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1Circadian patterns of gene expression in the human brain and disruption in major depressive disorder
المؤلفون: Prabhakara V. Choudary, David M. Walsh, Fan Meng, Jack D. Barchas, Preston M. Cartagena, Simon J. Evans, Huda Akil, Blynn G. Bunney, Richard M. Myers, Edward G. Jones, Jun Li, William E. Bunney, Alan F. Schatzberg, Megan Hastings Hagenauer, Marquis P. Vawter, Stanley J. Watson
المصدر: Proceedings of the National Academy of Sciences. 110:9950-9955
مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Circadian clock, Biology, Circadian Clocks, Internal medicine, Basic Helix-Loop-Helix Transcription Factors, medicine, Humans, Circadian rhythm, Aged, Oligonucleotide Array Sequence Analysis, Homeodomain Proteins, Depressive Disorder, Major, Multidisciplinary, Suprachiasmatic nucleus, Gene Expression Profiling, ARNTL Transcription Factors, Brain, Period Circadian Proteins, Human brain, Middle Aged, Biological Sciences, Circadian Rhythm, CLOCK, ARNTL, Dorsolateral prefrontal cortex, medicine.anatomical_structure, Endocrinology, Nuclear Receptor Subfamily 1, Group D, Member 1, Female, Autopsy, Neuroscience
الوصف: A cardinal symptom of major depressive disorder (MDD) is the disruption of circadian patterns. However, to date, there is no direct evidence of circadian clock dysregulation in the brains of patients who have MDD. Circadian rhythmicity of gene expression has been observed in animals and peripheral human tissues, but its presence and variability in the human brain were difficult to characterize. Here, we applied time-of-death analysis to gene expression data from high-quality postmortem brains, examining 24-h cyclic patterns in six cortical and limbic regions of 55 subjects with no history of psychiatric or neurological illnesses (“controls”) and 34 patients with MDD. Our dataset covered ∼12,000 transcripts in the dorsolateral prefrontal cortex, anterior cingulate cortex, hippocampus, amygdala, nucleus accumbens, and cerebellum. Several hundred transcripts in each region showed 24-h cyclic patterns in controls, and >100 transcripts exhibited consistent rhythmicity and phase synchrony across regions. Among the top-ranked rhythmic genes were the canonical clock genes BMAL1(ARNTL), PER1-2-3, NR1D1(REV-ERBa), DBP, BHLHE40 (DEC1) , and BHLHE41(DEC2) . The phasing of known circadian genes was consistent with data derived from other diurnal mammals. Cyclic patterns were much weaker in the brains of patients with MDD due to shifted peak timing and potentially disrupted phase relationships between individual circadian genes. This transcriptome-wide analysis of the human brain demonstrates a rhythmic rise and fall of gene expression in regions outside of the suprachiasmatic nucleus in control subjects. The description of its breakdown in MDD suggests potentially important molecular targets for treatment of mood disorders.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4ed0be26897600b3e57a38e14f15decbTest
https://doi.org/10.1073/pnas.1305814110Test -
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المؤلفون: Edward G. Jones, D. M. Walsh, William E. Bunney, Fan Meng, Juan F. Lopez, Hiroaki Tomita, Simon J. Evans, Richard M. Myers, John D.H. Stead, Huda Akil, Robert C. Thompson, Jun Li, S.J. Watson, Marquis P. Vawter, Charles R. Neal, Prabhakara V. Choudary
المصدر: Proceedings of the National Academy of Sciences. 101:15506-15511
مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Serotonin reuptake inhibitor, In situ hybridization, Biology, Fibroblast growth factor, Polymerase Chain Reaction, behavioral disciplines and activities, Growth factor receptor, Internal medicine, mental disorders, Gene expression, medicine, Humans, In Situ Hybridization, Aged, Oligonucleotide Array Sequence Analysis, Aged, 80 and over, Depressive Disorder, Major, Multidisciplinary, Microarray analysis techniques, Biological Sciences, Middle Aged, medicine.disease, Fibroblast Growth Factors, Endocrinology, Mechanism of action, Major depressive disorder, Female, medicine.symptom, Selective Serotonin Reuptake Inhibitors
الوصف: In this report we describe findings that imply dysregulation of several fibroblast growth factor (FGF) system transcripts in frontal cortical regions of brains from human subjects with major depressive disorder (MDD). This altered gene expression was discovered by microarray analysis of frontal cortical tissue from MDD, bipolar, and nonpsychiatric control subjects and was verified by quantitative real-time PCR analysis and, importantly, in a separate cohort of MDD subjects. Furthermore, we show, through a separate analysis of specific serotonin reuptake inhibitor (SSRI)-treated and non-SSRI-treated MDD subjects that the observed changes in expression of FGF transcripts are not secondary to drug treatment. Rather, changes in specific FGF transcripts are attenuated by SSRIs and may thus be partially responsible for the mechanism of action of these drugs. We also make available the gene-expression profile of all of the other growth factors and growth factor receptors detected in these postmortem samples.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4e4a9c37bc37a9d0771e810395187cdaTest
https://doi.org/10.1073/pnas.0406788101Test