Low dose rotenone treatment causes selective transcriptional activation of cell death related pathways in dopaminergic neurons in vivo

Low dose rotenone treatment causes selective transcriptional activation of cell death related pathways in dopaminergic neurons in vivo

Mitochondrial complex I inhibition has been implicated in the degeneration of midbrain dopaminergic (DA) neurons in Parkinson's disease. However, the mechanisms and pathways that determine the cellular fate of DA neurons downstream of the mitochondrial dysfunction have not been fully identified...

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Main Authors: B.H. Meurers, C. Zhu, P.O. Fernagut, F. Richter, Y.C. Hsia, S.M. Fleming, M. Oh, D. Elashoff, C.D. DiCarlo, R.L. Seaman, M.F. Chesselet
Format: Article
Language:English
Published: Elsevier 2009-02-01
Series:Neurobiology of Disease
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996108002519
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spelling doaj-4c80fce8cd8b429cbaaeb7cf4fa1e2c22021-03-20T04:56:41ZengElsevierNeurobiology of Disease1095-953X2009-02-01332182192Low dose rotenone treatment causes selective transcriptional activation of cell death related pathways in dopaminergic neurons in vivoB.H. Meurers0C. Zhu1P.O. Fernagut2F. Richter3Y.C. Hsia4S.M. Fleming5M. Oh6D. Elashoff7C.D. DiCarlo8R.L. Seaman9M.F. Chesselet10Department of Neurology, UCLA, Los Angeles, CA, USA; Corresponding author. Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles CA 90095, USA. Fax: +1 310 267 1786.Department of Neurology, UCLA, Los Angeles, CA, USADepartment of Neurology, UCLA, Los Angeles, CA, USADepartment of Neurology, UCLA, Los Angeles, CA, USADepartment of Neurology, UCLA, Los Angeles, CA, USADepartment of Neurology, UCLA, Los Angeles, CA, USADepartment of Public Health, UCLA, Los Angeles, CA, USADepartment of Public Health, UCLA, Los Angeles, CA, USASouthwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, TX, USAMcKesson BioServices at US Army Medical Research Detachment, Brooks City-Base, TX, USADepartment of Neurology, UCLA, Los Angeles, CA, USA; Department of Neurobiology, UCLA, Los Angeles, CA, USAMitochondrial complex I inhibition has been implicated in the degeneration of midbrain dopaminergic (DA) neurons in Parkinson's disease. However, the mechanisms and pathways that determine the cellular fate of DA neurons downstream of the mitochondrial dysfunction have not been fully identified. We conducted cell-type specific gene array experiments with nigral DA neurons from rats treated with the complex I inhibitor, rotenone, at a dose that does not induce cell death. The genome wide screen identified transcriptional changes in multiple cell death related pathways that are indicative of a simultaneous activation of both degenerative and protective mechanisms. Quantitative PCR analyses of a subset of these genes in different neuronal populations of the basal ganglia revealed that some of the changes are specific for DA neurons, suggesting that these neurons are highly sensitive to rotenone. Our data provide insight into potentially defensive strategies of DA neurons against disease relevant insults.http://www.sciencedirect.com/science/article/pii/S0969996108002519
collection DOAJ
language English
format Article
sources DOAJ
author B.H. Meurers
C. Zhu
P.O. Fernagut
F. Richter
Y.C. Hsia
S.M. Fleming
M. Oh
D. Elashoff
C.D. DiCarlo
R.L. Seaman
M.F. Chesselet
spellingShingle B.H. Meurers
C. Zhu
P.O. Fernagut
F. Richter
Y.C. Hsia
S.M. Fleming
M. Oh
D. Elashoff
C.D. DiCarlo
R.L. Seaman
M.F. Chesselet
Low dose rotenone treatment causes selective transcriptional activation of cell death related pathways in dopaminergic neurons in vivo
Neurobiology of Disease
author_facet B.H. Meurers
C. Zhu
P.O. Fernagut
F. Richter
Y.C. Hsia
S.M. Fleming
M. Oh
D. Elashoff
C.D. DiCarlo
R.L. Seaman
M.F. Chesselet
author_sort B.H. Meurers
title Low dose rotenone treatment causes selective transcriptional activation of cell death related pathways in dopaminergic neurons in vivo
title_short Low dose rotenone treatment causes selective transcriptional activation of cell death related pathways in dopaminergic neurons in vivo
title_full Low dose rotenone treatment causes selective transcriptional activation of cell death related pathways in dopaminergic neurons in vivo
title_fullStr Low dose rotenone treatment causes selective transcriptional activation of cell death related pathways in dopaminergic neurons in vivo
title_full_unstemmed Low dose rotenone treatment causes selective transcriptional activation of cell death related pathways in dopaminergic neurons in vivo
title_sort low dose rotenone treatment causes selective transcriptional activation of cell death related pathways in dopaminergic neurons in vivo
publisher Elsevier
series Neurobiology of Disease
issn 1095-953X
publishDate 2009-02-01
description Mitochondrial complex I inhibition has been implicated in the degeneration of midbrain dopaminergic (DA) neurons in Parkinson's disease. However, the mechanisms and pathways that determine the cellular fate of DA neurons downstream of the mitochondrial dysfunction have not been fully identified. We conducted cell-type specific gene array experiments with nigral DA neurons from rats treated with the complex I inhibitor, rotenone, at a dose that does not induce cell death. The genome wide screen identified transcriptional changes in multiple cell death related pathways that are indicative of a simultaneous activation of both degenerative and protective mechanisms. Quantitative PCR analyses of a subset of these genes in different neuronal populations of the basal ganglia revealed that some of the changes are specific for DA neurons, suggesting that these neurons are highly sensitive to rotenone. Our data provide insight into potentially defensive strategies of DA neurons against disease relevant insults.
url http://www.sciencedirect.com/science/article/pii/S0969996108002519
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