Gene Expression In Brain Research Articles

Ketogenic Diet Reduces Age-Induced Chronic Neuroinflammation in Mice.

The ketone body beta-hydroxybutyrate (BHB) is an acidic energy metabolite that is synthesized during periods of fasting or exercise. Our previous study demonstrated that an every other week cyclic ketogenic diet (Cyclic KD), which induces blood BHB levels similar to those observed during fasting, reduces midlife mortality and improves memory in aging mice. In addition to its canonical role as an energy metabolite, BHB regulates gene expression and inflammatory activation through non-energetic signaling pathways. The precise mechanisms by which BHB or KD affects brain function during aging remain incompletely understood. Using bulk RNA-sequencing (RNA-Seq), we examined whole brain gene expression of 12-month-old C57BL/6JN male mice fed KD for either one week or 14 months. While one-week KD increases some inflammatory gene expression, the 14-month Cyclic KD largely reduces age-induced neuroinflammatory gene expression. Next, a gene expression analysis of human primary brain cells (microglia, astrocytes, and neurons) using RNA-Seq revealed that BHB alone induces a mild level of inflammation in all three cell types. However, BHB inhibits the more pronounced inflammatory gene expression induced by lipopolysaccharide (LPS) in microglia. BHB exhibits a comparable inhibitory effect on LPS-induced inflammation in mouse primary microglia, which we used as an in vitro model to test and exclude known mechanisms by which BHB regulates inflammation and gene expression as responsible for this modulation of LPS-induced inflammatory gene expression. An acidic milieu resulting from BHB may be required for or contribute to the effect. Overall, we observe that BHB has the potential to attenuate the microglial response to inflammatory stimuli, such as LPS. This may contribute to an observed reduction in chronic inflammation in the brain following long-term Cyclic KD treatment in aging mice.

Managing the tradeoff between reproduction and survival requires flexibility in behaviour and gene regulation in three-spined stickleback.

Predators exert a powerful selective force, however, predator avoidance can conflict with other important activities such as attracting mates. Decisions over whether to court mates versus avoiding predators are vital to fitness, yet the mechanistic underpinnings of how animals manage such tradeoffs are poorly understood. Here, we investigate the flexibility of behaviour and gene regulation in response to a tradeoff between avoiding predators (survival) and courting potential mates (reproduction) in three-spined stickleback (Gasterosteus aculeatus). We compared behavioural and transcriptomic responses of male sticklebacks faced with a courtship opportunity and cues of a predator simultaneously with the responses of males faced with a courtship opportunity or cues of a predator alone, and found that males behaviourally compromised courtship in favour of predator avoidance when faced with a tradeoff between them. The need to manage this tradeoff elicited dynamic changes in brain gene expression, and sets of functionally connected genes were organized into discrete modules based on co-expression. Additionally, we found that behavioural flexibility in response to tradeoffs corresponded to flexibility in gene regulatory network structure. Combined, these results uncover the coordinated response by the brain to a fundamental ecological tradeoff, providing insight into the structure and function of genetic networks underpinning how animals make fitness-influencing decisions.

Differences in cerebral spontaneous neural activity correlate with gene-specific transcriptional signatures in primary angle-closure glaucoma.

This study was aimed to investigate frequency-specific LFO changes and their correlation with gene pathways in PACG using transcriptome-neuroimaging analysis. Resting-state fMRI (Rs-fMRI) data were acquired from individuals with PACG and healthy controls for evaluating the amplitude of low-frequency oscillations (ALFF) across different frequency bands such as the full band, slow-4 band, and slow-5 band. Transcriptome analysis integrated information from the Allen Human Brain Atlas (AHBA) through gene set enrichment analysis, protein-protein interaction network construction, and specific expression analysis, aiming to clarify the link between ALFF patterns and gene expression profiles in PACG. Statistical analyses, including one-sample t-tests and two-sample t-tests, were used to assess ALFF differences between groups, while partial least squares (PLS) regression was applied to explore the associations between ALFF and transcriptome data. This study identifies significant variations in ALFF values in PACG patients, observed consistently across multiple frequency bands, including slow-4 and slow-5. Enrichment analysis indicates that these genes are primarily involved in cellular components such as the cytosol and cytoplasm, molecular functions like protein binding, and key pathways, including metabolic and circadian rhythms, epithelial signaling in Helicobacter pylori infection, and glutathione metabolism. Protein-protein interaction (PPI) analysis further underscores the role of PACG-related genes in forming a functional network, highlighting hub genes critical for various biological processes. This study establishes a connection between the molecular mechanisms of PACG and alterations in brain function and gene expression, providing valuable perspectives on the fundamental processes impacting low-frequency oscillations in PACG.

Gene expression is associated with brain function of insomnia disorder, rather than brain structure

Previous research has found brain structural and functional abnormalities in patients with insomnia disorder (ID). However, the relationship between brain abnormalities in ID and brain gene expression is unclear. This study explored the relationship between gene expression and brain structural or functional abnormalities in ID, and we validated the reliability of the results with two independent datasets (discover dataset: healthy control (HC) = 129, ID = 264; validation dataset: HC = 160, ID = 115). Brain imaging results show that ID has abnormal resting-state spontaneous activity, regional homogeneity, and widespread gray matter volume reduction compared to HC. The association analysis results with gene expression further revealed that brain function abnormalities in ID were significantly associated with gene expression, but structural abnormalities were not. This study establishes a link between transcriptional changes and brain functional abnormalities in ID, revealing a genetic basis that may involve several biological pathways. Specifically, these pathways include hormonal regulation of the hypothalamic-pituitary-adrenal (HPA) axis, which plays a crucial role in stress response and sleep regulation; ion transport across membranes, vital for neuronal communication; and inhibitory neuronal regulation, essential for maintaining normal brain function. Furthermore, the ID-related genes are enriched for brain tissue and cortical cells, emphasizing their relevance in understanding the biological underpinnings of ID.

From Nutritional Patterns to Behavior: High-Fat Diet Influences on Inhibitory Control, Brain Gene Expression, and Metabolomics in Rats.

Impulsive and compulsive behaviors are associated with inhibitory control deficits. Diet plays a pivotal role in normal development, impacting both physiology and behavior. However, the specific effects of a high-fat diet (HFD) on inhibitory control have not received adequate attention. This study aimed to explore how exposure to a HFD from postnatal day (PND) 33 to PND77 affects impulsive and compulsive behaviors. The experiment involved 40 Wistar rats subjected to HFD or chow diets. Several tasks were employed to assess behavior, including variable delay to signal (VDS), five choice serial reaction time task (5-CSRTT), delay discounting task (DDT), and rodent gambling task (rGT). Genetic analyses were performed on the frontal cortex, and metabolomics and fatty acid profiles were examined by using stool samples collected on PND298. Our results showed that the HFD group exhibited increased motor impulsive behaviors while not affecting cognitive impulsivity. Surprisingly, reduced impulsive decision-making was shown in the HFD group. Furthermore, abnormal brain plasticity and dopamine gene regulation were shown in the frontal cortex, while metabolomics revealed abnormal fatty acid levels.

Differential effects of prenatal alcohol exposure on brain growth reveals early upregulation of cell cycle and apoptosis and delayed downregulation of metabolism in affected offspring.

Fetal Alcohol Spectrum Disorder (FASD) encompasses the deleterious consequences of Prenatal Alcohol Exposure (PAE), including developmental delay, microcephaly, dysmorphologies, and cognitive and behavioral issues. The dose and timing of alcohol exposure, maternal and environmental factors, and genetics all impact FASD outcomes, but differential susceptibility and resiliency to PAE remains poorly understood. In this study, we examined the differential effects of PAE during early mouse development on brain growth and gene expression. Brains were weighed and collected either 24 hours or five days after treatment. We then performed transcriptomics to determine whether offspring differentially affected by PAE, by brain weight, also differ in gene expression, despite having the same genetic background, alcohol exposure, and maternal factors. We found within litter variation in brain weights after PAE, and classified offspring as having normal, middle, and low-weight brains relative to saline-treated controls. The normal-weight brains showed no significant differences in gene expression, suggesting these offspring were both phenotypically and transcriptionally unaffected by PAE. While both middle- and low-weight brains showed changes in gene expression, the middle-weight brains showed the most robust transcriptome differences. Twenty-four hours after PAE, we saw an upregulation of cell cycle and apoptosis in affected offspring, whereas at roughly a week later, we saw a downregulation of metabolic processes. Overall, these findings highlight variability in response to PAE and demonstrate the molecular processes involved in offspring phenotypically affected by alcohol.

Threshold of defensive response in Apis mellifera (honey bees) and subsequent brain gene expression in reaction to noxious stimuli

Threshold of defensive response in <i>Apis mellifera</i> (honey bees) and subsequent brain gene expression in reaction to noxious stimuli

Sex differences of negative emotions in adults and infants along the prefrontal-amygdaloid brain pathway

The neural basis of sex-related differences in processing negative emotions remains poorly understood. The amygdala-related fiber pathways serve as the neuroanatomical foundation for emotion processing. However, the precise sex-related variations within these pathways remain largely elusive. Using diffusion magnetic resonance imaging data from 418 healthy individuals, we identified sex differences in white-matter microstructures of the striato-amygdaloid-prefrontal tracts, particularly the amygdala (Amy)-medial prefrontal cortex (mPFC) pathway. These differences were associated with various neurobiological factors, including pain-related negative emotions, pain sensitivity, neurotransmitter receptors, and gene expressions in the human brain. Our findings suggested that the Amy-mPFC pathway may serve as a neuroanatomical foundation for sex-specific negative emotion processing, driven by specific genetic and neurotransmitter profiles. Notably, we also found similar sex differences in this pathway in an infant imaging dataset, hinting at its developmental significance as a precursor to sex differences in adulthood. These findings underscore the importance of the striato-amygdaloid-prefrontal tracts in sex-related differences in processing negative emotions. This may enhance our understanding of sex-specific emotion regulation and potentially inform future research on strategies for preventing and diagnosing emotional regulation disorders across sexes.

Effects of chronodisruption and alcohol consumption on gene expression in reward-related brain areas in female rats.

Circadian dysfunction caused by exposure to aberrant light-dark conditions is associated with abnormal alcohol consumption in humans and animal models. Changes in drinking behavior have been linked to alterations in clock gene expression in reward-related brain areas, which could be attributed to either the effect of chronodisruption or alcohol. To date, however, the combinatory effect of circadian disruption and alcohol on brain functions is less understood. Moreover, despite known sex differences in alcohol drinking behavior, most research has been carried out on male subjects only, and therefore implications for females remain unclear. To address this gap, adult female rats housed under an 11 h/11 h light-dark cycle (LD22) or standard light conditions (LD24, 12 h/12 h light-dark) were given access to an intermittent alcohol drinking protocol (IA20%) to assess the impact on gene expression in brain areas implicated in alcohol consumption and reward: the prefrontal cortex (PFC), nucleus accumbens (NAc), and dorsal striatum (DS). mRNA expression of core clock genes (Bmal1, Clock, Per2), sex hormone receptors (ERβ, PR), glutamate receptors (mGluR5, GluN2B), a calcium-activated channel (Kcnn2), and an inflammatory cytokine (TNF-α) were measured at two-time points relative to the locomotor activity cycle. Housing under LD22 did not affect alcohol intake but significantly disrupted circadian activity rhythms and reduced locomotion. Significant changes in the expression of Bmal1, ERβ, and TNF-α were primarily related to the aberrant light conditions, whereas changes in Per2 and PR expression were associated with the effect of alcohol. Collectively, these results indicate that disruption of circadian rhythms and/or intermittent alcohol exposure have distinct effects on gene expression in the female brain, which may have implications for the regulation of alcohol drinking, addiction, and, ultimately, brain health.

Reported race-associated differences in control and schizophrenia post-mortem brain transcriptomes implicate stress-related and neuroimmune pathways.

The molecular mechanisms underlying racial disparities in schizophrenia (SCZ) illness courses and outcomes are poorly understood. While these differences are thought to arise partly through stressful social gradients, little is known about how these differences are reflected in the brain, nor how they might underlie disparate psychiatric outcomes. To better understand the neuro-molecular correlates of social gradients, SCZ, and their overlap, we analyzed post-mortem dorsolateral prefrontal cortex (DLPFC) RNAseq data from two racially diverse cohorts in the CommonMind Consortium (235 reported Black and 546 White, 322 SCZ cases and 459 controls) using differential expression and gene set variation analyses. We observed differences in brain gene expression that were consistent across cohorts and reported race. A combined mega-analysis identified 1,514 genes with differential expression (DE) between reported race groups after accounting for diagnosis and other covariates. Functional enrichment analyses identified upregulation of genes involved in stress and immune response, highlighting the potential role of environmental differences between reported race groups. In a race-by-diagnosis interaction analysis, no individual genes passed statistical significance. However, 109 gene sets showed statistically significant differences, implicating metabolic and immune pathways. Our results suggest molecular mechanisms uniquely perturbed across reported race groups and identify several candidate pathways associated with SCZ in a reported race-dependent manner. Our results underscore the importance of diverse cohort ascertainment to better capture population-level differences in SCZ pathogenesis.

Ketogenic diet and its treatment for brain and other nervous system cancers

Abstract. A growing body of empirical evidence indicates the paramount importance of nutrition in cancer treatment, especially glioma. Among the various strategies proposed to enhance traditional anticancer therapy, ketogenic diets (KD) have emerged as a noteworthy approach. In this review, seven papers highly relevant to the effects of ketogenic diet on glioma are selected and the factors involved are summarized. A Google Scholar search with the subject terms ketogenic diet and brain cancer or ketone bodies and glioma results in the selection of seven papers highly relevant to the topic. Animals injected with tumor cells or patients diagnosed with glioma, which had received a ketogenic diet for at least ten days, are included in the analysis. The metabolism-related measurements are also taken. The seven papers show that the ketogenic diet can lower glucose levels, increase -OHB levels, and reduce tumor size or weight. Additionally, it can also impact brain tumor vascularity and gene expression and potentially influence survival time, making it a promising approach for managing brain cancer in humans. In conclusion, there is evidence showing that the Ketogenic diet has the potential to treat brain cancer. Due to the duration and sample volume of the previous studies, future research still needs to continue.

Genetic Influence of the Brain on Muscle Structure: A Mendelian Randomization Study of Sarcopenia.

The association between brain and sarcopenia has not been clarified. We aim to investigate the causal association between brain structure, function, gene expression and sarcopenia-related traits. All participants were Europeans. GWAS data of Brain Imaging Data Structure (BIDs) was from the UK Biobank. Gene expression in 13 brain regions was acquired from the GTEx Consortium. The sarcopenia-related traits, including appendicular lean mass (ALM), whole body lean mass (WBLM), grip strength and sarcopenia diagnosed by the European Working Group on Sarcopenia in Older People (EWGSOP) or Foundation for the National Institutes of Health (FNIH), were from the IEU website. The inverse variance weighted (IVW), MR Egger, weighted median, weighted mode and Wald ratio methods were used for a two-sample Mendelian randomization (MR) analysis between brain structures and sarcopenia-related traits. The summary-data-based MR (SMR) was used to investigate brain genes causally influencing sarcopenia. We calculated the F-value, odds ratio with 95% CI and p-value. For the sensitivity analysis, the heterogeneity I2 statistic, Cochrane's Q test, Egger's intercept test, MR-PRESSO and the leave-one-out sensitivity test were used. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction (PPI), transcription factor interaction prediction and miRNA interaction prediction analysis were used to reveal potential signalling pathways and mechanisms. We included 3144 imaging phenotypes from 8428 participants in BIDs data. One hundred forty-one BIDs were identified to causally influence ALM, 160 BIDs showed significant causal effect on the WBLM, and 86 BIDs showed significant causal effect on grip strength. There were 48 or 32 BIDs causally associated with sarcopenia diagnosed by the EWGSOP or FNIH criteria respectively. After FDR correction, there were 35 BIDs showing causal effect on the ALM, 28 BIDs showing causal effect on the WBLM and 7 BIDs showing causal effect on grip strength (p < 0.05). Twelve to forty-eight genes in different brain regions showed causal effect on all the five sarcopenia-related traits. MMP24-AS1, HLA-DRB6, HLA-DQA2, DDX42, BAG6, NUSAP1, LINC00940, NME1-NME2 and AS3MT in the amygdala region showed detrimental effect on all the five sarcopenia-related traits, whereas HLA-DRB1, HLA-DQB1-AS1 and C6ORF3 showed protective effect (p < 0.05). The gene enrichment analysis indicated these screened genes was mainly enriched in immune-related signalling. We discovered the causal effect of BIDs and brain gene expression on sarcopenia. The positive genes were mainly enriched in immune-related signalling, suggesting an immune-based cross-organ regulation mechanism of brain-muscle axis.

Spatial Transcriptomics and Single-Nucleus Multi-Omics Analysis Revealing the Impact of High Maternal Folic Acid Supplementation on Offspring Brain Development.

Background: Folate, an essential vitamin B9, is crucial for diverse biological processes, including neurogenesis. Folic acid (FA) supplementation during pregnancy is a standard practice for preventing neural tube defects (NTDs). However, concerns are growing over the potential risks of excessive maternal FA intake. Objectives/Methods: Here, we employed a mouse model and spatial transcriptomic and single-nucleus multi-omics approaches to investigate the impact of high maternal FA supplementation during the periconceptional period on offspring brain development. Results: Maternal high FA supplementation affected gene pathways linked to neurogenesis and neuronal axon myelination across multiple brain regions, as well as gene expression alterations related to learning and memory in thalamic and ventricular regions. Single-nucleus multi-omics analysis revealed that maturing excitatory neurons in the dentate gyrus (DG) are particularly vulnerable to high maternal FA intake, leading to aberrant gene expressions and chromatin accessibility in pathways governing ribosomal biogenesis critical for synaptic formation. Conclusions: Our findings provide new insights into specific brain regions, cell types, gene expressions and pathways that can be affected by maternal high FA supplementation.

Identification of Risk Genes for Attention-Deficit/Hyperactivity Disorder During Early Human Brain Development

ObjectiveAttention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder with high heritability. Demontis et al. (2023) identified 27 genome-wide significant loci for ADHD through genome-wide association studies (GWASs), but the identification of risk genes that confer susceptibility to ADHD has remained largely unexplored. MethodAs ADHD is a neurodevelopmental disorder, we integrated human brain prenatal gene and transcript expression weight data (n=120) and ADHD GWAS summary statistics (n=225,534; 38,691 cases and 186,843 controls) to perform a transcriptome-wide association study (TWAS) by FUSION (an analytic suite). ResultsOur analysis identified 10 genes, including LSM6, HYAL3, METTL15, RPS26, LRRC37A15P, RP11-142I20.1, ABCB9, AP006621.5, AC000068.5, and PDXDC1, that are significantly associated with ADHD, along with 8 transcripts of 7 genes. We also conducted TWAS analysis using CommonMind Consortium (CMC) adult brain gene and splicing expression weights (n=452), which highlighted several risk genes that showed associations with ADHD in both prenatal and postnatal stages, such as LSM6 and HYAL3. ConclusionOverall, our TWAS of ADHD, by integrating human prenatal brain transcriptome and ADHD GWAS results, uncovered the cis-effects of gene/transcript regulation that are predicted to be associated with ADHD. By combining colocalization and FOCUS fine-mapping analysis, we further unraveled potential causal candidate risk genes. The risk genes/transcripts we identified in this study can serve as a valuable resource for further investigation of the disease mechanisms underlying ADHD.

Chronic exposure to low concentration of diflubenzuron and pyriproxyfen induces brain oxidative stress and inflammation and alters locomotion in zebrafish (Danio rerio)

Diflubenzuron (DFB1) and pyriproxyfen (PPF) are pesticides widely used in agriculture and urban environments to control insect actions. The aim of this study was to evaluate the effects of chronic 30-day exposure to DFB (0.025 and 0.125 mg/L) and PPF (0.379 and 0.758 mg/L) on the behavior of juvenile zebrafish (Danio rerio). Fish were exposed to insecticides from early stage (4 h post fertilization) to 30 days post fertilization (dpf). At 45 dpf, fish were evaluated in the novel tank test, social behavior test, and mirror aggressive test. Brain gene expression related to oxidative stress and inflammation was also evaluated. DFB reduced locomotor parameters in the novel tank and aggression tests, while it induced to hyperactivity in the social behavior test. PPF reduced anxiety-like behavior, measured by the time spent in risky areas of the novel tank, and reduced aggression against the mirror image. There was a significant reduction in mRNA levels of the nfe2l2 gene (∼0.54 fold downregulated) and increase in levels of cat (PPF ∼1.8 fold change), gsr (PPF ∼1.5 fold change), gpx1a (PPF ∼1.6 and DFB 1.1 fold change), tnf-α (PPF 1.9 and DFB 2.2 fold change), and il-6 (PPF ∼1.2 and DFB 2.3 fold change). These endpoints are indicative of the threatening effects of insecticides to aquatic organisms and the need for alternative methods to control pests by using less harmful and safer substances for animal and human well-being, as well as for the environment.

MK-801-exposure induces increased translation efficiency and mRNA hyperacetylation of Grin2a in the mouse prefrontal cortex

ABSTRACT Acute exposure to MK-801, the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, induces schizophrenia-like behavioural changes in juvenile male mice. However, the effects of acute MK-801 exposure on brain gene expression at the translation level remain unclear. Here, we conducted ribosome profiling analysis on the prefrontal cortex (PFC) of acute MK-801-exposed juvenile male mice. We found 357 differentially translated genes, with the N 4-acetylcytidine (ac4C) consensus motif enriched in the transcripts with increased translation efficiency. Acetylated RNA immunoprecipitation sequencing revealed 148 differentially acetylated peaks, of which 121 were hyperacetylated, and 27 were hypoacetylated. Genes harbouring these peaks were enriched in pathways related to axon guidance, Hedgehog signalling pathway, neuron differentiation, and memory. Grin2a encodes an NMDA receptor subunit NMDAR2A, and its human orthologue is a strong susceptibility gene for schizophrenia. Grin2a mRNA was hyperacetylated and exhibited significantly increased translation efficiency. NMDAR2A protein level was increased in MK-801-exposed PFC. Pretreatment of Remodelin, an inhibitor of N-acetyltransferase 10, returned the NMDAR2A protein levels to normal and partially reversed schizophrenia-like behaviours of MK-801-exposed mice, shedding light on the possible role of mRNA acetylation in the aetiology of schizophrenia.

Lactic acid bacteria supplementation: A bioprotective approach to mitigating cadmium-induced toxicity and modulating gene expression in murine models

This study aimed to assess the effects of different strains of lactic acid bacteria, namely LeviLactobacillus brevis (AC10), Lacticaseibacillus rhamnosus (AC11), and Pediococcus acidilactici (AC15), on mice exposed to cadmium-induced oxidative stress. The study assessed weight gain, liver enzymes, antioxidant enzymes, immunoglobulin factors, lipid peroxidation, and gene expression in liver and brain of mice. The findings revealed that the AC10 and AC11 strains had a higher ability to absorb Cd as compared to AC15. The in vivo analysis demonstrated that the dietary dual supplementation of AC10 and AC11 resulted in significant (p < 0.05) improvements, including increased body weight and food intake, reduced cadmium tissue deposition, decreased lipid peroxidation, enhanced cellular antioxidant redox potential, suppressed inflammation genes in the liver and brain tissues, and improved morpho-characteristics of the jejunum in mice challenged by cadmium-induced toxicity. The multiple mechanisms of action, including heavy metal sequestration, antioxidant enhancement, and maintenance of intestinal integrity, highlight the potential of these probiotics’ intervention as a viable approach to counteract the deleterious effects of cadmium exposure.

Brain gene expression reveals pathways underlying nocturnal migratory restlessness

Migration is one of the most extreme and energy demanding life history strategies to have evolved in the animal kingdom. In birds, champions of long-distance migrations, the seasonal emergence of the migratory phenotype is characterised by rapid physiological and metabolic remodelling, including substantial accumulation of fat stores and increases in nocturnality. The molecular underpinnings and brain adaptations to seasonal migrations remain poorly understood. Here, we exposed Common quails (Coturnix coturnix) to controlled changes in day length to simulate southward autumn migration, and then blocked the photoperiod until birds entered the non-migratory wintering phase. We first performed de novo RNA-Sequencing from selected brain samples (hypothalamus) collected from birds at a standardised time at night, either in a migratory state (when restlessness was highest and at their body mass peak), or in a non-migratory state and conducted differential gene expression and functional pathways analyses. We found that the migratory state was associated with up-regulation of a few, yet functionally well defined, gene expression networks implicated in fat trafficking, protein and carbohydrate metabolism. Further analyses that focused on candidate genes (apolipoprotein H or APOH, lysosomal associated membrane protein-2 or LAMP2) from samples collected during the day or night across the entire study population suggested differences in the expression of these genes depending on the time of the day with the largest expression levels being found in the migratory birds sampled at night. We also found that expression of APOH was positively associated with levels of nocturnal activity in the migratory birds; such an association was absent within the non-migratory birds. Our results provide novel experimental evidence revealing that hypothalamic changes in expression of apolipoprotein pathways, which regulate the circulatory transport of lipids, are likely key regulatory activators of nocturnal migratory movements. Our study paves the way for performing deeper functional investigations on seasonal molecular remodelling underlying the development of the migratory phenotype.

Associations between the multitrajectory neuroplasticity of neuronavigated rTMS-mediated angular gyrus networks and brain gene expression in AD spectrum patients with sleep disorders.

The multifactorial influence of repetitive transcranial magnetic stimulation (rTMS) on neuroplasticity in neural networks is associated with improvements in cognitive dysfunction and sleep disorders. The mechanisms of rTMS and the transcriptional-neuronal correlation in Alzheimer's disease (AD) patients with sleep disorders have not been fully elucidated. Forty-six elderly participants with cognitive impairment (23 patients with low sleep quality and 23 patients with high sleep quality) underwent 4-week periods of neuronavigated rTMS of the angular gyrus and neuroimaging tests, and gene expression data for six post mortem brains were collected from another database. Transcription-neuroimaging association analysis was used to evaluate the effects on cognitive dysfunction and the underlying biological mechanisms involved. Distinct variable neuroplasticity in the anterior and posterior angular gyrus networks was detected in the low sleep quality group. These interactions were associated with multiple gene pathways, and the comprehensive effects were associated with improvements in episodic memory. Multitrajectory neuroplasticity is associated with complex biological mechanisms in AD-spectrum patients with sleep disorders. This was the first transcription-neuroimaging study to demonstrate that multitrajectory neuroplasticity in neural circuits was induced via neuronavigated rTMS, which was associated with complex gene expression in AD-spectrum patients with sleep disorders. The interactions between sleep quality and neuronavigated rTMS were coupled with multiple gene pathways and improvements in episodic memory. The present strategy for integrating neuroimaging, rTMS intervention, and genetic data provide a new approach to comprehending the biological mechanisms involved in AD.

Impacts on Atlantic Killifish from Neurotoxicants: Genes, Behavior, and Population-Relevant Outcomes.

Molecular, cellular, and organismal alterations are important descriptors of toxic effects, but our ability to extrapolate and predict ecological risks is limited by the availability of studies that link measurable end points to adverse population relevant outcomes such as cohort survival and growth. In this study, we used laboratory gene expression and behavior data from two populations of Atlantic killifish Fundulus heteroclitus [one reference site (SCOKF) and one PCB-contaminated site (NBHKF)] to inform individual-based models simulating cohort growth and survival from embryonic exposures to environmentally relevant concentrations of neurotoxicants. Methylmercury exposed SCOKF exhibited brain gene expression changes in the si:ch211-186j3.6, si:dkey-21c1.4, scamp1, and klhl6 genes, which coincided with changes in feeding and swimming behaviors, but our models simulated no growth or survival effects of exposures. PCB126-exposed SCOKF had lower physical activity levels coinciding with a general upregulation in nucleic and cellular brain gene sets (BGS) and downregulation in signaling, nucleic, and cellular BGS. The NBHKF, known to be tolerant to PCBs, had altered swimming behaviors that coincided with 98% fewer altered BGS. Our models simulated PCB126 decreased growth in SCOKF and survival in SCOKF and NBHKF. Overall, our study provides a unique demonstration linking molecular and behavioral data to develop quantitative, testable predictions of ecological risk.