice, A.; Berrard, S.; Raynaud, B.; Anseau, S.; Coppola, T.; Weber, M.J.; Mallet, J.
  • Function and evolution of the NGF family and its receptors
    Ebendal, T.
  • Striatal degeneration induced by mitochondrial blockade is prevented by biologically delivered NGF
    Frim, D.M.; Simpson, J.; Uhler, T.A.; Short, M.P.; Bossi, S.R.; Breakfield, X.O.; Isacson, O.
  • Basal ganglia degeneration, myelin alterations, and enzyme inhibition induced in mice by the plant toxin 3-nitropropanoic acid
    Gould, D.H.; Gustine, D.L.

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