Gene expression analysis in N‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine mice model of Parkinson's disease using cDNA microarray: effect of R‐apomorphine

To establish the possible roles of oxidative stress, inflammatory processes and other unknown mechanisms in neurodegeneration, we investigated brain gene alterations in N‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mice model of Parkinson's disease using Atlas mouse cDNA expression array membrane. The expression of 51 different genes involved in oxidative stress, inflammation, glutamate and neurotrophic factors pathways as well as in still undefined processes, such as cell cycle regulators and signal transduction molecules, was differentially affected by the treatment. The present study indicates the involvement of an additional cascade of events that might act in parallel to oxidative stress and inflammation to converge eventually into a common pathway leading to neurodegeneration. The attenuation of these gene changes by R‐apomorphine, an iron chelator‐radical scavenger drug, supports our previous findings in vivo where R‐apomorphine was neuroprotective.

[1]  Ted M. Dawson,et al.  Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease , 1999, Nature Medicine.

[2]  S. Mandel,et al.  The Pivotal Role of Iron in NF‐κB Activation and Nigrostriatal Dopaminergic Neurodegeneration: Prospects for Neuroprotection in Parkinson's Disease with Iron Chelators , 1999, Annals of the New York Academy of Sciences.

[3]  U. Mansmann,et al.  Differential gene expression in colon carcinoma cells and tissues detected with a cDNA array , 1999, International journal of cancer.

[4]  P. Mecocci,et al.  Oxidative damage to mitochondrial DNA in Huntington's disease parietal cortex , 1999, Neuroscience Letters.

[5]  C. K. Lee,et al.  Gene expression profile of aging and its retardation by caloric restriction. , 1999, Science.

[6]  D. Nebert,et al.  Tissue- and cell type-specific expression of cytochrome P450 1A1 and cytochrome P450 1A2 mRNA in the mouse localized in situ hybridization. , 1999, Biochemical pharmacology.

[7]  S. Mandel,et al.  Apomorphine protects against MPTP‐induced neurotoxicity in mice , 1999, Movement disorders : official journal of the Movement Disorder Society.

[8]  R. Djaldetti,et al.  IL-1β, IL-2, IL-6 and TNF-α production by peripheral blood mononuclear cells from patients with Parkinson's disease , 1999 .

[9]  Jin Hong Liu,et al.  Functional association of TGF-β receptor II with cyclin B , 1999, Oncogene.

[10]  A. Ashworth,et al.  Structure and chromosomal mapping of the TNF-alpha inducible endothelial protein 1 (Edp1) gene in the mouse. , 1998, Biochimica et biophysica acta.

[11]  P. Brown,et al.  Drug target validation and identification of secondary drug target effects using DNA microarrays , 1998, Nature Medicine.

[12]  R. Klausner,et al.  Cell‐cycle arrest and inhibition of G1 cyclin translation by iron in AFT1‐1up yeast , 1998, The EMBO journal.

[13]  Zhiming Zhang,et al.  Neuroprotective and neurorestorative properties of GDNF , 1998, Annals of neurology.

[14]  S H Kim,et al.  Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. , 1998, Science.

[15]  S. Hersch,et al.  A Human HAP1 Homologue , 1998, The Journal of Biological Chemistry.

[16]  I. Nakano,et al.  Effects of repeated systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mice on interleukin-1β and nerve growth factor in the striatum , 1998, Neuroscience Letters.

[17]  S. Gullans,et al.  Characterization of the Hsp110/SSE gene family response to hyperosmolality and other stresses. , 1998, American journal of physiology. Renal physiology.

[18]  S. Gullans,et al.  Characterization of the Hsp110/SSE gene family response to hyperosmolality and other stresses. , 1998, The American journal of physiology.

[19]  P. Jenner,et al.  P450 enzymes and Parkinson's disease: The story so far , 1998, Movement disorders : official journal of the Movement Disorder Society.

[20]  M. Youdim,et al.  Apomorphine enantiomers protect cultured pheochromocytoma (PC12) cells from oxidative stress induced by H2O2 and 6‐Hydroxydopamine , 1998, Movement disorders : official journal of the Movement Disorder Society.

[21]  Y Agid,et al.  Nuclear translocation of NF-kappaB is increased in dopaminergic neurons of patients with parkinson disease. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[22]  G. Brittenham,et al.  Role of iron in NF-kappa B activation and cytokine gene expression by rat hepatic macrophages. , 1997, The American journal of physiology.

[23]  R. W. Davis,et al.  Discovery and analysis of inflammatory disease-related genes using cDNA microarrays. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[24]  H. Yoshida,et al.  Low micromolar levels of hydrogen peroxide and proteasome inhibitors induce the 60-kDa A170 stress protein in murine peritoneal macrophages. , 1997, Biochemical and biophysical research communications.

[25]  M. Shibutani,et al.  Down-regulation of cyclin F levels during nerve growth factor-induced differentiation of PC12 cells. , 1996, Experimental cell research.

[26]  M. Youdim,et al.  Apomorphine is a highly potent free radical scavenger in rat brain mitochondrial fraction. , 1996, European journal of pharmacology.

[27]  T. Nagatsu,et al.  Interleukin (IL)-1β, IL-2, IL-4, IL-6 and transforming growth factor-α levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson's disease , 1996, Neuroscience Letters.

[28]  J. Lile,et al.  GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. , 1993, Science.

[29]  P. Baeuerle,et al.  Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF‐kappa B transcription factor and HIV‐1. , 1991, The EMBO journal.

[30]  N. Neff,et al.  Epidermal Growth Factor Enhances Striatal Dopaminergic Parameters in the 1‐Methyl‐4‐Phenyl‐l, 2, 3, 6‐Tetrahydropyridine‐Treated Mouse , 1991, Journal of neurochemistry.

[31]  Z. Rossetti,et al.  The non-competitive NMDA-receptor antagonist MK-801 prevents the massive release of glutamate and aspartate from rat striatum induced by 1-methyl-4-phenylpyridinium (MPP+) , 1990, Neuroscience Letters.

[32]  J. Garthwaite,et al.  NMDA receptor activation induces nitric oxide synthesis from arginine in rat brain slices. , 1989, European journal of pharmacology.

[33]  J. Fujitake,et al.  Immunohistochemical evaluation of the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on dopaminergic nigrostriatal neurons of young adult mice using dopamine and tyrosine hydroxylase antibodies , 1988, Neuroscience Letters.

[34]  INTERNATIONAL SOCIETY FOR NEUROCHEMISTRY , 1976 .

[35]  K. Jellinger,et al.  Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. , 1973, Journal of the neurological sciences.

[36]  A. Bowie,et al.  Oxidative stress and nuclear factor-kappaB activation: a reassessment of the evidence in the light of recent discoveries. , 2000, Biochemical pharmacology.

[37]  P. Goodfellow,et al.  DNA microarrays in drug discovery and development , 1999, Nature Genetics.

[38]  L. Penland,et al.  Use of a cDNA microarray to analyse gene expression patterns in human cancer , 1996, Nature Genetics.

[39]  C. Olanow,et al.  Neurodegeneration and Neuroprotection in Parkinson's Disease , 1996 .

[40]  S. Wrighton,et al.  The human hepatic cytochromes P450 involved in drug metabolism. , 1992, Critical reviews in toxicology.

[41]  K. Jellinger,et al.  Brain iron and ferritin in Parkinson's and Alzheimer's diseases , 1990, Journal of neural transmission. Parkinson's disease and dementia section.