scholarly journals Differential Expression of NPAS4 in the Dorsolateral Prefrontal Cortex Following Acute Opioid Intoxication

2020 ◽  
Author(s):  
David W. Sosnowski ◽  
Andrew E. Jaffe ◽  
Ran Tao ◽  
Amy Deep-Soboslay ◽  
Joel E. Kleinman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Differential Expression ◽  
Dorsolateral Prefrontal Cortex ◽  
Opioid Abuse ◽  
Differentially Expressed ◽  
Opioid Use ◽  
Opioid Intoxication ◽  
Dorsolateral Prefrontal ◽  
Control Samples

AbstractBackground and AimsThe physical, emotional, and social impacts of opioid abuse are well known; although preclinical models reveal the neurobiological pathways altered through opioid abuse, comprehensive assessments of gene expression in human brain samples are lacking. The goals of the present study were to compare gene expression in the prefrontal cortex between brain samples of individuals who died of acute opioid intoxication and group-matched controls, and to test if differential gene expression was enriched in gene sets related to opioid use.DesignCross-sectional study using human brains donated to the Lieber Institute for Brain Development. Study groups included 72 brain samples from individuals who died of acute opioid intoxication, 53 group-matched psychiatric control samples, and 28 group-matched normal control samples.SettingMaryland, USA.ParticipantsPostmortem tissue samples of the dorsolateral prefrontal cortex from 153 deceased individuals (Mage = 35.42, SD = 9.43 years; 62% male; 77% White).MeasurementsWhole transcriptome RNA sequencing was used to generate exon counts, and differential expression was tested using limma-voom. Analyses controlled for relevant sociodemographic characteristics, technical covariates, and cryptic relatedness and batch effects using quality surrogate variable analysis. Gene set enrichment analyses (GSEA) also were conducted.FindingsSixteen genes were differentially expressed (i.e., FDR-corrected p < .10) in opioid samples compared to control samples. The top differentially expressed gene, NPAS4 (FDR adjusted p = .005), was downregulated in opioid samples and has previously been implicated in cocaine use. Enrichment analyses did not provide evidence for enrichment in pathways obviously related to opioid use.ConclusionsNPAS4 is differentially expressed in the prefrontal cortex of subjects that died of an opioid overdose, providing evidence for another gene with functional relevance to opioid use and overdose.

scholarly journals DDX19B is differentially expressed in the brains of patients with psychotic disorders.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Microarray Data ◽  
Schizoaffective Disorder ◽  
Dorsolateral Prefrontal Cortex ◽  
Psychotic Disorders ◽  
Differentially Expressed ◽  
Dorsolateral Prefrontal ◽  
Significant Gene

We used public and published microarray data (1, 2) to identify the most significant gene expression changes in the brains of patients with psychotic disorders. We DDX19B as differentially expressed in the dorsolateral prefrontal cortex of patients with schizophrenia and schizoaffective disorder. In neurons of the dorsolateral prefrontal cortex from patients with psychotic disorders, DDX19B expression was significantly decreased.

scholarly journals Peroxiredoxin 5 (PRDX5) is differentially expressed in the brains of patients with psychotic disorders.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Microarray Data ◽  
Schizoaffective Disorder ◽  
Dorsolateral Prefrontal Cortex ◽  
Psychotic Disorders ◽  
Differentially Expressed ◽  
Dorsolateral Prefrontal ◽  
Significant Gene ◽  
The Brain

We used public and published microarray data (1, 2) to identify the most significant gene expression changes in the brains of patients with psychotic disorders. We identified PRDX53 as differentially expressed in the dorsolateral prefrontal cortex of patients with schizophrenia as well as in the parvalbumin-positive layer 3 neurons of the dorsolateral prefrontal cortex of patients with schizophrenia and schizoaffective disorder. The brain tissues of patients with psychotic disorders expressed significantly lower levels of PRDX5 than that of non-affected control subjects. PRDX5 may be relevant to the biology of schizophrenia and related psychotic disorders.

scholarly journals Phospholipase C beta2 (PLCB2) is differentially expressed in the dorsolateral prefrontal cortex of patients with psychotic disorders.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Phospholipase C ◽  
Dorsolateral Prefrontal Cortex ◽  
Psychotic Disorders ◽  
Differentially Expressed ◽  
Dorsolateral Prefrontal ◽  
Microarray Datasets ◽  
And Control ◽  
Psychotic Bipolar Disorder

We mined two microarray datasets (published or public) (1, 2) to identify the most significant changes in gene expression in the brains of patients with psychotic disorders. We found that isoform 2 of phospholipase C beta (PLCB2) was among the genes most differentially expressed in the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia and psychotic bipolar disorder (1). In a separate dataset (2), PLCB2 was again among the genes whose expression changed most significantly when comparing parvalbumin-positive layer 3 neurons from the DLPFC between patients with schizophrenia and schizoaffective disorder and control subjects. Multiple studies have documented dysregulated PLCB1 expression in the brains of patients with schizophrenia, including in the dorsolateral prefrontal cortex (3-6). These data suggest that PLCB2 expression may also be perturbed in the brains of patients with psychotic disorders.

scholarly journals NDUFV1 is differentially expressed in the brains of patients with psychotic disorders.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Microarray Data ◽  
Schizoaffective Disorder ◽  
Dorsolateral Prefrontal Cortex ◽  
Psychotic Disorders ◽  
Differentially Expressed ◽  
Dorsolateral Prefrontal ◽  
Significant Gene

We used public and published microarray data (1, 2) to identify the most significant gene expression changes in the brains of patients with psychotic disorders. We identified NDUFV1 as differentially expressed in the dorsolateral prefrontal cortex of patients with schizophrenia and schizoaffective disorder. In neurons of the dorsolateral prefrontal cortex, NDUFV1 was expressed at significantly lower levels in patients with psychotic disorders.

scholarly journals RBMXL1 is differentially expressed in the brains of patients with psychotic disorders.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Microarray Data ◽  
Schizoaffective Disorder ◽  
Dorsolateral Prefrontal Cortex ◽  
Psychotic Disorders ◽  
Differentially Expressed ◽  
Dorsolateral Prefrontal ◽  
Significant Gene

We used public and published microarray data (1, 2) to identify the most significant gene expression changes in the brains of patients with psychotic disorders. We identified RBMXL1 as differentially expressed in the dorsolateral prefrontal cortex of patients with schizophrenia and schizoaffective disorder. In neurons of the dorsolateral prefrontal cortex, RBMXL1 was expressed at significantly lower levels in patients with psychotic disorders.

scholarly journals PAX8 is differentially expressed in the brains of patients with psychotic disorders.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Prefrontal Cortex ◽  
Microarray Data ◽  
Schizoaffective Disorder ◽  
Dorsolateral Prefrontal Cortex ◽  
Psychotic Disorders ◽  
Differentially Expressed ◽  
Dorsolateral Prefrontal ◽  
Significant Gene

We used public and published microarray data (1, 2) to identify the most significant gene expression changes in the brains of patients with psychotic disorders. We identified the paired box-containing transcription factor PAX8 as differentially expressed in the dorsolateral prefrontal cortex of patients with schizophrenia and schizoaffective disorder. In neurons of the dorsolateral prefrontal cortex, PAX8 was expressed at significantly higher levels in patients with psychotic disorders.

scholarly journals NTRK2 is differentially expressed in the brains of patients with psychotic disorders.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Bipolar Disorder ◽  
Prefrontal Cortex ◽  
Microarray Data ◽  
Dorsolateral Prefrontal Cortex ◽  
Psychotic Disorders ◽  
Differentially Expressed ◽  
Dorsolateral Prefrontal ◽  
Significant Gene ◽  
Psychotic Bipolar Disorder

We used published microarray data (1, 2) to identify the most significant gene expression changes in the brains of patients with psychotic disorders. We identified NTRK2 as differentially expressed in the dorsolateral prefrontal cortex of patients with schizophrenia as well as in the dorsolateral prefrontal cortex of patients with schizophrenia and psychotic bipolar disorder. NTRK2 expression was significantly higher in the dorsolateral prefrontal cortex of patients with psychotic disorders.

scholarly journals RNase L is differentially expressed in the brains of patients with psychotic disorders.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Microarray Data ◽  
Dorsolateral Prefrontal Cortex ◽  
Psychotic Disorders ◽  
Differentially Expressed ◽  
Rnase L ◽  
Gene Encoding ◽  
Dorsolateral Prefrontal ◽  
Significant Gene

We used public and published microarray data (1, 2) to identify the most significant gene expression changes in the brains of patients with psychotic disorders. We identified the gene encoding the endoribonuclease RNase L as differentially expressed in the dorsolateral prefrontal cortex of patients with schizophrenia and schizoaffective disorder. In neurons of the dorsolateral prefrontal cortex, RNase L was expressed at significantly lower levels in patients with psychotic disorders.

scholarly journals Molecular pathology associated with altered synaptic transcriptome in the dorsolateral prefrontal cortex of depressed subjects

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuta Yoshino ◽  
Bhaskar Roy ◽  
Nilesh Kumar ◽  
M. Shahid Mukhtar ◽  
Yogesh Dwivedi
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Gene Network ◽  
Nervous System Development ◽  
Network Analyses ◽  
Dorsolateral Prefrontal ◽  
Total Fraction ◽  
Transcriptomic Changes

AbstractDisrupted synaptic plasticity is the hallmark of major depressive disorder (MDD), with accompanying changes at the molecular and cellular levels. Often, the maladaptive molecular changes at the synapse are the result of global transcriptional reprogramming dictated by activity-dependent synaptic modulation. Thus far, no study has directly studied the transcriptome-wide expression changes locally at the synapse in MDD brain. Here, we have examined altered synaptic transcriptomics and their functional relevance in MDD with a focus on the dorsolateral prefrontal cortex (dlPFC). RNA was isolated from total fraction and purified synaptosomes of dlPFC from well-matched 15 non-psychiatric controls and 15 MDD subjects. Transcriptomic changes in synaptic and total fractions were detected by next-generation RNA-sequencing (NGS) and analyzed independently. The ratio of synaptic/total fraction was estimated to evaluate a shift in gene expression ratio in MDD subjects. Bioinformatics and network analyses were used to determine the biological relevance of transcriptomic changes in both total and synaptic fractions based on gene–gene network, gene ontology (GO), and pathway prediction algorithms. A total of 14,005 genes were detected in total fraction. A total of 104 genes were differentially regulated (73 upregulated and 31 downregulated) in MDD group based on 1.3-fold change threshold and p < 0.05 criteria. In synaptosomes, out of 13,236 detectable genes, 234 were upregulated and 60 were downregulated (>1.3-fold, p < 0.05). Several of these altered genes were validated independently by a quantitative polymerase chain reaction (qPCR). GO revealed an association with immune system processes and cell death. Moreover, a cluster of genes belonged to the nervous system development, and psychological disorders were discovered using gene–gene network analysis. The ratio of synaptic/total fraction showed a shift in expression of 119 genes in MDD subjects, which were primarily associated with neuroinflammation, interleukin signaling, and cell death. Our results suggest not only large-scale gene expression changes in synaptosomes, but also a shift in the expression of genes from total to synaptic fractions of dlPFC of MDD subjects with their potential role in immunomodulation and cell death. Our findings provide new insights into the understanding of transcriptomic regulation at the synapse and their possible role in MDD pathogenesis.

scholarly journals Publisher Correction: Transcriptome-scale spatial gene expression in the human dorsolateral prefrontal cortex

2021 ◽  
Author(s):  
Kristen R. Maynard ◽  
Leonardo Collado-Torres ◽  
Lukas M. Weber ◽  
Cedric Uytingco ◽  
Brianna K. Barry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Dorsolateral Prefrontal
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