title: Midbrain dopamine neurons in Parkinson's disease exhibit a dysregulated miRNA and target-gene network.
abstract: The degeneration of substantia nigra (SN) dopamine (DA) neurons in sporadic Parkinson׳s disease (PD) is characterized by disturbed gene expression networks. Micro(mi)RNAs are post-transcriptional regulators of gene expression and we recently provided evidence that these molecules may play a functional role in the pathogenesis of PD. Here, we document a comprehensive analysis of miRNAs in SN DA neurons and PD, including sex differences. Our data show that miRNAs are dysregulated in disease-affected neurons and differentially expressed between male and female samples with a trend of more up-regulated miRNAs in males and more down-regulated miRNAs in females. Unbiased Ingenuity Pathway Analysis (IPA) revealed a network of miRNA/target-gene associations that is consistent with dysfunctional gene and signaling pathways in PD pathology. Our study provides evidence for a general association of miRNAs with the cellular function and identity of SN DA neurons, and with deregulated gene expression networks and signaling pathways related to PD pathogenesis that may be sex-specific.
authors.affiliation: The Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, MA 02135, USA.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Briggs
authors.affiliation: Life Technologies, Foster City, CA 94404, USA.
authors.forename: Yulei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Life Technologies, Foster City, CA 94404, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kong
authors.affiliation: Department of Psychiatry, McLean Hospital, Harvard Medical School, MRC 223, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA.
authors.forename: Tsung-Ung W
authors.initials: TU
authors.lastname: Woo
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02135, USA.
authors.forename: Lakshmanan K
authors.initials: LK
authors.lastname: Iyer
authors.affiliation: Department of Psychiatry, McLean Hospital, Harvard Medical School, MRC 223, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. Electronic address: ksonntag@mclean.harvard.edu.
authors.forename: Kai C
authors.initials: KC
authors.lastname: Sonntag
mesh_terms: D059290:Dopaminergic Neurons / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010300:Parkinson Disease / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs
keywords: Dopamine neurons; IPA; Laser capture microdissection; Parkinson׳s disease; miRNAs