Changes In Brain Gene Expression Research Articles

Molecular plasticity to ocean warming and habitat loss in a coral reef fish.

Sea surface temperatures are rising at unprecedented rates, leading to a progressive degradation of complex habitats formed by coral reefs. In parallel, acute thermal stress can lead to physiological challenges for ectotherms that inhabit coral reefs, including fishes. Warming and habitat simplification could push marine fishes beyond their physiological limits in the near future. Specifically, questions remain on how warming and habitat structure influence the brain of marine fishes. Here we evaluated how thermal stress and habitat loss are acting independently and synergistically as stressors in a damselfish of the Western Atlantic, Abudefduf saxatilis. For this experiment, 40 individuals were exposed to different combinations of temperature (27°C or 31°C) and habitat complexity (complex vs simple) for 10 days, and changes in brain gene expression and oxidative stress of liver and muscle were evaluated. The results indicate that warming resulted in increased oxidative damage in the liver (p=0.007) and changes in gene expression of the brain including genes associated with neurotransmission, immune function, and tissue repair. Individuals from simplified habitats showed higher numbers of differentially expressed genes, and changes for genes associated with synaptic plasticity and spatial memory. In addition, a reference transcriptome of A. saxatilis is presented here for the first time, serving as a resource for future molecular studies. This project enhances our understanding of how fishes are responding to the combination of coral reef degradation and thermal stress, while elucidating the plastic mechanisms that will enable generalists to persist in a changing world.

Effects of microRNA-305 knockdown on brain gene expression associated with division of labor in honey bee colonies (Apis mellifera).

Division of labor in honey bee colonies is based on the behavioral maturation of adult workers that involves a transition from working in the hive to foraging. This behavioral maturation is associated with distinct task-related transcriptomic profiles in the brain and abdominal fat body that are related to multiple regulatory factors including juvenile hormone (JH) and queen mandibular pheromone (QMP). A prominent physiological feature associated with behavioral maturation is a loss of abdominal lipid mass as bees transition to foraging. We used transcriptomic and physiological analyses to study whether microRNAs (miRNAs) are involved in the regulation of division of labor. We first identified two miRNAs that showed patterns of expression associated with behavioral maturation, ame-miR-305-5p and ame-miR-375-3p. We then downregulated the expression of these two miRNAs with sequence-specific antagomirs. Neither ame-miR-305-5p nor ame-miR-375-3p knockdown in the abdomen affected abdominal lipid mass on their own. Similarly, knockdown of ame-miR-305-5p in combination with JH or QMP also did not affect lipid mass. By contrast, ame-miR-305-5p knockdown in the abdomen caused substantial changes in gene expression in the brain. Brain gene expression changes included genes encoding transcription factors previously implicated in behavioral maturation. The results of these functional genomic experiments extend previous correlative associations of microRNAs with honey bee division of labor and point to specific roles for ame-miR-305-5p.

Mendelian randomization analysis using GWAS and eQTL data to investigate the relationship between chronotype and neuropsychiatric disorders and their molecular basis.

Chronotype is a proxy sleep measure that has been associated with neuropsychiatric disorders. By investigating how chronotype influences risk for neuropsychiatric disorders and vice versa, we may identify modifiable risk factors for each phenotype. Here we used Mendelian randomization (MR), to explore causal effects by (1) studying the causal relationships between neuropsychiatric disorders and chronotype and (2) characterizing the genetic components of these phenotypes. Firstly, we investigated if a causal role exists between five neuropsychiatric disorders and chronotype using the largest genome-wide association studies (GWAS) available. Secondly, we integrated data from expression quantitative trait loci (eQTLs) to investigate the role of gene expression alterations on these phenotypes. Evening chronotype was causal for increased risk of schizophrenia and autism spectrum disorder and schizophrenia was causal for a tendency toward evening chronotype. We identified 12 eQTLs where gene expression changes in brain or blood were causal for one of the phenotypes, including two eQTLs for SNX19 in hippocampus and hypothalamus that were causal for schizophrenia. These findings provide important evidence for the complex, bidirectional relationship that exists between a sleep-based phenotype and neuropsychiatric disorders, and use gene expression data to identify causal roles for genes at associated loci.

The Distant Molecular Effects on the Brain by Cancer Treatment.

Cancer survivors experience cancer-related cognitive impairment (CRCI) secondary to treatment. Chemotherapy and radiation therapy independently contribute to cognitive dysfunction; however, the underlying mechanisms leading to dysfunction remain unclear. We characterized brain gene expression changes in a mouse model of CRCI to identify the mechanistic underpinnings. Eleven-to-twelve-week-old SKH1 mice were treated with doxorubicin (DOX), hindlimb radiation (RT), concurrent hindlimb radiation and doxorubicin (DOX-RT), or no treatment (control). Sixteen days following treatment, gene expression was measured from murine brains using the NanoString nCounter® glial profiling panel. Gene expression was normalized and compared between groups. No two groups shared the same expression pattern, and only Gnb1 and Srpr were upregulated in multiple treatment groups. Brains from DOX-treated mice had upregulated Atf2, Atp5b, Gnb1, Rad23b, and Srpr and downregulated Sirt5 expression compared to control brains. Brains from RT-treated mice demonstrated increased Abcg2 and Fgf2 and decreased C1qa and C1qb expression compared to control brains. Brains from DOX-RT-treated mice had upregulated Adar, E2f3, Erlec1, Gnb1, Srpr, Vim, and Pdgfra expression and downregulated Rock2 and Inpp5f expression compared to control brains. The gene expression changes demonstrated here highlight roles for neuronal transmission and oxidative stress in the pathogenesis of doxorubicin-related CRCI and inflammation in RT-related CRCI.

Long term high‐fat feeding induces cognitive impairment, alterations in microglial morphology, and spatial transcriptomic changes

AbstractBackgroundObesity and metabolic dysfunction (Metabolic Syndrome, prediabetes, and diabetes) increase the risk of later life cognitive impairment, including dementias such as Alzheimer’s Disease1‐3. One common etiology that might underly this increased risk is immune system dysregulation and inflammation4, 5. Specifically, microglial dependent mechanisms are thought to play an important role in pathology6‐8. However, the precise immune and inflammatory mechanisms promoting cognitive decline secondary to obesity and metabolic dysfunction are unclear.MethodBL6 male mice were fed 60% HFD (high fat diet) or 10% SD (standard diet) for 1 year. Body weight and glucose tolerance were assessed longitudinally. Cognition was repeatedly evaluated using Morris water maze, social recognition, and puzzle box. At study termination, mice were given either an intraperitoneal injection of lipopolysaccharide as an immune challenge or saline as a control. Activation of hippocampal microglia was assessed via immunohistochemistry (IHC) and analysis of microglial morphology. Changes in brain gene expression were measured via spatial transcriptomics using the 10X Visium platform.ResultHFD feeding caused increased weight, impaired glucose tolerance, and cognitive deficits which persisted throughout the study period. Body weight in particular was predictive of cognitive changes, especially for later time points. In response to immune challenge, hippocampal microglia in SD mice had a normal morphological response indicative of activation. However, microglia of HFD mice had no change in their morphology in response to lipopolysaccharide injection. Additionally, changes in morphology significantly correlated with cognition and indicated that a higher percentage of activated hippocampal microglia is associated with a worse cognitive phenotype. Spatial transcriptomics analysis showed changes in gene expression in multiple brain regions of HFD mice, including the hippocampus, many of which were related to neurodegenerative and inflammatory pathways.ConclusionThese data support that HFD feeding causes an early and persistent cognitive impairment, which is associated with obesity. Our data also confirm a role for microglia in HFD‐induced cognitive impairment. Indeed, microglial and transcriptomic data strongly indicate a role for inflammation and inflammatory pathways in HFD‐induced cognitive impairment.

Peripheral inflammation-induced changes in songbird brain gene expression: 3’ mRNA transcriptomic approach

Species-specific neural inflammation can be induced by profound immune signalling from periphery to brain. Recent advances in transcriptomics offer cost-effective approaches to study this regulation. In a population of captive zebra finch (Taeniopygia guttata), we compare the differential gene expression patterns in lipopolysaccharide (LPS)-triggered peripheral inflammation revealed by RNA-seq and QuantSeq. The RNA-seq approach identified more differentially expressed genes but failed to detect any inflammatory markers. In contrast, QuantSeq results identified specific expression changes in the genes regulating inflammation. Next, we adopted QuantSeq to relate peripheral and brain transcriptomes. We identified subtle changes in the brain gene expression during the peripheral inflammation (e.g. up-regulation in AVD-like and ACOD1 expression) and detected co-structure between the peripheral and brain inflammation. Our results suggest benefits of the 3′end transcriptomics for association studies between peripheral and neural inflammation in genetically heterogeneous models and identify potential targets for the future brain research in birds.

Distinct Patterns of Gene Expression Changes in the Colon and Striatum of Young Mice Overexpressing Alpha-Synuclein Support Parkinson's Disease as a Multi-System Process.

Evidence supports a role for the gut-brain axis in Parkinson's disease (PD). Mice overexpressing human wild type α- synuclein (Thy1-haSyn) exhibit slow colonic transit prior to motor deficits, mirroring prodromal constipation in PD. Identifying molecular changes in the gut could provide both biomarkers for early diagnosis and gut-targeted therapies to prevent progression. To identify early molecular changes in the gut-brain axis in Thy1-haSyn mice through gene expression profiling. Gene expression profiling was performed on gut (colon) and brain (striatal) tissue from Thy1-haSyn and wild-type (WT) mice aged 1 and 3 months using 3' RNA sequencing. Analysis included differential expression, gene set enrichment and weighted gene co-expression network analysis (WGCNA). At one month, differential expression (Thy1-haSyn vs. WT) of mitochondrial genes and pathways related to PD was discordant between gut and brain, with negative enrichment in brain (enriched in WT) but positive enrichment in gut. Linear regression of WGCNA modules showed partial independence of gut and brain gene expression changes. Thy1-haSyn-associated WGCNA modules in the gut were enriched for PD risk genes and PD-relevant pathways including inflammation, autophagy, and oxidative stress. Changes in gene expression were modest at 3 months. Overexpression of haSyn acutely disrupts gene expression in the colon. While changes in colon gene expression are highly related to known PD-relevant mechanisms, they are distinct from brain changes, and in some cases, opposite in direction. These findings are in line with the emerging view of PD as a multi-system disease.

Innate immune responses reverse HIV cognitive disease in mice: Profile by RNAseq in the brain

Antiretroviral therapy controls immunodeficiency in people with HIV but many develop mild neurocognitive disorder. Here we investigated HIV brain disease by infecting mice with the chimeric HIV, EcoHIV, and probing changes in brain gene expression during infection and reversal with polyinosinic-polycytidylic acid (poly I:C). EcoHIV-infected C57BL/6 mice were treated with poly I:C and monitored by assay of learning in radial arm water maze, RNAseq of striatum, and QPCR of virus burden and brain transcripts. Poly I:C reversed EcoHIV-associated cognitive impairment and reduced virus burden. Major pathways downregulated by infection involved neuronal function, these transcriptional changes were normalized by poly I:C treatment. Innate immune responses were the major pathways induced in EcoHIV-infected, poly I:C treated mice. Our findings provide a framework to identify brain cell genes dysregulated by HIV infection and identify a set of innate immune response genes that can block systemic infection and its associated dysfunction in the brain.

Multi-level analysis of the gut–brain axis shows autism spectrum disorder-associated molecular and microbial profiles

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut–brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD.

Tfap2b acts in GABAergic neurons to control sleep in mice

Sleep is a universal state of behavioral quiescence in both vertebrates and invertebrates that is controlled by conserved genes. We previously found that AP2 transcription factors control sleep in C. elegans, Drosophila, and mice. Heterozygous deletion of Tfap2b, one of the mammalian AP2 paralogs, reduces sleep in mice. The cell types and mechanisms through which Tfap2b controls sleep in mammals are, however, not known. In mice, Tfap2b acts during early embryonic stages. In this study, we used RNA-seq to measure the gene expression changes in brains of Tfap2b−/− embryos. Our results indicated that genes related to brain development and patterning were differentially regulated. As many sleep-promoting neurons are known to be GABAergic, we measured the expression of GAD1, GAD2 and Vgat genes in different brain areas of adult Tfap2b+/− mice using qPCR. These experiments suggested that GABAergic genes are downregulated in the cortex, brainstem and cerebellum areas, but upregulated in the striatum. To investigate whether Tfap2b controls sleep through GABAergic neurons, we specifically deleted Tfap2b in GABAergic neurons. We recorded the EEG and EMG before and after a 6-h period of sleep deprivation and extracted the time spent in NREM and in REM sleep as well as delta and theta power to assess NREM and REM sleep, respectively. During baseline conditions, Vgat-tfap2b−/− mice exhibited both shortened NREM and REM sleep time and reduced delta and theta power. Consistently, weaker delta and theta power were observed during rebound sleep in the Vgat-tfap2b−/− mice after sleep deprivation. Taken together, the results indicate that Tfap2b in GABAergic neurons is required for normal sleep.

Impact of thyroid hormone perturbations in adult mice: brain weight and blood vessel changes, gene expression variation, and neurobehavioral outcomes

Mouse models of hyper- and hypothyroidism were used to examine the effects of thyroid hormone (TH) dyshomeostasis on the aging mammalian brain. 13–14 month-old mice were treated for 4months with either levothyroxine (hyperthyroid) or a propylthiouracil and methimazole combination (PTU/Met; hypothyroid). Hyperthyroid mice performed better on Morris Water Maze than control mice, while hypothyroid mice performed worse. Brain weight was increased in thyroxine-treated, and decreased in PTU/Met-treated animals. The brain weight change was strongly correlated with circulating and tissue T4. Quantitative measurements of microvessels were compared using digital neuropathologic methods. There was an increase in microvessel area in hyperthyroid mice. Hypothyroid mice showed a trend for elevated glial fibrillary acidic protein-immunoreactive astrocytes, indicating an increase in neuroinflammation. Gene expression alterations were associated with TH perturbation and astrocyte-expressed transcripts were particularly affected. For example, expression of Gli2 and Gli3, mediators in the Sonic Hedgehog signaling pathway, were strongly impacted by both treatments. We conclude that TH perturbations produce robust neurobehavioral, pathological, and brain gene expression changes in aging mouse models.

Juvenile Exposure to BPA Alters the Estrous Cycle and Differentially Increases Anxiety-like Behavior and Brain Gene Expression in Adult Male and Female Rats

Perinatal exposure to bisphenol A (BPA) in murine models has been reported to affect social behavior and increase anxiety. However, there is little information about the effects of BPA exposure during puberty, a period in which sex hormones influence the maturation and differentiation of the brain. In this work, we evaluated the effect of BPA administration during the juvenile stage (PND 21–50) on anxiety in male and female rats. Newly weaned Wistar rats were treated with BPA (0, 50, or 500 µg/kg/day) for 30 days. To compare the intra- and inter-sex behavioral profiles, rats were evaluated using four different anxiety models: the Open field test (OFT), the Elevated plus maze (EPM), the Light-dark box test (LDBT), and the Defensive burying test (DBT). Males exhibited a clear-cut anxious profile at both doses in all four tests, while no clear behavioral effect of BPA exposure was observed in female rats. The latter showed an altered estrous cycle that initiated earlier in life and had a shorter duration, with the estrous phase predominating. Moreover, the expression of ESR1, ESR2, GABRA1, GRIN1, GR, MR, and AR genes increased in the hippocampus and hypothalamus of male rats treated with 50 µg/kg, but not in females. Our results indicate that BPA consistently induces a higher anxiety profile in male than in female rats, as evidenced predominantly by an increase in passive-coping behaviors and changes in brain gene expression, highlighting the importance of sex in peripubertal behavioral toxicology studies.

Gene expression and chromatin conformation differs between worker bees performing different tasks

BackgroundRevealing the effect of transcriptomic regulation on behavioral differences is a fundamental goal in biology, but the relationship between gene regulatory networks and individual behavior differences remains largely unknown. Honey bees are considered as good models for studying the mechanisms underlying gene expression changes and behavioral differences since they exhibit strong and obvious differences in tasks between individuals. The cis-regulatory regions usually contain the binding sites of diverse transcription factor (TFs) influencing bee behavior. Thus, the identification of cis-regulatory elements in the brains across different behavioral states is important for understanding how genomic and transcriptomic variations affect different tasks in honeybees. MethodsIn this study, we employed transcriptome and genome-wide chromatin accessibility assays to analyze brain tissues of honey bees in different behavioral states for examining the relationship between individual behavior differences and brain gene expression changes. We also used the obtained open chromatin regions to identify cis-motifs associating differentially expressed TFs and genes in order to reveal the transcriptional regulatory mechanism related to the different tasks. ResultsWe identified genetic regulatory modules regulating different tasks that contained key TFs (CTCF, Trl and schlank) associated with open chromatin regions enriched for DNA sequence motifs belonging to the family of the corresponding TFs. The most prominent transcriptomic changes, which correlated with chromatin accessibility modifications within their proximal promoter regions, occurred in nervous system development, and were associated with behavior switch. ConclusionsOur results revealed the regulatory landscape among three behavioral stages in honeybees and identified interactive molecular networks regulating different tasks. These results provide a comprehensive insight into behavioral differences of honeybees, which offers reference for future study.

Conservation of mechanisms regulating emotional-like responses on spontaneous nicotine withdrawal in zebrafish and mammals

BackgroundNicotine withdrawal syndrome is a major clinical problem. Animal models with sufficient predictive validity to support translation of pre-clinical findings to clinical research are lacking. AimsWe evaluated the behavioural and neurochemical alterations in zebrafish induced by short- and long-term nicotine withdrawal. MethodsZebrafish were exposed to 1 mg/L nicotine for 2 weeks. Dependence was determined using behavioural analysis following mecamylamine-induced withdrawal, and brain nicotinic receptor binding studies. Separate groups of nicotine-exposed and control fish were assessed for anxiety-like behaviours, anhedonia and memory deficits following 2–60 days spontaneous withdrawal. Gene expression analysis using whole brain samples from nicotine-treated and control fish was performed at 7 and 60 days after the last drug exposure. Tyrosine hydroxylase (TH) immunoreactivity in pretectum was also analysed. ResultsMecamylamine-precipitated withdrawal nicotine-exposed fish showed increased anxiety-like behaviour as evidenced by increased freezing and decreased exploration. 3H-Epibatidine labeled heteromeric nicotinic acethylcholine receptors (nAChR) significantly increased after 2 weeks of nicotine exposure while 125I-αBungarotoxin labeled homomeric nAChR remained unchanged. Spontaneous nicotine withdrawal elicited anxiety-like behaviour (increased bottom dwelling), reduced motivation in terms of no preference for the enriched side in a place preference test starting from Day 7 after withdrawal and a progressive decrease of memory attention (lowering discrimination index). Behavioural differences were associated with brain gene expression changes: nicotine withdrawn animals showed decreased expression of chrna 4 and chrna7 after 60 days, and of htr2a from 7 to 60 days.The expression of c-Fos was significantly increased at 7 days. Finally, Tyrosine hydroxylase (TH) immunoreactivity increased in dorsal parvocellular pretectal nucleus, but not in periventricular nucleus of posterior tuberculum nor in optic tectum, at 60 days after withdrawal. ConclusionsOur findings show that nicotine withdrawal induced anxiety-like behaviour, cognitive alterations, gene expression changes and increase in pretectal TH expression, similar to those observed in humans and rodent models.

Agonal Factors Distort Gene-Expression Patterns in Human Postmortem Brains.

Agonal factors, the conditions that occur just prior to death, can impact the molecular quality of postmortem brains, influencing gene expression results. Our study used gene expression data of 262 samples from ROSMAP with the detailed terminal state recorded for each donor, such as fever, infection, and unconsciousness. Fever and infection were the primary contributors to brain gene expression changes, brain cell-type-specific gene expression, and cell proportion changes. Furthermore, we also found that previous studies of gene expression in postmortem brains were confounded by agonal factors. Therefore, correction for agonal factors is important in the step of data preprocessing. Our analyses revealed fever and infection contributing to gene expression changes in postmortem brains and emphasized the necessity of study designs that document and account for agonal factors.

A unique neurogenomic state emerges after aggressive confrontations in males of the fish Betta splendens.

Territorial defense involves frequent aggressive confrontations with competitors, but little is known about how brain-transcriptomic profiles change between individuals competing for territory establishment. Our previous study elucidated that when two fish Betta splendens males interact, transcriptomes across their brains synchronize in a way that reflects a mutual assessment process between them at the gene expression level. Here we aim to evaluate how the brain-transcriptomic profiles of opponents change immediately after shifting their social status (i.e., the winner/loser has emerged) and 30min after this shift. We showed that changes in the expression of certain genes are unique to different fighting stages and the expression patterns of certain genes are transiently or persistently changed across all fighting stages. These brain transcriptomic responses are in accordance with behavioral changes across the fight. Strikingly, the specificity of the brain-transcriptomic synchronization of a pair during fighting was gradually lost after fighting ceased, leading to the emergence of a basal neurogenomic state in which the changes in gene expression were reduced to minimum and consistent across all individuals. This state shares common characteristics with the hibernation state that animals adopt to minimize their metabolic rates to save energy. Interestingly, expression changes for genes related to metabolism, autism spectrum disorder, and long-term memory still differentiated losers from winners. Together, the fighting system using male B. splendens provides a promising platform for investigating neurogenomic states of aggression in vertebrates.

Fetal Bisphenol-A Induced Changes in Murine Behavior and Brain Gene Expression Persisted in Adult-aged Offspring.

In utero Bisphenol A (BPA) exposure has been linked to many deficits during brain development, including sexual differentiation, behavior, and motor coordination. Yet, how BPA induces these disorders and whether its effects are long lasting are largely unknown. In this study, using a mouse model, we demonstrated that in utero exposure to an environmentally relevant dose of BPA induced locomotor deficits, anxiety-like behavior, and declarative memory impairments that persisted into old age (18 months). Compared to the control animals, the BPA-exposed mice had a significant decrease in locomotor activity, exploratory tendencies, and long-term memory, and an increase in anxiety. The global brain gene expression profile was altered permanently by BPA treatment and showed regional and sexual differences. The BPA-treated male mice had more changes in the hippocampus, while female mice experienced more changes in the cortex. Overall, we demonstrate that in utero exposure to BPA induces permanent changes in brain gene expression in a region-specific and sex-specific manner, including a significant decrease in locomotor activity, learning ability, long-term memory, and an increase in anxiety. Fetal/early life exposures permanently affect neurobehavioral functions that deteriorate with age; BPA exposure may compound the effects of aging.

Brain regional gene expression network analysis identifies unique interactions between chronic ethanol exposure and consumption.

Progressive increases in ethanol consumption is a hallmark of alcohol use disorder (AUD). Persistent changes in brain gene expression are hypothesized to underlie the altered neural signaling producing abusive consumption in AUD. To identify brain regional gene expression networks contributing to progressive ethanol consumption, we performed microarray and scale-free network analysis of expression responses in a C57BL/6J mouse model utilizing chronic intermittent ethanol by vapor chamber (CIE) in combination with limited access oral ethanol consumption. This model has previously been shown to produce long-lasting increased ethanol consumption, particularly when combining oral ethanol access with repeated cycles of intermittent vapor exposure. The interaction of CIE and oral consumption was studied by expression profiling and network analysis in medial prefrontal cortex, nucleus accumbens, hippocampus, bed nucleus of the stria terminalis, and central nucleus of the amygdala. Brain region expression networks were analyzed for ethanol-responsive gene expression, correlation with ethanol consumption and functional content using extensive bioinformatics studies. In all brain-regions studied the largest number of changes in gene expression were seen when comparing ethanol naïve mice to those exposed to CIE and drinking. In the prefrontal cortex, however, unique patterns of gene expression were seen compared to other brain-regions. Network analysis identified modules of co-expressed genes in all brain regions. The prefrontal cortex and nucleus accumbens showed the greatest number of modules with significant correlation to drinking behavior. Across brain-regions, however, many modules with strong correlations to drinking, both baseline intake and amount consumed after CIE, showed functional enrichment for synaptic transmission and synaptic plasticity.

Meta-analysis of honey bee neurogenomic response links Deformed wing virus type A to precocious behavioral maturation

Crop pollination by the western honey bee Apis mellifera is vital to agriculture but threatened by alarmingly high levels of colony mortality, especially in Europe and North America. Colony loss is due, in part, to the high viral loads of Deformed wing virus (DWV), transmitted by the ectoparasitic mite Varroa destructor, especially throughout the overwintering period of a honey bee colony. Covert DWV infection is commonplace and has been causally linked to precocious foraging, which itself has been linked to colony loss. Taking advantage of four brain transcriptome studies that unexpectedly revealed evidence of covert DWV-A infection, we set out to explore whether this effect is due to DWV-A mimicking naturally occurring changes in brain gene expression that are associated with behavioral maturation. Consistent with this hypothesis, we found that brain gene expression profiles of DWV-A infected bees resembled those of foragers, even in individuals that were much younger than typical foragers. In addition, brain transcriptional regulatory network analysis revealed a positive association between DWV-A infection and transcription factors previously associated with honey bee foraging behavior. Surprisingly, single-cell RNA-Sequencing implicated glia, not neurons, in this effect; there are relatively few glial cells in the insect brain and they are rarely associated with behavioral plasticity. Covert DWV-A infection also has been linked to impaired learning, which together with precocious foraging can lead to increased occurrence of infected bees from one colony mistakenly entering another colony, especially under crowded modern apiary conditions. These findings provide new insights into the mechanisms by which DWV-A affects honey bee health and colony survival.

A Portal to Visualize Transcriptome Profiles in Mouse Models of Neurological Disorders

Target nomination for drug development has been a major challenge in the path to finding a cure for several neurological disorders. Comprehensive transcriptome profiles have revealed brain gene expression changes associated with many neurological disorders, and the functional validation of these changes is a critical next step. Model organisms are a proven approach for the elucidation of disease mechanisms, including screening of gene candidates as therapeutic targets. Frequently, multiple models exist for a given disease, creating a challenge to select the optimal model for validation and functional follow-up. To help in nominating the best mouse models for studying neurological diseases, we developed a web portal to visualize mouse transcriptomic data related to neurological disorders. Users can examine gene expression changes across mouse model studies to help select the optimal mouse model for further investigation. The portal provides access to mouse studies related to Alzheimer’s diseases (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic Lateral Sclerosis (ALS), Spinocerebellar ataxia (SCA), and models related to aging.