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          Institute: MPI für Psychiatrie     Collection: Publikationen MPI für Psychiatrie     Display Documents

ID: 475610.0, MPI für Psychiatrie / Publikationen MPI für Psychiatrie
DJ-1-deficient mice show less TH-positive neurons in the ventral tegmental area and exhibit non-motoric behavioural impairments
Authors:Pham, T. T.; Giesert, F.; Rothig, A.; Floss, T.; Kallnik, M.; Weindl, K.; Hölter, S. M.; Ahting, U.; Prokisch, H.; Becker, L.; Klopstock, T.; de Angelis, M. H.; Beyer, K.; Görner, K.; Kahle, P. J.; Vogt-Weisenhorn, D. M.; Wurst, W.
Date of Publication (YYYY-MM-DD):2010-04
Title of Journal:Genes Brain and Behavior
Issue / Number:3
Start Page:305
End Page:317
Review Status:not specified
Audience:Not Specified
Abstract / Description:Loss of function of DJ-1 (PARK7) is associated with autosomal recessive early-onset Parkinson's disease (PD), one of the major age-related neurological diseases. In this study, we extended former studies on DJ-1 knockout mice by identifying subtle morphological and behavioural phenotypes. The DJ-1 gene trap-induced null mutants exhibit less dopamine-producing neurons in the ventral tegmental area (VTA). They also exhibit slight changes in behaviour, i.e. diminished rearing behaviour and impairments in object recognition. Furthermore, we detected subtle phenotypes, which suggest that these animals compensate for the loss of DJ-1. First, we found a significant upregulation of mitochondrial respiratory enzyme activities, a mechanism known to protect against oxidative stress. Second, a close to significant increase in c-Jun N-terminal kinase 1 phosphorylation in old DJ-1-deficient mice hints at a differential activation of neuronal cell survival pathways. Third, as no change in the density of tyrosine hydroxylase (TH)-positive terminals in the striatum was observed, the remaining dopamine-producing neurons likely compensate by increasing axonal sprouting. In summary, the present data suggest that DJ-1 is implicated in major non-motor symptoms of PD appearing in the early phases of the disease-such as subtle impairments in motivated behaviour and cognition-and that under basal conditions the loss of DJ-1 is compensated.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:N. N.
Affiliations:MPI für Psychiatrie
Identifiers:ISI:000276604800006 [ID No:1]
ISSN:1601-1848 [ID No:2]
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