Association between the oral microbiome and brain resting state connectivity in schizophrenia.

Recent microbiome-brain axis findings have shown evidence of the modulation of microbiome community as an environmental mediator in brain function and psychiatric illness. This work is focused on the role of the microbiome in understanding a rarely investigated environmental involvement in schizophrenia (SZ), especially in relation to brain circuit dysfunction. We leveraged high throughput microbial 16s rRNA sequencing and functional neuroimaging techniques to enable the delineation of microbiome-brain network links in SZ.

Cross-continental environmental and genome-wide association study on children and adolescent anxiety and depression.

Anxiety and depression in children and adolescents warrant special attention as a public health concern given their devastating and long-term effects on development and mental health. Multiple factors, ranging from genetic vulnerabilities to environmental stressors, influence the risk for the disorders. This study aimed to understand how environmental factors and genomics affect children and adolescents anxiety and depression across three cohorts: Adolescent Brain and Cognitive Development Study (US, age of 9-10; N=11,875), Consortium on Vulnerability to Externalizing Disorders and Addictions (INDIA, age of 6-17; N=4,326) and IMAGEN (EUROPE, age of 14; N=1888).

Cold-Inducible RNA Binding Protein Impedes Breast Tumor Growth in the PyMT Murine Model for Breast Cancer.

RNA binding proteins (RBPs) post-transcriptionally regulate gene expression by associating with regulatory sequences in the untranslated regions of mRNAs. Cold-inducible RBP (CIRP) is a stress-induced RBP that was recently shown to modulate inflammation in response to cellular stress, where it increases or decreases pro-tumorigenic (proinflammatory) cytokines in different contexts. CIRP expression is altered in several cancers, including breast cancer, but the effects of CIRP on inflammation in breast cancer is not known.

Regulation of neuronal circHomer1 biogenesis by PKA/CREB/ERK-mediated pathways and effects of glutamate and dopamine receptor blockade.

There are currently only very few efficacious drug treatments for SCZ and BD, none of which can significantly ameliorate cognitive symptoms. Thus, further research is needed in elucidating molecular pathways linked to cognitive function and antipsychotic treatment. Circular RNAs (circRNAs) are stable brain-enriched non-coding RNAs, derived from the covalent back-splicing of precursor mRNA molecules.

Association between the oral microbiome and brain resting state connectivity in schizophrenia.

Recent microbiome-brain axis findings have shown evidence of the modulation of microbiome community as an environmental mediator in brain function and psychiatric illness. This work is focused on the role of the microbiome in understanding a rarely investigated environmental involvement in schizophrenia (SZ), especially in relation to brain circuit dysfunction. We leveraged high throughput microbial 16s rRNA sequencing and functional neuroimaging techniques to enable the delineation of microbiome-brain network links in SZ.

Repetitive spreading depolarization induces gene expression changes related to synaptic plasticity and neuroprotective pathways.

Spreading depolarization (SD) is a slowly propagating wave of profound depolarization that sweeps through cortical tissue. While much emphasis has been placed on the damaging consequences of SD, there is uncertainty surrounding the potential activation of beneficial pathways such as cell survival and plasticity. The present study used unbiased assessments of gene expression to evaluate that compensatory and repair mechanisms could be recruited following SD, regardless of the induction method, which prior to this work had not been assessed.

An approach for prioritizing candidate genes from RNA-seq using preclinical cocaine self-administration datasets as a test case.

RNA-sequencing (RNA-seq) technology has led to a surge of neuroscience research using animal models to probe the complex molecular mechanisms underlying brain function and behavior, including substance use disorders. However, findings from rodent studies often fail to be translated into clinical treatments. Here, we developed a novel pipeline for narrowing candidate genes from preclinical studies by translational potential and demonstrated its utility in 2 RNA-seq studies of rodent self-administration.

Cross-continental environmental and genome-wide association study on children and adolescent anxiety and depression.

Anxiety and depression in children and adolescents warrant special attention as a public health issue given their devastating and long-term effects on development and mental health. Multiple factors, ranging from genetic vulnerabilities to environmental stressors, influence the risk for the disorders. This study investigated the impact of environmental factors and genomics on anxiety and depression in children and adolescents across three cohorts: the Adolescent Brain and Cognitive Development Study (US), the Consortium on Vulnerability to Externalizing Disorders and Addictions (India), and IMAGEN (Europe).

Repetitive Spreading Depolarization induces gene expression changes related to synaptic plasticity and neuroprotective pathways.

Spreading depolarization (SD) is a slowly propagating wave of profound depolarization that sweeps through cortical tissue. While much emphasis has been placed on the damaging consequences of SD, there is uncertainty surrounding the potential activation of beneficial pathways such as cell survival and plasticity. The present study used unbiased assessments of gene expression to evaluate that compensatory and repair mechanisms could be recruited following SD, regardless of the induction method, which prior to this work had not been assessed.

Noncoding Regulatory RNAs: Isolation and Analysis of Neuronal Circular RNAs and MicroRNAs.

In addition to expressing a large number of protein-coding transcripts, including alternatively spliced isoforms of the same mRNAs, neurons express a large number of noncoding RNAs. These include microRNAs (miRNAs), circular RNAs (circRNAs), and other regulatory RNAs. The isolation and quantitative analyses of diverse types of RNAs in neurons are critical to understand not only the posttranscriptional mechanisms regulating mRNA levels and their translation but also the potential of several RNAs expressed in the same neurons to regulate these processes by generating networks of competing endogenous RNAs (ceRNAs).

Cross-continental environmental and genome-wide association study on children and adolescent anxiety and depression.

Anxiety and depression in children and adolescents warrant special attention as a public health issue given their devastating and long-term effects on development and mental health. Multiple factors, ranging from genetic vulnerabilities to environmental stressors, influence the risk for the disorders. This study aimed to understand how environmental factors and genomics affect children and adolescents anxiety and depression across three cohorts: Adolescent Brain and Cognitive Development Study (US, age of 9-10), Consortium on Vulnerability to Externalizing Disorders and Addictions (INDIA, age of 6-17) and IMAGEN (EUROPE, age of 14).

Clinical and cortical similarities identified between bipolar disorder I and schizophrenia: A multivariate approach.

Background: Structural neuroimaging studies have identified similarities in the brains of individuals diagnosed with schizophrenia (SZ) and bipolar I disorder (BP), with overlap in regions of gray matter (GM) deficits between the two disorders. Recent studies have also shown that the symptom phenotypes associated with SZ and BP may allow for a more precise categorization than the current diagnostic criteria. In this study, we sought to identify GM alterations that were unique to each disorder and whether those alterations were also related to unique symptom profiles.

Derivation and utility of schizophrenia polygenic risk associated multimodal MRI frontotemporal network.

Schizophrenia is a highly heritable psychiatric disorder characterized by widespread functional and structural brain abnormalities. However, previous association studies between MRI and polygenic risk were mostly ROI-based single modality analyses, rather than identifying brain-based multimodal predictive biomarkers. Based on schizophrenia polygenic risk scores (PRS) from healthy white people within the UK Biobank dataset (N = 22,459), we discovered a robust PRS-associated brain pattern with smaller gray matter volume and decreased functional activation in frontotemporal cortex, which distinguished schizophrenia from controls with >83% accuracy, and predicted cognition and symptoms across 4 independent schizophrenia cohorts.

KHSRP loss increases neuronal growth and synaptic transmission and alters memory consolidation through RNA stabilization.

The KH-type splicing regulatory protein (KHSRP) is an RNA-binding protein linked to decay of mRNAs with AU-rich elements. KHSRP was previously shown to destabilize Gap43 mRNA and decrease neurite growth in cultured embryonic neurons. Here, we have tested functions of KHSRP in vivo.

Intra-axonal translation of Khsrp mRNA slows axon regeneration by destabilizing localized mRNAs.

Axonally synthesized proteins support nerve regeneration through retrograde signaling and local growth mechanisms. RNA binding proteins (RBP) are needed for this and other aspects of post-transcriptional regulation of neuronal mRNAs, but only a limited number of axonal RBPs are known. We used targeted proteomics to profile RBPs in peripheral nerve axons.

A bidirectional competitive interaction between circHomer1 and Homer1b within the orbitofrontal cortex regulates reversal learning.

Although circular RNAs (circRNAs) are enriched in the brain, their relevance for brain function and psychiatric disorders is poorly understood. Here, we show that circHomer1 is inversely associated with relative HOMER1B mRNA isoform levels in both the orbitofrontal cortex (OFC) and stem-cell-derived neuronal cultures of subjects with psychiatric disorders. We further demonstrate that in vivo circHomer1 knockdown (KD) within the OFC can inhibit the synaptic expression of Homer1b mRNA.

The RNA-Binding Protein HuD Regulates Alternative Splicing and Alternative Polyadenylation in the Mouse Neocortex.

The neuronal Hu/ELAV-like proteins HuB, HuC and HuD are a class of RNA-binding proteins that are crucial for proper development and maintenance of the nervous system. These proteins bind to AU-rich elements (AREs) in the untranslated regions (3'-UTRs) of target mRNAs regulating mRNA stability, transport and translation. In addition to these cytoplasmic functions, Hu proteins have been implicated in alternative splicing and alternative polyadenylation in the nucleus.

microRNA regulation related to the protective effects of environmental enrichment against cocaine-seeking behavior.

Background: MicroRNAs (miRNAs) are "master post-transcriptional regulators" of gene expression. Here we investigate miRNAs involved in the incentive motivation for cocaine elicited by exposure to cocaine-associated cues.

Methods: We conducted NanoString nCounter analyses of microRNA expression in the nucleus accumbens shell of male rats that had been tested for cue reactivity in a previous study.

HuD regulates SOD1 expression during oxidative stress in differentiated neuroblastoma cells and sporadic ALS motor cortex.

The neuronal RNA-binding protein (RBP) HuD plays an important role in brain development, synaptic plasticity and neurodegenerative diseases such as Parkinson's (PD) and Alzheimer's (AD). Bioinformatics analysis of the human SOD1 mRNA 3' untranslated region (3'UTR) demonstrated the presence of HuD binding adenine-uridine (AU)-rich instability-conferring elements (AREs). Using differentiated SH-SY5Y cells along with brain tissues from sporadic amyotrophic lateral sclerosis (sALS) patients, we assessed HuD-dependent regulation of SOD1 mRNA.

Network modules linking expression and methylation in prefrontal cortex of schizophrenia.

Tremendous work has demonstrated the critical roles of genetics, epigenetics as well as their interplay in brain transcriptional regulations in the pathology of schizophrenia (SZ). There is great success currently in the dissection of the genetic components underlying risk-conferring transcriptomic networks. However, the study of regulating effect of epigenetics in the etiopathogenesis of SZ still faces many challenges.

HuD Binds to and Regulates Circular RNAs Derived From Neuronal Development- and Synaptic Plasticity-Associated Genes.

The RNA-binding protein (RBP) HuD is involved in neuronal differentiation, regeneration, synaptic plasticity and learning and memory. RBPs not only bind to mRNAs but also interact with several types of RNAs including circular RNAs (circRNAs), a class of non-coding RNAs generated by pre-mRNA back-splicing. This study explored whether HuD could regulate the expression of neuronal circRNAs.