The family of short trans-acting antisense RNA transcripts known as the microRNAs regulate target mRNAs via eliciting mRNA degradation or arrested translation. MicroRNAs are important in regulating prenatal brain development, and almost certainly have functions within the mature brain as well. We hypothesize that microRNAs participate in the regulation of human mRNAs, including those that are involved in the pathophysiology of psychiatric disorders. Although postmortem human brain samples have proven to be a valuable and unique resource for studying biochemical abnormalities that occur in depression and major psychoses, no methods for reliably measuring microRNAs have yet been reported for postmortem brain. In order to study the possible role of microRNA pathways in human disease, we aim to: 1) Validate methods of microRNA microarrays for measuring known human microRNAs within postmortem human brain. 2) Compare microRNA expression in prefrontal cortex across two different cohorts of postmortem brain samples including normal controls and a set of matched depressed subjects. The purpose of this proposal is to set the stage for genome-wide analysis of all known human microRNAs in samples of postmortem brain. This is the necessary first step towards our eventual goals: to learn which mRNA targets and neural pathways are regulated by microRNAs, and to learn whether any specific microRNAs show differential expression in subjects with psychiatric disorders. Our proposed study will yield important information on the neurobiology of depression and may indicate possible novel sites for therapeutic interventions, which may eventually lead to better treatment and possibly prevention of depression. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH081099-02
Application #
7447431
Study Section
Special Emphasis Panel (ZRG1-BDCN-A (90))
Program Officer
Meinecke, Douglas L
Project Start
2007-06-14
Project End
2010-11-30
Budget Start
2008-06-01
Budget End
2010-11-30
Support Year
2
Fiscal Year
2008
Total Cost
$209,250
Indirect Cost
Name
University of Illinois at Chicago
Department
Psychiatry
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Ludwig, Birgit; Dwivedi, Yogesh (2018) The concept of violent suicide, its underlying trait and neurobiology: A critical perspective. Eur Neuropsychopharmacol 28:243-251
Wang, Qingzhong; Shelton, Richard C; Dwivedi, Yogesh (2018) Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis. J Affect Disord 225:422-428
Roy, Bhaskar; Wang, Qingzhong; Palkovits, Miklos et al. (2017) Altered miRNA expression network in locus coeruleus of depressed suicide subjects. Sci Rep 7:4387
Wang, Qingzhong; Timberlake 2nd, Matthew A; Prall, Kevin et al. (2017) The recent progress in animal models of depression. Prog Neuropsychopharmacol Biol Psychiatry 77:99-109
Roy, Bhaskar; Shelton, Richard C; Dwivedi, Yogesh (2017) DNA methylation and expression of stress related genes in PBMC of MDD patients with and without serious suicidal ideation. J Psychiatr Res 89:115-124
Roy, Bhaskar; Dwivedi, Yogesh (2017) Understanding epigenetic architecture of suicide neurobiology: A critical perspective. Neurosci Biobehav Rev 72:10-27
Roy, Bhaskar; Dunbar, Michael; Shelton, Richard C et al. (2017) Identification of MicroRNA-124-3p as a Putative Epigenetic Signature of Major Depressive Disorder. Neuropsychopharmacology 42:864-875
Ludwig, B; Dwivedi, Y (2016) Dissecting bipolar disorder complexity through epigenomic approach. Mol Psychiatry 21:1490-1498
Dwivedi, Yogesh (2016) Pathogenetic and therapeutic applications of microRNAs in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 64:341-8
Dwivedi, Y; Roy, B; Lugli, G et al. (2015) Chronic corticosterone-mediated dysregulation of microRNA network in prefrontal cortex of rats: relevance to depression pathophysiology. Transl Psychiatry 5:e682

Showing the most recent 10 out of 30 publications