Tags

Type your tag names separated by a space and hit enter

Evidence for a dissociation between MPTP toxicity and tyrosinase activity based on congenic mouse strain susceptibility.
Exp Neurol. 2001 Mar; 168(1):116-22.EN

Abstract

The neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is one of the most valuable available models for investigating critical aspects of human Parkinson's disease. In order to analyze the relevance of pigmentation for MPTP sensitivity, we compared C57Bl/6 wild-type mice with the albino mutant C57Bl/6J-Tyr(c-2J) of the same strain. These animals were treated either with systemic MPTP or with saline and were examined in behavioral tests. Seven days after treatment, the contents of dopamine and other monoamines were determined postmortem in the neostriatum and ventral striatum. Furthermore, the numbers of tyrosine hydroxylase-positive cells were counted in the substantia nigra and ventral tegmental area. Open field testing showed that rearing activity was drastically reduced as an acute effect of MPTP in both wild type and mutants; however, subsequent recovery to control levels was faster in wild-type mice. Nest building also indicated strain-dependent effects, since it was delayed only in mutants treated with MPTP. Neurochemically, MPTP led to severe neostriatal dopamine depletions, which did not differ significantly between wild-type (72.9%) and mutant mice (82.1%). Less severe dopamine depletions were also found in the ventral striatum. Histologically, a loss of tyrosine hydroxylase-labeled cells was observed only in the substantia nigra of both wild-type and mutant mice (13.3 and 21.3%, respectively), but not in the ventral tegmental area. Together, our data do not provide evidence that tyrosinase-deficient mice are less affected by MPTP treatment than the comparable wild type, thus arguing strongly against the hypothesis that enhanced MPTP sensitivity in pigmented mouse strains is caused by tyrosinase activity.

Authors+Show Affiliations

Department of Neurology, Heinrich-Heine-University of Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.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

Language

eng

PubMed ID

11170726

Citation

Hofele, K, et al. "Evidence for a Dissociation Between MPTP Toxicity and Tyrosinase Activity Based On Congenic Mouse Strain Susceptibility." Experimental Neurology, vol. 168, no. 1, 2001, pp. 116-22.
Hofele K, Sedelis M, Auburger GW, et al. Evidence for a dissociation between MPTP toxicity and tyrosinase activity based on congenic mouse strain susceptibility. Exp Neurol. 2001;168(1):116-22.
Hofele, K., Sedelis, M., Auburger, G. W., Morgan, S., Huston, J. P., & Schwarting, R. K. (2001). Evidence for a dissociation between MPTP toxicity and tyrosinase activity based on congenic mouse strain susceptibility. Experimental Neurology, 168(1), 116-22.
Hofele K, et al. Evidence for a Dissociation Between MPTP Toxicity and Tyrosinase Activity Based On Congenic Mouse Strain Susceptibility. Exp Neurol. 2001;168(1):116-22. PubMed PMID: 11170726.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for a dissociation between MPTP toxicity and tyrosinase activity based on congenic mouse strain susceptibility. AU - Hofele,K, AU - Sedelis,M, AU - Auburger,G W, AU - Morgan,S, AU - Huston,J P, AU - Schwarting,R K, PY - 2001/2/15/pubmed PY - 2001/4/3/medline PY - 2001/2/15/entrez SP - 116 EP - 22 JF - Experimental neurology JO - Exp Neurol VL - 168 IS - 1 N2 - The neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is one of the most valuable available models for investigating critical aspects of human Parkinson's disease. In order to analyze the relevance of pigmentation for MPTP sensitivity, we compared C57Bl/6 wild-type mice with the albino mutant C57Bl/6J-Tyr(c-2J) of the same strain. These animals were treated either with systemic MPTP or with saline and were examined in behavioral tests. Seven days after treatment, the contents of dopamine and other monoamines were determined postmortem in the neostriatum and ventral striatum. Furthermore, the numbers of tyrosine hydroxylase-positive cells were counted in the substantia nigra and ventral tegmental area. Open field testing showed that rearing activity was drastically reduced as an acute effect of MPTP in both wild type and mutants; however, subsequent recovery to control levels was faster in wild-type mice. Nest building also indicated strain-dependent effects, since it was delayed only in mutants treated with MPTP. Neurochemically, MPTP led to severe neostriatal dopamine depletions, which did not differ significantly between wild-type (72.9%) and mutant mice (82.1%). Less severe dopamine depletions were also found in the ventral striatum. Histologically, a loss of tyrosine hydroxylase-labeled cells was observed only in the substantia nigra of both wild-type and mutant mice (13.3 and 21.3%, respectively), but not in the ventral tegmental area. Together, our data do not provide evidence that tyrosinase-deficient mice are less affected by MPTP treatment than the comparable wild type, thus arguing strongly against the hypothesis that enhanced MPTP sensitivity in pigmented mouse strains is caused by tyrosinase activity. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/11170726/Evidence_for_a_dissociation_between_MPTP_toxicity_and_tyrosinase_activity_based_on_congenic_mouse_strain_susceptibility_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(00)97588-5 DB - PRIME DP - Unbound Medicine ER -