Gene Expression In Brain Research Articles

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.

429 Maternal rate of gain and one-carbon metabolites supplementation alters the gene expression profile of fetal brain during early gestation in beef heifers

Abstract Maternal nutritional plane during pregnancy may leave lifelong impacts on offspring in beef cattle. Given that, we hypothesized that the supplementation of one-carbon metabolites (OCM) during pregnancy would mitigate the negative effects of maternal rate of gain through brain gene expression regulation in early developing bovine fetuses. The objective of this study was to evaluate the effects of OCM supplementation and maternal rate of gain on gene expression in the developing fetal brain in gestating beef heifers. Herein, Angus crossbred heifers (n = 72, body weight = 406 ± 33 kg) were randomly assigned to 2 × 2 factorial arrangement of treatments with two levels of maternal rate of gain (CON, 0.60 kg/d; and RES, -0.23 kg/d) each with or without OCM supplementation (+OCM, and -OCM). Heifers were fed individually and were bred using female-sexed semen from a single sire. The OCM supplementation included rumen-protected choline (44.4 g/d) and methionine (7.4 g/d) in corn carrier fed daily and weekly injections of folate (320 mg) and vitamin B12 (20 mg). The -OCM heifers received the corn carrier and saline injections. The treatments started at the time of breeding and continued until d 63 of gestation when pregnant heifers (n = 29) were slaughtered to collect fetal brain tissues for RNA sequencing. The fetal brain phenotypic data were analyzed using MIXED procedures of SAS, indicating that restricted nutrition affected the fetal right hemisphere weight (P &amp;lt; 0.05), and there was a strong tendency for overall fetal brain weight (0.05 &amp;lt; P &amp;lt; 0.1) to be affected as well. Brain transcriptomics data were analyzed using STAR aligner and a total of 177 differentially expressed genes (DEGs, FDR &amp;lt; 0.05) were identified across all treatment comparisons using DESeq2. Most of the DEGs were either isoforms of spliceosomal non-coding RNAs or micro-RNAs (miRNAs) associated with biological processes (FDR &amp;lt; 0.1) like mRNA processing, cellular nitrogen metabolism, lipid metabolism, and post-transcriptional gene silencing. The key miRNAs upregulated in the brain tissue of restricted fetuses without OCM supplementation, bta-mir-2375, bta-mir-876, and bta-mir-196a-1, were found to be associated with early embryogenesis and essential cellular regulatory processes. Conversely, in restricted fetuses with OCM supplementation, upregulated miRNAs such as bta-mir-216b, bta-mir-2285dd, and bta-mir-1298 were linked to early embryonic development, muscular development, and lipid metabolism in cattle. Both phenotypic and transcriptomics data here revealed that the maternal rate of gain altered fetal brain development, with differences seemingly compensated by OCM supplementation. USDA is an equal opportunity provider and employer.

Cortexa: a comprehensive resource for studying gene expression and alternative splicing in the murine brain

BackgroundGene expression and alternative splicing are strictly regulated processes that shape brain development and determine the cellular identity of differentiated neural cell populations. Despite the availability of multiple valuable datasets, many functional implications, especially those related to alternative splicing, remain poorly understood. Moreover, neuroscientists working primarily experimentally often lack the bioinformatics expertise required to process alternative splicing data and produce meaningful and interpretable results. Notably, re-analyzing publicly available datasets and integrating them with in-house data can provide substantial novel insights. However, such analyses necessitate developing harmonized data handling and processing pipelines which in turn require considerable computational resources and in-depth bioinformatics expertise.ResultsHere, we present Cortexa—a comprehensive web portal that incorporates RNA-sequencing datasets from the mouse cerebral cortex (longitudinal or cell-specific) and the hippocampus. Cortexa facilitates understandable visualization of the expression and alternative splicing patterns of individual genes. Our platform provides SplicePCA—a tool that allows users to integrate their alternative splicing dataset and compare it to cell-specific or developmental neocortical splicing patterns. All standardized gene expression and alternative splicing datasets can be downloaded for further in-depth downstream analysis without the need for extensive preprocessing.ConclusionsCortexa provides a robust and readily available resource for unraveling the complexity of gene expression and alternative splicing regulatory processes in the mouse brain. The data portal is available at https://cortexa-rna.com/

Identification and analysis correlation between hub genes and immune cell infiltration related to LPS-induced cognitive impairment

BackgroundThe occurrence of immunity and inflammation outside the central nervous system frequently results in acute cognitive impairment among elderly patients. However, there is currently a lack of standardized methods for diagnosing acute cognitive impairment. The objective of our study was to identify potential mRNA biomarkers and investigate the pathogenesis of acute cognitive impairment in mice brains. MethodsTo analyze changes in hub genes associated with acute cognitive impairment, bioinformatics analysis was performed on the mouse brain injury data of sterile saline control group and lipopolysaccharide (LPS) induced experimental group in Gene Expression Omnibus (GEO). Functional analysis was conducted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), which facilitated to identify some potential mRNA biomarkers for hub gene expression in mice brains. Additionally, the "CIBERSORT X″ R kit was employed to examine immune cell infiltrations of mice brains in LPS group and saline group. ResultsIn the LPS and saline group, 102 significantly upregulated differentially expressed genes (DEGs) and 32 downregulated DEGs were identified. The pathway enrichment analysis using GO and KEGG revealed that these DEGs were mainly related to the regulation of cytokine, cytokine-cytokine receptor interaction, as well as protein interaction with cytokine and cytokine receptor. Immune cell infiltration analysis indicated potential involvement of M1 macrophages, NK cells resting, T cells CD4 memory, and T cells CD8 naive in the process of cognitive impairment. By constructing a protein-protein interaction (PPI) network, five hub genes (Cxcl10, Cxcl12, Cxcr3, Gbp2, and Ifih1) showed significant associations with immune cell types by using a threshold Spearman's rank correlation coefficient of R > 0.50 and p < 0.05. ConclusionThe mRNA expression profile of the mice brain tissues in the LPS group differed from that in the normal saline group. These significantly expressed mRNAs may act an importance in the pathogenesis of acute cognitive impairment through mechanisms involving immunity and neuroinflammation.

Systemic inflammation following traumatic injury and its impact on neuroinflammatory gene expression in the rodent brain

BackgroundTrauma can result in systemic inflammation that leads to organ dysfunction, but the impact on the brain, particularly following extracranial insults, has been largely overlooked.MethodsBuilding upon our prior findings, we aimed to understand the impact of systemic inflammation on neuroinflammatory gene transcripts in eight brain regions in rats exposed to (1) blast overpressure exposure [BOP], (2) cutaneous thermal injury [BU], (3) complex extremity injury, 3 hours (h) of tourniquet-induced ischemia, and hind limb amputation [CEI+tI+HLA], (4) BOP+BU or (5) BOP+CEI and delayed HLA [BOP+CEI+dHLA] at 6, 24, and 168 h post-injury (hpi).ResultsGlobally, the number and magnitude of differentially expressed genes (DEGs) correlated with injury severity, systemic inflammation markers, and end-organ damage, driven by several chemokines/cytokines (Csf3, Cxcr2, Il16, and Tgfb2), neurosteroids/prostaglandins (Cyp19a1, Ptger2, and Ptger3), and markers of neurodegeneration (Gfap, Grin2b, and Homer1). Regional neuroinflammatory activity was least impacted following BOP. Non-blast trauma (in the BU and CEI+tI+HLA groups) contributed to an earlier, robust and diverse neuroinflammatory response across brain regions (up to 2–50-fold greater than that in the BOP group), while combined trauma (in the BOP+CEI+dHLA group) significantly advanced neuroinflammation in all regions except for the cerebellum. In contrast, BOP+BU resulted in differential activity of several critical neuroinflammatory-neurodegenerative markers compared to BU. t-SNE plots of DEGs demonstrated that the onset, extent, and duration of the inflammatory response are brain region dependent. Regardless of injury type, the thalamus and hypothalamus, which are critical for maintaining homeostasis, had the most DEGs. Our results indicate that neuroinflammation in all groups progressively increased or remained at peak levels over the study duration, while markers of end-organ dysfunction decreased or otherwise resolved.ConclusionsCollectively, these findings emphasize the brain's sensitivity to mediators of systemic inflammation and provide an example of immune-brain crosstalk. Follow-on molecular and behavioral investigations are warranted to understand the short- to long-term pathophysiological consequences on the brain, particularly the mechanism of blood–brain barrier breakdown, immune cell penetration–activation, and microglial activation.

Microglia are not necessary for maintenance of blood-brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism

Microglia, the resident immune cells of the central nervous system, are intimately involved in the brain's most basic processes, from pruning neural synapses during development to preventing excessive neuronal activity throughout life. Studies have reported both helpful and harmful roles for microglia at the blood-brain barrier (BBB) in the context of disease. However, less is known about microglia-endothelial cell interactions in the healthy brain. To investigate the role of microglia at a healthy BBB, we used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia and analyzed the BBB ultrastructure, permeability, and transcriptome. Interestingly, we found that, despite their direct contact with endothelial cells, microglia are not necessary for the maintenance of BBB structure, function, or gene expression in the healthy brain. However, we found that PLX5622 treatment alters brain endothelial cholesterol metabolism. This effect was independent from microglial depletion, suggesting that PLX5622 has off-target effects on brain vasculature.

A gut reaction? The role of the microbiome in aggression

Recent research has unveiled conflicting evidence regarding the link between aggression and the gut microbiome. Here, we compared behavior profiles of control, germ-free (GF), and antibiotic-treated mice, as well as re-colonized GF mice to understand the impact of the gut microbiome on aggression using the resident-intruder paradigm. Our findings revealed a link between gut microbiome depletion and higher aggression, accompanied by notable changes in urine metabolite profiles and brain gene expression. This study extends beyond classical murine models to humanized mice to reveal the clinical relevance of early-life antibiotic use on aggression. Fecal microbiome transplant from infants exposed to antibiotics in early life (and sampled one month later) into mice led to increased aggression compared to mice receiving transplants from unexposed infants. This study sheds light on the role of the gut microbiome in modulating aggression and highlights its potential avenues of action, offering insights for development of therapeutic strategies for aggression-related disorders.

IBS stress reactivity phenotype is associated with blood transcriptome profiles and microstructural and functional brain changes.

Clinical evidence suggests significant interindividual differences in stress reactivity (SR), but biological mechanisms and therapeutic implications of these differences are poorly understood. We aimed to identify the biological basis of increased SR by investigating associations between a psychometric-based phenotype with blood transcriptomics profiles of increased sympathetic nervous system (SNS) activation and brain imaging phenotypes in irritable bowel syndrome (IBS) participants and healthy controls (HCs). A cross-sectional observational study design, transcriptomics profiling, multimodal brain imaging, and psychosocial assessments were obtained in 291 female and male IBS participants and HCs. Prior to analyses, unsupervised clustering was applied to derive high and low SR subgroups across participants based on two measures of SR. General linear models tested for SR group differences in clinical and biological parameters. Exploratory analyses examined associations between SR group-specific brain alterations and gene expression. The high, compared to low SR group showed greater cyclic AMP response element-binding protein (CREB) gene expression consistent with tonic SNS activity and proinflammatory changes in whole blood. Brain imaging showed neuroplastic changes in the high SR group consistent with an upregulation of ascending arousal systems and sensory processing and integration regions, and functional connectivity changes in the central autonomic network. SR moderated the sex difference in extraintestinal symptoms. The findings support a model of tonically increased SNS activity as a plausible risk factor for increased autonomic reactivity to psychosocial stressors and low grade immune activation in both IBS and HCs, with a greater prevalence in IBS. These findings may have important implications for personalized treatment interventions in IBS.

Transcriptional expression patterns of the cortical morphometric similarity network in progressive supranuclear palsy.

It has been demonstrated that progressive supranuclear palsy (PSP) correlates with structural abnormalities in several distinct regions of the brain. However, whether there are changes in the morphological similarity network (MSN) and the relationship between changes in brain structure and gene expression remain largely unknown. We used two independent cohorts (discovery dataset: PSP: 51, healthy controls (HC): 82; replication dataset: PSP: 53, HC: 55) for MSN analysis and comparing the longitudinal changes in the MSN of PSP. Then, we applied partial least squares regression to determine the relationships between changes in MSN and spatial transcriptional features and identified specific genes associated with MSN differences in PSP. We further investigated the biological processes enriched in PSP-associated genes and the cellular characteristics of these genes, and finally, we performed an exploratory analysis of the relationship between MSN changes and neurotransmitter receptors. We found that the MSN in PSP patients was mainly decreased in the frontal and temporal cortex but increased in the occipital cortical region. This difference is replicable. In longitudinal studies, MSN differences are mainly manifested in the frontal and parietal regions. Furthermore, the expression pattern associated with MSN changes in PSP involves genes implicated in astrocytes and excitatory and inhibitory neurons and is functionally enriched in neuron-specific biological processes related to synaptic signaling. Finally, we found that the changes in MSN were mainly negatively correlated with the levels of serotonin, norepinephrine, and opioid receptors. These results have enhanced our understanding of the microscale genetic and cellular mechanisms responsible for large-scale morphological abnormalities in PSP patients, suggesting potential targets for future therapeutic trials.

Structural and molecular alterations in murine tissue due to far-field radiofrequency exposure

Public concern over exposure to radiofrequency electromagnetic fields has prompted several studies to determine possible health outcomes. However, studies on low level far-field radiofrequency (RF) exposure remain inconclusive on whether it can alter biological systems. Our study's aim was to evaluate structural and molecular modifications such as apoptosis and gene expression in murine brain, liver and kidney tissues exposed to a far-field RF of 915 MHz at a whole-body specific absorption rate of 1.17 W/kg. Forty (40) Swiss male mice were equally and randomly divided into 2 groups: a control group and an RF-exposed group. Each were further equally subdivided (n=5 per subgroup) based on different time points: baseline or no exposure, 3-day exposure, 6-day-exposure and 9-day exposure subgroups. Biometric parameters such as body temperature, body weight, and organ weight were obtained. Tissue samples were collected and analyzed using light and electron microscopy, followed by qPCR assay for both the p53 and Hsp-70 genes. Statistical analysis was performed using ANOVA. There was evidence of both structural and molecular modification beginning Day 3 from continuous-wave far-field RF exposure. The study established multi-level alterations in the murine system due to far field RF exposure providing a glimpse of possible biological effects, and therefore, a need for further studies to translate such evidence in a larger biological perspective.

Cell-type-specific effects of autism-associated 15q duplication syndrome in the human brain

Recurrent copy-number variation represents one of the most well-established genetic drivers in neurodevelopmental disorders, including autism spectrum disorder. Duplication of 15q11-q13 (dup15q) is a well-described neurodevelopmental syndrome that increases the risk of autism more than 40-fold. However, the effects of this duplication on gene expression and chromatin accessibility in specific cell types in the human brain remain unknown. To identify the cell-type-specific transcriptional and epigenetic effects of dup15q in the human frontal cortex, we conducted single-nucleus RNA sequencing and multi-omic sequencing on dup15q-affected individuals (n= 6) as well as individuals with non-dup15q autism (n= 7) and neurotypical control individuals (n= 7). Cell-type-specific differential expression analysis identified significantly regulated genes, critical biological pathways, and differentially accessible genomic regions. Although there was overall increased gene expression across the duplicated genomic region, cellular identity represented an important factor mediating gene-expression changes. As compared to other cell types, neuronal subtypes showed greater upregulation of gene expression across a critical region within the duplication. Genes that fell within the duplicated region and had high baseline expression in control individuals showed only modest changes in dup15q, regardless of cell type. Of note, dup15q and autism had largely distinct signatures of chromatin accessibility but shared the majority of transcriptional regulatory motifs, suggesting convergent biological pathways. However, the transcriptional binding-factor motifs implicated in each condition implicated distinct biological mechanisms: neuronal JUN and FOS networks in autism vs. an inflammatory transcriptional network in dup15q microglia. This work provides a cell-type-specific analysis of how dup15q changes gene expression and chromatin accessibility in the human brain, and it finds evidence of marked cell-type-specific effects of this genetic driver. These findings have implications for guiding therapeutic development in dup15q syndrome, as well as understanding the functional effects of copy-number variants more broadly in neurodevelopmental disorders.

Effects of gestational hypothyroidism on mouse brain development: Gabaergic systems and oxidative stress

Hormonal imbalance during pregnancy is a risk factor for neuropsychiatric impairment in the offspring. It has been suggested that hypothyroidism leads to dysfunction of cortical GABAergic interneurons and inhibitory system development that in turn underlies impairment of the central nervous system. Here we investigated how gestational hypothyroidism affected offspring GABAergic system development as well as redox regulation parameters, because of previous links identified between the two. Experimental Gestational Hypothyroidism (EGH) was induced in CD-1 mice with 0.02% methimazole (MMI) in drinking water from embryonic day 9 (E9) until tissue collection at embryonic day 14 (E14) or E18. We examined GABAergic cell distribution and inhibitory system development gene expression as well as redox relevant gene expression and direct measures across all embryos regardless of sex. Intrauterine restriction of maternal thyroid hormones significantly impacted both of these outcomes in brain, as well as altering redox regulation in the placenta. GAD67+ neuronal migration was reduced, accompanied by a disruption in gene expression influencing GABAergic cell migration and cortical inhibitory neural system development. EGH also altered embryonic brain gene expression of Gpx1, Nfe2l2, Cat levels in the dorsal E14 brains. Additionally, EGH resulted in elevated TBARS, Gpx1 and Nfe2l2 in the ventral E18 brains. Furthermore, EGH downregulated placental Gpx1 gene expression at E14 and increased protein oxidation at E18. These findings support the hypothesis that sufficient maternal thyroid hormone supply to the fetus influences central nervous system development, including processes of GABAergic system development and redox equilibrium.

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

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. Here, we employed mouse model and spatial transcriptomics and single-nucleus multi-omics approaches to investigate the impact of high maternal FA supplementation during the periconceptional period on offspring brain development. 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. Our findings provide new insights into specific brain regions, cell types, gene expressions and pathways that can be affected by maternal high FA supplementation.

Beneficial Effects of Manilkara zapota-Derived Bioactive Compounds in the Epigenetic Program of Neurodevelopment.

Gestational diet has a long-dated effect not only on the disease risk in offspring but also on the occurrence of future neurological diseases. During ontogeny, changes in the epigenetic state that shape morphological and functional differentiation of several brain areas can affect embryonic fetal development. Many epigenetic mechanisms such as DNA methylation and hydroxymethylation, histone modifications, chromatin remodeling, and non-coding RNAs control brain gene expression, both in the course of neurodevelopment and in adult brain cognitive functions. Epigenetic alterations have been linked to neuro-evolutionary disorders with intellectual disability, plasticity, and memory and synaptic learning disorders. Epigenetic processes act specifically, affecting different regions based on the accessibility of chromatin and cell-specific states, facilitating the establishment of lost balance. Recent insights have underscored the interplay between epigenetic enzymes active during embryonic development and the presence of bioactive compounds, such as vitamins and polyphenols. The fruit of Manilkara zapota contains a rich array of these bioactive compounds, which are renowned for their beneficial properties for health. In this review, we delve into the action of each bioactive micronutrient found in Manilkara zapota, elucidating their roles in those epigenetic mechanisms crucial for neuronal development and programming. Through a comprehensive understanding of these interactions, we aim to shed light on potential avenues for harnessing dietary interventions to promote optimal neurodevelopment and mitigate the risk of neurological disorders.

Mate choice in the brain: species differ in how male traits 'turn on' gene expression in female brains.

Mate choice plays a fundamental role in speciation, yet we know little about the molecular mechanisms that underpin this crucial decision-making process. Stickleback fish differentially adapted to limnetic and benthic habitats are reproductively isolated and females of each species use different male traits to evaluate prospective partners and reject heterospecific males. Here, we integrate behavioural data from a mate choice experiment with gene expression profiles from the brains of females actively deciding whether to mate. We find substantial gene expression variation between limnetic and benthic females, regardless of behavioural context, suggesting general divergence in constitutive gene expression patterns, corresponding to their genetic differentiation. Intriguingly, female gene co-expression modules covary with male display traits but in opposing directions for sympatric populations of the two species, suggesting male displays elicit a dynamic neurogenomic response that reflects known differences in female preferences. Furthermore, we confirm the role of numerous candidate genes previously implicated in female mate choice in other species, suggesting evolutionary tinkering with these conserved molecular processes to generatedivergent mate preferences. Taken together, our study adds important new insights to our understanding of the molecular processes underlying female decision-making critical for generating sexual isolation and speciation.

Molecular, Biochemical and Histological Assessment in Paraquat Induced Neurotoxicity: Restoring Role of Nano-curcumin in an Experimental Study

Abstract Background: Paraquat (PQ) is known to cause damage to various organs, including the brain. Although curcumin have anti-inflammatory and anti-oxidant properties, it is not yet clear how they relate to PQ-induced neurotoxicity. This study’s objective was to compare the effects of curcumin and nanocurcumin on PQ-induced neurotoxicity in male rats. Methods: 36 rats were randomly divided into 6 groups. control subjects and animals poisoned with PQ that received treatment with or without curcumin and nano-curcumin for 7 days. The brain tissues were collected at the end of this period. Total antioxidant capacity (TAC), lipid peroxidation (LPO), and total thiol groups (TTG) were assessed by using spectrophotometry. Moreover, the histopathology of brain and antioxidant gene expression were assessed by biochemical and reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Results: Curcumin and nanocurcumin therapy alleviated the PQ-triggered oxidative stress in brain tissue by raising the levels of anti-oxidant biomarkers like TAC and TTG, up-regulating the expression of Nrf2, HO-1, and NQO-1, reducing the levels of oxidative stress indices like LPO, and down- regulating the expression of Keap-1 in brain tissue. Conclusions: Treatment with curcumin and nano-curcumin improves brain function in PQ toxicity and nanocurcumin was more advantageous than ordinary curcumin.