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Brain Res. 2015 Aug 27;1618:111-21. doi: 10.1016/j.brainres.2015.05.021. Epub 2015 Jun 3.

Midbrain dopamine neurons in Parkinson's disease exhibit a dysregulated miRNA and target-gene network.

Author information

1
The Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, MA 02135, USA.
2
Life Technologies, Foster City, CA 94404, USA.
3
Department of Psychiatry, McLean Hospital, Harvard Medical School, MRC 223, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA.
4
Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02135, USA.
5
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.

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.

KEYWORDS:

Dopamine neurons; IPA; Laser capture microdissection; Parkinson׳s disease; miRNAs

PMID:
26047984
PMCID:
PMC4522231
DOI:
10.1016/j.brainres.2015.05.021
[Indexed for MEDLINE]
Free PMC Article

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