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The neurotoxin MPTP causes degeneration of specific nucleus A8, A9 and A10 dopaminergic neurons in the mouse.
Neurodegeneration. 1996 Dec; 5(4):299-312.N

Abstract

The neurotoxin MPTP has been used to create an animal model of Parkinson's disease in the mouse, in part, because it causes a significant loss of dopaminergic neurons in the substantia nigra (nucleus A9). The purpose of the present study was to determine whether MPTP also causes degeneration of midbrain dopaminergic neurons in nuclei A8 and A10 in the mouse, as occurs in humans with Parkinson's disease. Two commonly used strains of mice were used: FVB/N and C57BL/6. MPTP was administered in cumulative doses of 50-300 mg/kg. Seven days later, dopamine concentrations were measured in the striatum using high performance liquid chromatography, and midbrain dopaminergic neurons were identified using an antibody against tyrosine hydroxylase. The cell locations were mapped with a computer imaging system. In the FVB/N strain, there was a dose-dependent decrease in striatal dopamine concentrations. Although the highest dose (300 mg/kg) caused an 86% reduction in striatal dopamine concentrations, there was only a moderate and non-significant loss of midbrain dopaminergic neurons. In the C57BL/6 strain, however, a high dose of MPTP (240 mg/kg) caused a significant reduction in both striatal dopamine concentrations (95%), and midbrain dopaminergic cells; 69% loss of nucleus A8 cells, 75% loss of nucleus A9 cells, and in nucleus A10 subnuclei there was 42% loss of ventral tegmental area cells, 55% loss of interfascicular nucleus cells, and no loss of cells in the central linear nucleus. These data (1) provide further evidence for differential susceptibility to MPTP toxicity among different mouse strains, (2) indicate that a significant depletion of striatal dopamine is not necessarily due to degeneration of midbrain dopaminergic neurons, (3) provide the precise locations of midbrain dopaminergic cells that are vulnerable to MPTP, which will aid future studies that seek to determine the mechanism/s by which-MPTP selectively destroys only certain midbrain dopaminergic neurons, and (4) indicate that MPTP produces midbrain dopaminergic neuronal degeneration in the same nuclei in the C57BL16 mouse that degenerate in humans with Parkinson's disease.

Authors+Show Affiliations

Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75235-9070, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9117541

Citation

German, D C., et al. "The Neurotoxin MPTP Causes Degeneration of Specific Nucleus A8, A9 and A10 Dopaminergic Neurons in the Mouse." Neurodegeneration : a Journal for Neurodegenerative Disorders, Neuroprotection, and Neuroregeneration, vol. 5, no. 4, 1996, pp. 299-312.
German DC, Nelson EL, Liang CL, et al. The neurotoxin MPTP causes degeneration of specific nucleus A8, A9 and A10 dopaminergic neurons in the mouse. Neurodegeneration. 1996;5(4):299-312.
German, D. C., Nelson, E. L., Liang, C. L., Speciale, S. G., Sinton, C. M., & Sonsalla, P. K. (1996). The neurotoxin MPTP causes degeneration of specific nucleus A8, A9 and A10 dopaminergic neurons in the mouse. Neurodegeneration : a Journal for Neurodegenerative Disorders, Neuroprotection, and Neuroregeneration, 5(4), 299-312.
German DC, et al. The Neurotoxin MPTP Causes Degeneration of Specific Nucleus A8, A9 and A10 Dopaminergic Neurons in the Mouse. Neurodegeneration. 1996;5(4):299-312. PubMed PMID: 9117541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The neurotoxin MPTP causes degeneration of specific nucleus A8, A9 and A10 dopaminergic neurons in the mouse. AU - German,D C, AU - Nelson,E L, AU - Liang,C L, AU - Speciale,S G, AU - Sinton,C M, AU - Sonsalla,P K, PY - 1996/12/1/pubmed PY - 1996/12/1/medline PY - 1996/12/1/entrez SP - 299 EP - 312 JF - Neurodegeneration : a journal for neurodegenerative disorders, neuroprotection, and neuroregeneration JO - Neurodegeneration VL - 5 IS - 4 N2 - The neurotoxin MPTP has been used to create an animal model of Parkinson's disease in the mouse, in part, because it causes a significant loss of dopaminergic neurons in the substantia nigra (nucleus A9). The purpose of the present study was to determine whether MPTP also causes degeneration of midbrain dopaminergic neurons in nuclei A8 and A10 in the mouse, as occurs in humans with Parkinson's disease. Two commonly used strains of mice were used: FVB/N and C57BL/6. MPTP was administered in cumulative doses of 50-300 mg/kg. Seven days later, dopamine concentrations were measured in the striatum using high performance liquid chromatography, and midbrain dopaminergic neurons were identified using an antibody against tyrosine hydroxylase. The cell locations were mapped with a computer imaging system. In the FVB/N strain, there was a dose-dependent decrease in striatal dopamine concentrations. Although the highest dose (300 mg/kg) caused an 86% reduction in striatal dopamine concentrations, there was only a moderate and non-significant loss of midbrain dopaminergic neurons. In the C57BL/6 strain, however, a high dose of MPTP (240 mg/kg) caused a significant reduction in both striatal dopamine concentrations (95%), and midbrain dopaminergic cells; 69% loss of nucleus A8 cells, 75% loss of nucleus A9 cells, and in nucleus A10 subnuclei there was 42% loss of ventral tegmental area cells, 55% loss of interfascicular nucleus cells, and no loss of cells in the central linear nucleus. These data (1) provide further evidence for differential susceptibility to MPTP toxicity among different mouse strains, (2) indicate that a significant depletion of striatal dopamine is not necessarily due to degeneration of midbrain dopaminergic neurons, (3) provide the precise locations of midbrain dopaminergic cells that are vulnerable to MPTP, which will aid future studies that seek to determine the mechanism/s by which-MPTP selectively destroys only certain midbrain dopaminergic neurons, and (4) indicate that MPTP produces midbrain dopaminergic neuronal degeneration in the same nuclei in the C57BL16 mouse that degenerate in humans with Parkinson's disease. SN - 1055-8330 UR - https://www.unboundmedicine.com/medline/citation/9117541/The_neurotoxin_MPTP_causes_degeneration_of_specific_nucleus_A8_A9_and_A10_dopaminergic_neurons_in_the_mouse_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1055-8330(96)90041-0 DB - PRIME DP - Unbound Medicine ER -