Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcriptome profiling of the human dorsal striatum in bipolar disorder

ABSTRACT: Bipolar disorder (BD) is a highly heritable and heterogeneous mental illness whose manifestations often include impulsive and risk-taking behavior. This particular phenotype suggests that abnormal striatal function could be involved in BD etiology, yet most transcriptomic studies of this disorder have concentrated on cortical brain regions. We report the first transcriptome profiling by RNA-Seq of the human dorsal striatum comparing bipolar and control subjects. Differential expression analysis and functional pathway enrichment analysis were performed to identify changes in gene expression that correlate with BD status. Further co-expression and enrichment analyses were performed to identify sets of correlated genes that show association to BD. Total RNA samples were isolated from 36 postmortem dorsal striatum subjects (18 bipolar and 18 control) and sequenced. One outlier sample was removed and 35 samples (18 bipolar and 17 control) were analyzed.

ORGANISM(S): Homo sapiens

SUBMITTER: Ronald Davis

PROVIDER: E-GEOD-80336 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Transcriptome sequencing implicates dorsal striatum-specific gene network, immune response and energy metabolism pathways in bipolar disorder.

Pacifico R R Davis R L RL

Molecular psychiatry 20160628 3

Bipolar disorder (BD) is a highly heritable and heterogeneous mental illness whose manifestations often include impulsive and risk-taking behavior. This particular phenotype suggests that abnormal striatal function could be involved in BD etiology, yet most transcriptomic studies of this disorder have concentrated on cortical brain regions. We believe we report the first transcriptome sequencing of the postmortem human dorsal striatum comparing bipolar (18) and control (17) subjects. Fourteen ge ...[more]

PMID: 27350034

Similar Datasets

Project description:Bipolar Disorder (BD) is a complex neuropsychiatric disorder that is characterized by intermittent episodes of mania and depression and, without treatment, 15% of patients commit suicide1. Hence, among all diseases, BD has been ranked by the WHO as a top disorder of morbidity and lost productivity2. Previous neuropathological studies have revealed a series of alterations in the brains of BD patients or animal models3, such as reduced glial cell number in the patient prefrontal cortex4, up-regulated activities of the PKA/PKC pathways5-7, and changes in dopamine/5-HT/glutamate neurotransmission systems8-11. However, the roles and causation of these changes in BD are too complex to exactly determine the pathology of the disease; none of the current BD animal models can recapitulate both the manic and depressive phenotypes or spontaneous cycling of BD simultaneously12,13. Furthermore, while some patients show remarkable improvement with lithium treatment, for yet unknown reasons, other patients are refractory to lithium treatment. Therefore, developing an accurate and powerful biological model has been a challenge for research into BD. The development of induced pluripotent stem cell (iPSC) technology has provided such a new approach. Here, we developed a human BD iPSC model and investigated the cellular phenotypes of hippocampal dentate gyrus neurons derived from the patient iPSCs. Using patch clamp recording, somatic Ca2+ imaging and RNA-seq techniques, we found that the neurons derived from BD patients exhibited hyperactive action potential (AP) firing, up-regulated expression of PKA/PKC/AP and mitochondria-related genes. Moreover, lithium selectively reversed these alterations in the neurons of patients who responded to lithium treatment. Therefore, hyper-excitability is one endophenotype of BD that is probably achieved through enhancement in the PKA/PKC and Na+ channel signaling systems, and our BD iPSC model can be used to develop new therapies and drugs aimed at clinical treatment of this disease. total RNAseq from neurons generated from BD patient-specific iPS cells

Dataset Information

Transcriptome profiling of the human dorsal striatum in bipolar disorder

Publications

Transcriptome sequencing implicates dorsal striatum-specific gene network, immune response and energy metabolism pathways in bipolar disorder.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure