Evidence for resistance to MPTP in C57BL/6 × BALA/c F1 hybrids as compared with their progenitor strains
- 1 April 2000
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in NeuroReport
- Vol. 11 (5), 1093-1096
- https://doi.org/10.1097/00001756-200004070-00037
Abstract
The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is capable of producing a syndrome in mice which shares major characteristics with human Parkinson's disease. There is evidence for a genetic influence on the degree of damage exerted by MPTP, since different strains of mice can dramatically differ in their response to MPTP. We produced reciprocal F1 hybrids by crossbreeding the MPTP-susceptible C57BL/6 strain with resistant BALB/c. These hybrids were compared to the parental strains using neural and behavioral measures in order to characterize the genetic transmission of MPTP-susceptibility. The F1 generation as a whole had a lower depletion of neostriatal dopamine levels than even found in BALB/c. Furthermore, there was no significant loss of tyrosine hydroxylase-positive cells in the substantia nigra and quick recovery from deficits in motor behavior in F1, herein resembling BALB/c. We suggest that several loci are involved in susceptibility to MPTP, and that the trait is under control of recessive susceptibility and/or dominant resistance alleles, which interact in F1, leading to extremely low susceptibility.Keywords
This publication has 5 references indexed in Scilit:
- Quantitative Trait Locus Analysis: A New Tool for Psychiatric GeneticsThe Neuroscientist, 1998
- MPTP Produces Differential Oxidative Stress and Antioxidative Responses in the Nigrostriatal and Mesolimbic Dopaminergic PathwaysFree Radical Biology & Medicine, 1998
- Genetic factors in neurotoxicology and neuropharmacology: A critical evaluation of the use of genetics as a research toolCellular and Molecular Life Sciences, 1991
- Strain differences in systematic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity in mice correlate best with monoamine oxidase activity at the blood-brain barrierLife Sciences, 1988
- Short-term effects of ether, equithesin and droperidol/fentanyl on catecholamine and indolamine metabolism in the brain of the ratNeuropharmacology, 1987