Attenuation of MPTP-induced neurotoxicity and behavioural impairment in NSE-XIAP transgenic mice

S. J. Crocker; P. Liston; H. Anisman; C. J. Lee; P. D. Smith; N. Earl; C. S. Thompson; D. S. Park; R. G. Korneluk; G. S. Robertson

doi:10.1016/S0969-9961(02)00020-7

Attenuation of MPTP-induced neurotoxicity and behavioural impairment in NSE-XIAP transgenic mice

S. J. Crocker, P. Liston, H. Anisman, C. J. Lee, P. D. Smith, N. Earl, C. S. Thompson, D. S. Park, R. G. Korneluk, G. S. Robertson

Résultat de recherche: Article › examen par les pairs

53 Citations (Scopus)

Résumé

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.

Langue d'origine	English
Pages (de-à)	150-161
Nombre de pages	12
Journal	Neurobiology of Disease
Volume	12
Numéro de publication	2
DOI	https://doi.org/10.1016/S0969-9961(02)00020-7
Statut de publication	Published - mars 2003
Publié à l'externe	Oui

Note bibliographique

Funding Information:
We thank A. Adeeko and Y. Zhu for expert technical assistance. S.J.C. was supported by an Ontario Neurotrauma Foundation Postdoctoral Fellowship. D.S.P. is a Canadian Institutes of Health Research (CIHR) Scholar. R.G.K. is a Howard Hughes Medical Institute International Research Scholar and CIHR Senior Scientist. H.A. holds a Canada Research Chair in Neuroscience. This work was supported by grants from the Canadian Institutes of Health Research (G.S.R. and R.G.K.) and the Ontario Neurotrauma Foundation (to D.S.P. and G.S.R.).

ASJC Scopus Subject Areas

Neurology

ODD de l’ONU

Cette action contribue à la réalisation des objectifs de développement durable suivants

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10.1016/S0969-9961(02)00020-7

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title = "Attenuation of MPTP-induced neurotoxicity and behavioural impairment in NSE-XIAP transgenic mice",

abstract = "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.",

author = "Crocker, {S. J.} and P. Liston and H. Anisman and Lee, {C. J.} and Smith, {P. D.} and N. Earl and Thompson, {C. S.} and Park, {D. S.} and Korneluk, {R. G.} and Robertson, {G. S.}",

note = "Funding Information: We thank A. Adeeko and Y. Zhu for expert technical assistance. S.J.C. was supported by an Ontario Neurotrauma Foundation Postdoctoral Fellowship. D.S.P. is a Canadian Institutes of Health Research (CIHR) Scholar. R.G.K. is a Howard Hughes Medical Institute International Research Scholar and CIHR Senior Scientist. H.A. holds a Canada Research Chair in Neuroscience. This work was supported by grants from the Canadian Institutes of Health Research (G.S.R. and R.G.K.) and the Ontario Neurotrauma Foundation (to D.S.P. and G.S.R.). ",

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AU - Crocker, S. J.

AU - Liston, P.

AU - Anisman, H.

AU - Lee, C. J.

AU - Smith, P. D.

AU - Earl, N.

AU - Thompson, C. S.

AU - Park, D. S.

AU - Korneluk, R. G.

AU - Robertson, G. S.

N1 - Funding Information: We thank A. Adeeko and Y. Zhu for expert technical assistance. S.J.C. was supported by an Ontario Neurotrauma Foundation Postdoctoral Fellowship. D.S.P. is a Canadian Institutes of Health Research (CIHR) Scholar. R.G.K. is a Howard Hughes Medical Institute International Research Scholar and CIHR Senior Scientist. H.A. holds a Canada Research Chair in Neuroscience. This work was supported by grants from the Canadian Institutes of Health Research (G.S.R. and R.G.K.) and the Ontario Neurotrauma Foundation (to D.S.P. and G.S.R.).

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N2 - 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.

AB - 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.

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Attenuation of MPTP-induced neurotoxicity and behavioural impairment in NSE-XIAP transgenic mice

Résumé

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ODD de l’ONU

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