Dysregulation of Gene Expression in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Lesioned Mouse Substantia Nigra
Renee M. Miller,Linda M. Callahan,Cindy Casaceli,Linlin Chen,Gretchen L. Kiser,Buena Chui,Tamma Kaysser-Kranich,Timothy J Sendera,Chockalingam Palaniappan,Howard J. Federoff +9 more
TLDR
Microarray analysis and integrative data mining were used to uncover pathways implicated in the progression of changes in dopaminergic neurons after MPTP administration and disclosed dysregulation of genes in three main areas related to neuronal function.Abstract:
Parkinson's disease pathogenesis proceeds through several phases, culminating in the loss of dopaminergic neurons of the substantia nigra (SN). Although the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of oxidative SN injury is frequently used to study degeneration of dopaminergic neurons in mice and non-human primates, an understanding of the temporal sequence of molecular events from inhibition of mitochondrial complex 1 to neuronal cell death is limited. Here, microarray analysis and integrative data mining were used to uncover pathways implicated in the progression of changes in dopaminergic neurons after MPTP administration. This approach enabled the identification of small, yet consistently significant, changes in gene expression within the SN of MPTP-treated animals. Such an analysis disclosed dysregulation of genes in three main areas related to neuronal function: cytoskeletal stability and maintenance, synaptic integrity, and cell cycle and apoptosis. The discovery and validation of these alterations provide molecular evidence for an evolving cascade of injury, dysfunction, and cell death.read more
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The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements
Leming Shi,Laura H. Reid,Wendell D. Jones,Richard Shippy,Janet A. Warrington,Shawn C. Baker,Patrick J. Collins,Francoise de Longueville,Ernest S. Kawasaki,Kathleen Y. Lee,Yuling Luo,Yongming Andrew Sun,James C. Willey,Robert Setterquist,Gavin M. Fischer,Weida Tong,Yvonne P. Dragan,David J. Dix,Felix W. Frueh,Federico Goodsaid,Damir Herman,Roderick V. Jensen,Charles D. Johnson,Edward K. Lobenhofer,Raj K. Puri,Uwe Scherf,Jean Thierry-Mieg,Charles Wang,Michael A Wilson,Paul K. Wolber,Lu Zhang,William Slikker,Shashi Amur,Wenjun Bao,Catalin Barbacioru,Anne Bergstrom Lucas,Vincent Bertholet,Cecilie Boysen,Bud Bromley,Donna Brown,Alan Brunner,Roger D. Canales,Xiaoxi Megan Cao,Thomas A. Cebula,James J. Chen,Jing Cheng,Tzu Ming Chu,Eugene Chudin,John F. Corson,J. Christopher Corton,Lisa J. Croner,Christopher Davies,Timothy Davison,Glenda C. Delenstarr,Xutao Deng,David Dorris,Aron Charles Eklund,Xiaohui Fan,Hong Fang,Stephanie Fulmer-Smentek,James C. Fuscoe,Kathryn Gallagher,Weigong Ge,Lei Guo,Xu Guo,Janet Hager,Paul K. Haje,Jing Han,Tao Han,Heather Harbottle,Stephen C. Harris,Eli Hatchwell,Craig A. Hauser,Susan D. Hester,Huixiao Hong,Patrick Hurban,Scott A. Jackson,Hanlee P. Ji,Charles R. Knight,Winston Patrick Kuo,J. Eugene LeClerc,Shawn Levy,Quan Zhen Li,Chunmei Liu,Ying Liu,Michael Lombardi,Yunqing Ma,Scott R. Magnuson,Botoul Maqsodi,Timothy K. McDaniel,Nan Mei,Ola Myklebost,Baitang Ning,Natalia Novoradovskaya,Michael S. Orr,Terry Osborn,Adam Papallo,Tucker A. Patterson,Roger Perkins,Elizabeth Herness Peters,Ron L. Peterson,Kenneth L. Philips,P. Scott Pine,Lajos Pusztai,Feng Qian,Hongzu Ren,Mitch Rosen,Barry A. Rosenzweig,Raymond R. Samaha,Mark Schena,Gary P. Schroth,Svetlana Shchegrova,Dave D. Smith,Frank Staedtler,Zhenqiang Su,Hongmei Sun,Zoltan Szallasi,Zivana Tezak,Danielle Thierry-Mieg,Karol L. Thompson,Irina Tikhonova,Yaron Turpaz,Beena Vallanat,Christophe Van,Stephen J. Walker,Sue Jane Wang,Yonghong Wang,Russell D. Wolfinger,Alexander Wong,Jie Wu,Chunlin Xiao,Qian Xie,Jun Xu,Wen Yang,Liang Zhang,Sheng Zhong,Yaping Zong +136 more
TL;DR: This study describes the experimental design and probe mapping efforts behind the MicroArray Quality Control project and shows intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed.
Journal ArticleDOI
Synuclein activates microglia in a model of Parkinson’s Disease
Xiaomin Su,Kathleen A. Maguire-Zeiss,Rita Giuliano,Landa Prifti,Karthik Venkatesh,Howard J. Federoff +5 more
TL;DR: The data suggest an early role for SYN and inflammation in PD pathogenesis, and evidence that the CD36 scavenger receptor and downstream kinases are involved in SYN-mediated microglial activation is provided.
Journal ArticleDOI
The balance of reproducibility, sensitivity, and specificity of lists of differentially expressed genes in microarray studies
Leming Shi,Wendell D. Jones,Roderick V. Jensen,Stephen C. Harris,Roger Perkins,Federico Goodsaid,Lei Guo,Lisa J. Croner,Cecilie Boysen,Hong Fang,Feng Qian,Shashi Amur,Wenjun Bao,Catalin Barbacioru,Vincent Bertholet,Xiaoxi Megan Cao,Tzu Ming Chu,Patrick J. Collins,Xiaohui Fan,Xiaohui Fan,Felix W. Frueh,James C. Fuscoe,Xu Guo,Jing Han,Damir Herman,Huixiao Hong,Ernest S. Kawasaki,Quan Zhen Li,Yuling Luo,Yunqing Ma,Nan Mei,Ron L. Peterson,Raj K. Puri,Richard Shippy,Zhenqiang Su,Yongming Andrew Sun,Hongmei Sun,Brett T. Thorn,Yaron Turpaz,Charles Wang,Sue Jane Wang,Janet A. Warrington,James C. Willey,Jie Wu,Qian Xie,Liang Zhang,Lu Zhang,Sheng Zhong,Russell D. Wolfinger,Weida Tong +49 more
TL;DR: The results provide practical guidance to choose the appropriate FC and P-value cutoffs when selecting a given number of DEGs and recommend the use of FC-ranking plus a non-stringent P cutoff as a straightforward and baseline practice in order to generate more reproducible DEG lists.
Journal ArticleDOI
Rat toxicogenomic study reveals analytical consistency across microarray platforms
Lei Guo,Edward K. Lobenhofer,Charles Wang,Richard Shippy,Stephen C. Harris,Lu Zhang,Nan Mei,Tao Chen,Damir Herman,Federico Goodsaid,Patrick Hurban,K. L. Phillips,Jun Xu,Xutao Deng,Yongming Andrew Sun,Weida Tong,Yvonne P. Dragan,Leming Shi +17 more
TL;DR: The real-world toxicogenomic data set reported here showed high concordance in intersite and cross-platform comparisons and gene lists generated by fold-change ranking were more reproducible than those obtained by t-test P value or Significance Analysis of Microarrays.
Journal ArticleDOI
Gene expression profiling of substantia nigra dopamine neurons: further insights into Parkinson's disease pathology
Filip Simunovic,Ming Yi,Yulei Wang,Laurel Macey,Lauren Brown,Anna M. Krichevsky,Susan L. Andersen,Robert M. Stephens,Francine M. Benes,Kai C. Sonntag +9 more
TL;DR: Laser microdissection is used to isolate single DA neurons from the substantia nigra pars compacta of controls and subjects with idiopathic Parkinson's disease matched for age and postmortem interval followed by microarrays to analyse gene expression profiling, which provide a 'molecular fingerprint identity' of late-stage Parkinson's Disease DA neurons that will advance understanding of the molecular pathology of this disease.
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