Attenuation of MPTP-induced neurotoxicity and behavioural impairment in NSE-XIAP transgenic mice.
X-linked IAP protein is a potent inhibitor of cell death. Here, we describe a novel transgenic mouse in which the human XIAP gene is expressed under the control of the neuron-specific enolase promoter (NSE-xiap). We demonstrate that nigrostriatal dopamine neurons of NSE-xiap mice were resistant to the damaging effects of the dopaminergic neurotoxin MPTP. MPTP-induced reduction of striatal dopamine metabolism was also attenuated in NSE-xiap mice. Furthermore, NSE-xiap mice treated with MPTP did not exhibit deficits in exploratory behaviour in an open-field test. Taken together, these findings suggest that strategies to enhance neuronal expression of XIAP may provide therapeutic benefit for the treatment of neurodegeneration in Parkinson's disease.
Crocker
S J
SJ
Neuroscience Research Institute, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada. crocker@scripps.edu
Liston
P
P
Anisman
H
H
Lee
C J
CJ
Smith
P D
PD
Earl
N
N
Thompson
C S
CS
Park
D S
DS
Korneluk
R G
RG
Robertson
G S
GS
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000235:genetics*; D004298:Dopamine / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D010751:Phosphopyruvate Hydratase / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051636:X-Linked Inhibitor of Apoptosis Protein
D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D010751:Phosphopyruvate Hydratase; D004298:Dopamine