scholarly journals Molecular characterization of the stress network in the human brain

2019 ◽  
Author(s):  
Mandy Meijer ◽  
Arlin Keo ◽  
Judith M.C. van Leeuwen ◽  
Oleh Dzyubachyk ◽  
Onno C. Meijer ◽  
...  
Keyword(s):  
Human Brain ◽  
Psychiatric Disorders ◽  
Stress Reactivity ◽  
High Stress ◽  
Brain Regions ◽  
Stress Sensitivity ◽  
Brain Atlas ◽  
Neuronal Populations ◽  
Human Stress ◽  
Corticosteroid Receptor

ABSTRACTThe biological mechanisms underlying inter-individual differences in human stress reactivity remain poorly understood. We aimed to identify the molecular underpinning of neural stress sensitivity. Linking mRNA expression data from the Allen Human Brain Atlas to task-based fMRI revealed 201 differentially expressed genes in cortex-specific brain regions differentially activated by stress in individuals with low or high stress sensitivity. These genes are associated with stress-related psychiatric disorders (e.g. schizophrenia and anxiety) and include markers for specific neuronal populations (e.g.ADCYAP1, GABRB1, SSTR1, andTNFRSF12A), neurotransmitter receptors (e.g.GRIN3A, SSTR1, GABRB1, andHTR1E), and signaling factors that interact with the corticosteroid receptor and hypothalamic-pituitary-adrenal axis (e.g. ADCYAP1,IGSF11, and PKIA). Overall, the identified genes potentially underlie altered stress reactivity in individuals at risk for psychiatric disorders and play a role in mounting an adaptive stress response, making them potentially druggable targets for stress-related diseases.

scholarly journals NIMG-13. GENETIC, CELLULAR, AND CONNECTOMIC CHARACTERIZATION OF THE ADULT HUMAN BRAIN REGIONS COMMONLY PLAGUED BY GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii149-ii149
Author(s):  
Ayan Mandal ◽  
Rafael Romero-Garcia ◽  
Michael Hart ◽  
John Suckling
Keyword(s):  
Human Brain ◽  
Occipital Lobe ◽  
Brain Regions ◽  
Brain Dysfunction ◽  
Brain Atlas ◽  
Association Cortex ◽  
Low Grade ◽  
Expression Of Genes ◽  
Neuroimaging Data ◽  
Multiple Graph

Abstract For decades, it has been known that gliomas follow a nonrandom spatial distribution, appearing more often in some brain regions (e.g. the insula) compared to others (e.g. the occipital lobe). A better understanding of the glioma localization patterns could lend clues to the origins of these types of tumors, and consequently inform treatment targets. Following hypotheses derived from prior research into neuropsychiatric disease and cancer, gliomas may be expected to localize to brain regions characterized by functional hubness, stem-like cells, and transcription of genetic drivers of gliomagenesis. We combined neuroimaging data from 335 adult patients with high- and low-grade glioma to form a replicable tumor frequency map. Using this map, we demonstrate that glioma frequency is elevated in association cortex and correlated with multiple graph-theoretical metrics of high functional connectedness. Brain regions populated with putative cells-of-origin for glioma, neural stem cells and oligodendrocyte precursor cells, exhibited a high glioma frequency. Leveraging a human brain atlas of post-mortem gene expression, we found that gliomas were localized to brain regions enriched with expression of genes associated with chromatin organization and synaptic signaling. A set of glioma proto-oncogenes was enriched among the transcriptomic correlates of glioma distribution. Finally, a regression model incorporating connectomic, cellular, and genetic factors explained 58% of the variance in glioma frequency. These results add to previous literature reporting the vulnerability of hub regions to neurological disease, as well as provide support for cancer stem cell theories of glioma. Our findings illustrate how factors of diverse scale, from genetic to connectomic, can independently influence the anatomic localization of brain dysfunction.

scholarly journals The potential genetic network of human brain SARS-CoV-2 infection

2020 ◽  
Author(s):  
Colline Lapina ◽  
Mathieu Rodic ◽  
Denis Peschanski ◽  
Salma Mesmoudi
Keyword(s):  
Human Brain ◽  
Genetic Network ◽  
Brain Regions ◽  
Brain Atlas ◽  
Spatial Correlations ◽  
Angiotensin Converting Enzyme 2 ◽  
Over Expression ◽  
Spatially Correlated ◽  
Ace2 Gene ◽  
Mrna Expression Levels

AbstractThe literature reports several symptoms of SARS-CoV-2 in humans such as fever, cough, fatigue, pneumonia, and headache. Furthermore, patients infected with similar strains (SARS-CoV and MERS-CoV) suffered testis, liver, or thyroid damage. Angiotensin-converting enzyme 2 (ACE2) serves as an entry point into cells for some strains of coronavirus (SARS-CoV, MERS-CoV, SARS-CoV-2). Our hypothesis was that as ACE2 is essential to the SARS-CoV-2 virus invasion, then brain regions where ACE2 is the most expressed are more likely to be disturbed by the infection. Thus, the expression of other genes which are also over-expressed in those damaged areas could be affected. We used mRNA expression levels data of genes provided by the Allen Human Brain Atlas (ABA), and computed spatial correlations with the LinkRbrain platform. Genes whose co-expression is spatially correlated to that of ACE2 were then clustered into 16 groups, depending on the organ in which they are the most expressed (as described by the NCBI genes database). The list of organs where genes sharing local over-expression with the ACE2 gene are the most expressed is astonishingly similar to the organs affected by Covid-19.

scholarly journals Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas

2016 ◽  
Vol 135 (4) ◽  
pp. 425-439 ◽  
Author(s):  
Else Eising ◽  
Sjoerd M. H. Huisman ◽  
Ahmed Mahfouz ◽  
Lisanne S. Vijfhuizen ◽  
Verneri Anttila ◽  
...  
Keyword(s):  
Human Brain ◽  
Expression Analysis ◽  
Cell Types ◽  
Brain Regions ◽  
Brain Atlas ◽  
Migraine Pathophysiology

scholarly journals The Pandemic Brain: neuroinflammation in healthy, non-infected individuals during the COVID-19 pandemic

2021 ◽  
Author(s):  
Ludovica Brusaferri ◽  
Zeynab Alshelh ◽  
Daniel Martins ◽  
Minhae Kim ◽  
Akila Weerasekera ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Human Brain ◽  
Constitutive Expression ◽  
Symptom Burden ◽  
Brain Regions ◽  
Translocator Protein ◽  
Brain Atlas ◽  
Resonance Spectroscopy ◽  
Positron Emission ◽  
The Impact

The impact of COVID-19 on human health extends beyond the morbidity and death toll directly caused by the SARS-CoV-2 virus. In fact, accumulating evidence indicates a global increase in the incidence of fatigue, brain fog and depression, including among non-infected, since the pandemic onset. Motivated by previous evidence linking those symptoms to neuroimmune activation in other pathological contexts, we hypothesized that subjects examined after the enforcement of lockdown/stay-at-home measures would demonstrate increased neuroinflammation. We performed simultaneous brain Positron Emission Tomography / Magnetic Resonance Imaging in healthy volunteers either before (n=57) or after (n=15) the 2020 Massachusetts lockdown, using [11C]PBR28, a radioligand for the glial marker 18 kDa translocator protein (TSPO). First, we compared [11C]PBR28 signal across pre- and post-lockdown cohorts. Then, we evaluated the link between neuroinflammatory signals and scores on a questionnaire assessing mental and physical impacts of the pandemic. Further, we investigated multivariate associations between the spatial pattern of [11C]PBR28 post-lockdown changes and constitutive brain gene expression in post-mortem brains (Allen Human Brain Atlas). Finally, in a subset (n=13 pre-lockdown; n=11 post-lockdown), we also used magnetic resonance spectroscopy to quantify brain (thalamic) levels of myoinositol (mIns), another neuroinflammatory marker. Both [11C]PBR28 and mIns signals were overall stable pre-lockdown, but markedly elevated after lockdown, including within brain regions previously implicated in stress, depression and 'sickness behaviors'. Moreover, amongst the post-lockdown cohort, subjects endorsing higher symptom burden showed higher [11C]PBR28 PET signal compared to those reporting little/no symptoms. Finally, the post-lockdown [11C]PBR28 signal changes were spatially aligned with the constitutive expression of several genes highly expressed in glial/immune cells and/or involved in neuroimmune signaling. Our results suggest that pandemic-related stressors may have induced sterile neuroinflammation in healthy individuals that were not infected with SARS-CoV-2. This work highlights the possible impact of the COVID-19 pandemic-related lifestyle disruptions on human brain health.

scholarly journals Task-independent acute effects of delta-9-tetrahydrocannabinol on human brain function and its relationship with cannabinoid receptor gene expression: a neuroimaging meta-regression analysis

2021 ◽  
Author(s):  
Brandon Gunasekera ◽  
Cathy Davies ◽  
Grace Blest-Hopley ◽  
Mattia Veronese ◽  
Nick F Ramsey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Repeated Measures ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Brain Atlas ◽  
Angular Gyrus ◽  
Protein Distribution ◽  
Middle Temporal ◽  
Repeated Measures Design

Background: The neurobiological mechanisms underlying the effects of delta-9-tetrahydrocannabinol (THC) remain unclear. Here, we examined the spatial acute effect of THC on human on regional brain activation or blood flow (hereafter called 'activation signal') in a 'core' network of brain regions that subserve a multitude of processes. We also investigated whether the neuromodulatory effects of THC are related to the local expression of its key molecular target, cannabinoid-type-1 (CB1R) but not type-2 (CB2R) receptor. Methods: A systematic search was conducted of acute THC-challenge studies using fMRI, PET, and arterial spin labelling in accordance with established guidelines. Using pooled summary data from 372 participants, tested using a within-subject repeated measures design under experimental conditions, we investigated the effects of a single dose (6-42mg) of THC, compared to placebo, on brain signal. Findings: As predicted, THC augmented the activation signal, relative to placebo, in the anterior cingulate, superior frontal cortices, middle temporal and middle and inferior occipital gyri, striatum, amygdala, thalamus, and cerebellum crus II and attenuated it in the middle temporal gyrus (spatially distinct from the cluster with THC-induced increase in activation signal), superior temporal gyrus, angular gyrus, precuneus, cuneus, inferior parietal lobule, and the cerebellum lobule IV/V. Using post-mortem gene expression data from an independent cohort from the Allen Human Brain atlas, we found a direct relationship between the magnitude of THC-induced brain signal change, indexed using pooled effect-size estimates, and CB1R gene expression, a proxy measure of CB1R protein distribution, but not CB2R expression. A dose-response relationship was observed with THC dose in certain brain regions. Interpretation: These meta-analytic findings shed new light on the localisation of the effects of THC in the human brain, suggesting that THC has neuromodulatory effects in regions central to many cognitive tasks and processes, with greater effects in regions with higher levels of CB1R expression.

scholarly journals Alcohol use disorder causes global changes in splicing in the human brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Derek Van Booven ◽  
Mengying Li ◽  
J. Sunil Rao ◽  
Ilya O. Blokhin ◽  
R. Dayne Mayfield ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Human Brain ◽  
Alcohol Use Disorder ◽  
Brain Regions ◽  
Gene Set Enrichment Analysis ◽  
Splicing Factor ◽  
Central Nucleus ◽  
Global Changes ◽  
Aberrant Expression ◽  
Altered Expression

AbstractAlcohol use disorder (AUD) is a widespread disease leading to the deterioration of cognitive and other functions. Mechanisms by which alcohol affects the brain are not fully elucidated. Splicing constitutes a nuclear process of RNA maturation, which results in the formation of the transcriptome. We tested the hypothesis as to whether AUD impairs splicing in the superior frontal cortex (SFC), nucleus accumbens (NA), basolateral amygdala (BLA), and central nucleus of the amygdala (CNA). To evaluate splicing, bam files from STAR alignments were indexed with samtools for use by rMATS software. Computational analysis of affected pathways was performed using Gene Ontology Consortium, Gene Set Enrichment Analysis, and LncRNA Ontology databases. Surprisingly, AUD was associated with limited changes in the transcriptome: expression of 23 genes was altered in SFC, 14 in NA, 102 in BLA, and 57 in CNA. However, strikingly, mis-splicing in AUD was profound: 1421 mis-splicing events were detected in SFC, 394 in NA, 1317 in BLA, and 469 in CNA. To determine the mechanism of mis-splicing, we analyzed the elements of the spliceosome: small nuclear RNAs (snRNAs) and splicing factors. While snRNAs were not affected by alcohol, expression of splicing factor heat shock protein family A (Hsp70) member 6 (HSPA6) was drastically increased in SFC, BLA, and CNA. Also, AUD was accompanied by aberrant expression of long noncoding RNAs (lncRNAs) related to splicing. In summary, alcohol is associated with genome-wide changes in splicing in multiple human brain regions, likely due to dysregulation of splicing factor(s) and/or altered expression of splicing-related lncRNAs.

scholarly journals RNA sequencing of transcriptomes in human brain regions: protein-coding and non-coding RNAs, isoforms and alleles

BMC Genomics ◽  
2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Amy Webb ◽  
Audrey C. Papp ◽  
Amanda Curtis ◽  
Leslie C. Newman ◽  
Maciej Pietrzak ◽  
...  
Keyword(s):  
Human Brain ◽  
Rna Sequencing ◽  
Brain Regions ◽  
Protein Coding ◽  
Non Coding Rnas

scholarly journals Evolution of psychosocial burden and psychiatric symptoms in patients with psychiatric disorders during the Covid-19 pandemic

2021 ◽  
Author(s):  
Michael Belz ◽  
Philipp Hessmann ◽  
Jonathan Vogelgsang ◽  
Ulrike Schmidt ◽  
Mirjana Ruhleder ◽  
...  
Keyword(s):  
Mental Health ◽  
Mental Disorders ◽  
Psychiatric Disorders ◽  
Stress Responses ◽  
Psychiatric Symptoms ◽  
High Stress ◽  
Specific Treatment ◽  
Time Range ◽  
Long Term Effects ◽  
Psychosocial Burden

AbstractThe Covid-19 pandemic highly impacts mental health worldwide. Patients with psychiatric disorders are a vulnerable risk population for worsening of their condition and relapse of symptoms. This study investigates the pandemic-related course of psychosocial burden in patients with pre-existing mental disorders. With the newly developed Goettingen psychosocial Burden and Symptom Inventory (Goe-BSI) psychosocial burden has been traced retrospectively (1) before the pandemic (beginning of 2020), (2) at its beginning under maximum lockdown conditions (March 2020), and (3) for the current state after maximum lockdown conditions (April/May 2020). The Goe-BSI also integrates the Adjustment Disorder New Module (ADNM-20), assesses general psychiatric symptoms, and resilience. A total of 213 patients covering all major psychiatric disorders (ICD-10 F0-F9) were interviewed once in the time range from April, 24th until May 11th, 2020. Across all diagnoses patients exhibited a distinct pattern with an initial rise followed by a decline of psychosocial burden (p < 0.001, partial η2 = 0.09; Bonferroni-corrected pairwise comparisons between all three time-points: p < 0.05 to 0.001). Female gender and high ADNM-20 scores were identified as risk factors for higher levels and an unfavorable course of psychosocial burden over time. Most psychiatric symptoms remained unchanged. Trajectories of psychosocial burden vary in parallel to local lockdown restrictions and seem to reflect an adaptive stress response. For female patients with pre-existing mental disorders and patients with high-stress responses, timely and specific treatment should be scheduled. With the continuation of the pandemic, monitoring of long-term effects is of major importance, especially when long incubation times for the development of mental health issues are considered.

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