The microRNA network is altered in anterior cingulate cortex of patients with unipolar and bipolar depression |
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| Affiliation: | 1. Molecular and Behavioral Neuroscience Institute, University of Michigan, 205 Zina Pitcher Pl, Ann Arbor, MI, 48109, USA;2. Neuroscience Graduate Program, University of Michigan, 4137 Undergraduate Science Building (USB), 204 Washtenaw Avenue, Ann Arbor, MI, 48109, USA;3. Neuroscience Program, Oberlin College, Science Center A261, 119 Woodland St., Oberlin, OH, 44074, USA;4. Pritzker Neuropsychiatric Disorders Research Consortium, USA;5. Department of Psychiatry and Behavioral Sciences, Stanford University, 401 Quarry Rd, Stanford, CA, 94305, USA;6. Department of Psychiatry, Weill Cornell Medical College, 525 East 68th Street, New York, NY, 10065, USA;7. Center for Neuroscience, University of California - Davis, 1544 Newton Court, Davis, CA, 95618, USA;8. Psychiatry and Human Behavior, University of California – Irvine, 101 The City Dr S, Orange, CA, 92868, USA;9. Hudson Alpha Institute for Biotechnology, 601 Genome Way Northwest, Huntsville, AL, 35806, USA;10. Department of Psychiatry, University of Michigan, 530 Church St, Ann Arbor, MI, 48109, USA;11. Department of Biological Chemistry, University of Michigan, 5301 MSRB III, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109, USA;1. Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California Los Angeles, 635 Charles E Young Drive S #225, Los Angeles, CA, 90095, USA;2. Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, 200 UCLA Medical Plaza #265, Los Angeles, CA, 90095, USA;1. Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil;2. Programa de Pós-graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil;3. Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900, Florianópolis, SC, Brazil;4. Curso de Farmácia, Universidade do Contestado, 89460-000, Canoinhas, SC, Brazil;1. Santa Lucia Foundation, Via del Fosso di Fiorano, 64-00143 Rome, Italy;2. Department of Psychology and Center “Daniel Bovet”, Sapienza University, Rome, Italy;3. Department of Applied Clinical Science and Biotechnology, University of L''Aquila, Coppito, Italy;4. Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer, New York, NY, USA;5. Department of Human Sciences, Libera Università Maria SS. Assunta, Borgo Sant''Angelo, 13-00193 Rome, Italy;6. Cell Biology and Neurobiology Institute – CNR, Via del Fosso di Fiorano, 64-00143 Rome, Italy;1. Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China;2. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China;3. Institution of Drug Clinical Trials, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China;1. Department of Psychiatry and Psychology, Second Military Medical University, Shanghai 200433, People''s Republic of China;2. Administrative Affairs Office, No.102 Hospital of Chinese People''s Liberation Army, Changzhou, Jiangsu 213003, People''s Republic of China;3. Department of Laboratory, No.102 Hospital of Chinese People''s Liberation Army, Changzhou, Jiangsu 213003, People''s Republic of China;4. Department of Rehabilitation, No.102 Hospital of Chinese People''s Liberation Army, Changzhou, Jiangsu 213003, People''s Republic of China;5. Department of Psychiatry, Suzhou Psychiatric Hospital, Suzhou 215008, Jiangsu, People''s Republic of China;6. GoPath Diagnostic Laboratory Co. Ltd, No. 801, Changwuzhong Road, Changzhou, Jiangsu 213164, People''s Republic of China;7. GoPath Laboratories LLC, 1351 Barclay Blvd, Buffalo Grove, IL 60089, USA;8. Prevention and Treatment Center for Psychological Diseases, No. 102 Hospital of Chinese People''s Liberation Army, North Peace Road 55, Changzhou 213003, Jiangsu, People''s Republic of China |
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| Abstract: | MicroRNAs (miRNAs) are small, non-coding RNAs acting as post-transcriptional regulators of gene expression. Though implicated in multiple CNS disorders, miRNAs have not been examined in any psychiatric disease state in anterior cingulate cortex (AnCg), a brain region centrally involved in regulating mood. We performed qPCR analyses of 29 miRNAs previously implicated in psychiatric illness (major depressive disorder (MDD), bipolar disorder (BP) and/or schizophrenia (SZ)) in AnCg of patients with MDD and BP versus controls. miR-132, miR-133a and miR-212 were initially identified as differentially expressed in BP, miR-184 in MDD and miR-34a in both MDD and BP (although none survived multiple correction testing and must be considered preliminary). In silico target prediction algorithms identified putative targets of differentially expressed miRNAs. Nuclear Co-Activator 1 (NCOA1), Nuclear Co-Repressor 2 (NCOR2) and Phosphodiesterase 4B (PDE4B) were selected based upon predicted targeting by miR-34a (with NCOR2 and PDE4B both targeted by miR-184) and published relevance to psychiatric illness. Luciferase assays identified PDE4B as a target of miR-34a and miR-184, while NCOA1 and NCOR2 were targeted by miR-34a and 184, respectively. qPCR analyses were performed to determine whether changes in miRNA levels correlated with mRNA levels of validated targets. NCOA1 showed an inverse correlation with miR-34a in BP, while NCOR2 demonstrated a positive correlation. In sum, this is the first study to demonstrate miRNA changes in AnCg in psychiatric illness and validate miR-34a as differentially expressed in CNS in MDD. These findings support a mechanistic role for miRNAs in the regulation of stress-responsive genes disrupted in psychiatric illness. |
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| Keywords: | microRNA Mood disorders Anterior cingulate cortex |
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