Gene Expression In Brain Research Articles

Prediction and Identification of Signature Genes Expressed in Different Brain Regions through RNA-Seq Data Analysis

Brain is one of the most intricate organs in the human body that works with billions of cells. A brain tumor emerges when there is uncontrolled division of cells shaping a strange gathering of cells around or inside the cerebrum. To understand the complexity of brain function and gene expression in different regions of brain is most challenging and crucial. RNAseq techniques along with computational analysis has made this task much easier and accurate. In this current research RNAseq data of brain regions have been used to predict functional genes in different regions of brains. Differential expression of genes in different regions of brain highlights the function of genes and associated pathways in brain function. The aim of this study was to identify differentially expressed gene in the brain tumor samples. RNA-seq data was retrieved from ENA database with the accession no.- PRJNA294929. Total 5 samples were retrieved in fastq format, out of which 4 samples were of corpous callosum and 1 sample was of frontal cortex. Differentially Expressed Genes (DEG) analysis was done using Galaxy platform and R software, functional enrichment of DEGs was done using DAVID and GO databases. The RNA-seq data analysis shows the up regulation of PHGDH, TUBB4A, HSPA2, GFAP, NKX3-1, COX3 genes and three genes PHGDH, COX3 and MT3 shows significant difference in their gene expression. This result can have importance in understanding the complexity of brain transcriptomics and DEGs can be further studied to evaluate their expression in brain cells and associated diseases. Further wet lab verification is required as these genes can be used as potential drug target and can be used for drug designing for brain tumor.

Effect of tramadol hydrochloride on neural tube development in 48-hr chick embryos: Argyrophilic nucleolar organizing region and genetic analysis study.

Tramadol hydrochloride or tramadol is an opioid analgesic that acts on the central nervous system. The pregnancy category of tramadol is determined as "C" according to the Food and Drug Administration. There are no adequate and well-controlled studies in pregnant women. In this study, we aimed to reveal the effects of tramadol on neural tube (midline) closure by analyzing morphologically, histologically and genetically in chick embryos. Ninety White Leghorn species, fertile and 0-day-old specific pathogen-free eggs (60 ± 5g) were used in the study. Eggs were divided into a total of six groups (control, sham, and drug groups). Four different doses of tramadol (1, 2.5, 5, and 7.5mg/egg) were administered subblastodermically at the 28th hour of the incubation. All eggs were opened at the 48th hour of incubation and evaluated. Embryos in the control group according to Hamburger-Hamilton classification were compatible with stages 13 and 14. In the groups treated with tramadol, it was determined that the embryos had neural tube closure defects (such as neck, tail regions) and some embryos showed developmental retardation due to the increase in the drug dose. In the statistical analysis performed, a significant difference was found between the control group and the group receiving the highest dose of tramadol in terms of crown-rump length and number of somites (p< .05). The brain and reproductive expression gene expression was upregulated in embryos at each of tramadol doses compared to control group. It was determined that tramadol causes neural tube closure defects in embryos depending on the dose.

Artificial intelligence-driven meta-analysis of brain gene expression identifies novel gene candidates and a role for mitochondria in Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of dementia. There is no treatment and AD models have focused on a small subset of genes identified in familial AD. Microarray studies have identified thousands of dysregulated genes in the brains of patients with AD yet identifying the best gene candidates to both model and treat AD remains a challenge. We performed a meta-analysis of microarray data from the frontal cortex (n = 697) and cerebellum (n = 230) of AD patients and healthy controls. A two-stage artificial intelligence approach, with both unsupervised and supervised machine learning, combined with a functional network analysis was used to identify functionally connected and biologically relevant novel gene candidates in AD. We found that in the frontal cortex, genes involved in mitochondrial energy, ATP, and oxidative phosphorylation, were the most significant dysregulated genes. In the cerebellum, dysregulated genes were involved in mitochondrial cellular biosynthesis (mitochondrial ribosomes). Although there was little overlap between dysregulated genes between the frontal cortex and cerebellum, machine learning models comprised of this overlap. A further functional network analysis of these genes identified that two downregulated genes, ATP5L and ATP5H, which both encode subunits of ATP synthase (mitochondrial complex V) may play a role in AD. Combined, our results suggest that mitochondrial dysfunction, particularly a deficit in energy homeostasis, may play an important role in AD.

Cell-Specific Gene Expression in the Prenatal Brain and Schizophrenia Risk

While a variety of evidence supports a prenatal component to schizophrenia, the relevant cell types of the developing brain have, to date, been unclear. To explore cellular mediators of schizophrenia genetic risk in early brain development, Cameron et al. (1), in the current issue of Biological Psychiatry, applied single-nuclei RNA sequencing (snRNA-seq) technology and analyses to 5 regions of the human prenatal brain and combined this with the latest data from gene discovery for the condition from both a genome-wide association study (GWAS) (2) and an exome sequencing study (3).

Opioid medication use and blood DNA methylation: epigenome-wide association meta-analysis.

Aim: To identify differential methylation related to prescribed opioid use. Methods: This study examined whether blood DNA methylation, measured using Illumina arrays, differs by recent opioid medication use in four population-based cohorts. We meta-analyzed results (282 users; 10,560 nonusers) using inverse-variance weighting. Results: Differential methylation (false discovery rate <0.05) was observed at six CpGs annotated to the following genes: KIAA0226, CPLX2, TDRP, RNF38, TTC23 and GPR179. Integrative epigenomic analyses linked implicated loci to regulatory elements in blood and/or brain. Additionally, 74 CpGs were differentially methylated in males or females. Methylation at significant CpGs correlated with gene expression in blood and/or brain. Conclusion: This study identified DNA methylation related to opioid medication use in general populations. The results could inform the development of blood methylation biomarkers of opioid use.

Transcriptomic Differences in Endothelial Cells Across Five Brain Regions in Normal Aging and Alzheimer's Disease

AbstractBackgroundAltered cerebral vasculature is recognized as a key feature of Alzheimer’s disease (AD) neuropathology, with current evidence suggesting a diverse collection of changes including aberrant angiogenesis, vascular pruning, inflammation, senescence, and other remodeling events. Previous studies examining the endothelial cell transcriptome in AD have been limited to 1‐2 brain regions and hampered by low numbers of isolated endothelial cell nuclei, potentially missing relevant regional heterogeneity. We hypothesized that such regional heterogeneity in endothelial cell gene expression in the normal aging brain may contribute to the varied vascular responses to AD neuropathology.MethodNuclei were isolated from five brain areas in subjects with increasing AD pathology (n=32 donors). The five brain areas chosen represent the hierarchical accumulation of tau pathology in AD: entorhinal cortex &gt; inferior temporal gyrus &gt; prefrontal cortex &gt; secondary visual cortex &gt; primary visual cortex. All subjects had detailed p‐tau, in vitro tau seeding, and amyloid‐beta plaque measurements available. Nuclei were FACS sorted to exclude NeuN+ and Olig2+ cells, and the resulting neuron‐ and oligodendrocyte‐depleted fraction was subject to single‐nucleus RNAseq. Endothelial cell nuclei were identified based on high von Willebrand factor expression and filtered to exclude contaminating glia, yielding a dataset comprised of 51,586 total nuclei.ResultTranscriptomic analysis confirmed that endothelial cells share a core set of commonly upregulated genes across the five brain regions compared to other cell types. However, there is also regional heterogeneity with 193‐311 differentially upregulated genes expressed in endothelial cells within each brain area relative to all other areas. Compared to normal aging brain, endothelial cells from AD donors downregulated 962 genes and upregulated 936 genes that are enriched in vasculogenesis, blood‐brain barrier maintenance, senescence, and leukocyte interactions. Further analysis indicates regional differences in upregulation of these pathways and highlights the relationship to disease burden.ConclusionThis dataset demonstrates a previously unrecognized regional heterogeneity in endothelial cell transcriptome in the normal aging human brain. These regional differences may impact the endothelial cell response to the local AD pathology. This dataset will inform ongoing research efforts to unravel the molecular underpinnings of AD‐induced endothelial cell dysfunction.

Complement C3 Lowering in Adult Inducible Conditional Knockout Mice: Long‐Lasting Effects

AbstractBackgroundComplement C3, a central component of the complement cascade, participates in synaptic elimination during brain development and is elevated in the brain with aging and Alzheimer’s disease (AD). Germline C3 knockout (KO) protects against age‐ and AD‐related hippocampal synapse loss and functional decline (Shi Q et al., J Neurosci 2015; Shi Q et al., Sci Transl Med 2017). We crossed C3fl/fl mice with Rosa26‐Cre‐ERT2 mice to generate global C3 inducible conditional KO mice (C3iKO). Previously, we reported that 5 daily TAM treatments in C3iKO mice at 4‐5 mo of age led to sustained C3 reductions of ∼95% in serum and ∼80% in brain, and protected mice against age‐related cognitive decline at 16‐17 months. In addition, TAM treatment at 3‐4 mo of age protected long‐term potentiation (LTP) in hippocampal slices exposed to toxic Aβ dimers (S26C) obtained at 7‐8 mo of age. Here, we extend our analyses to include changes in complement, cytokine and ApoE expression in these same C3iKO mice and provide confirmatory results in a second cohort of mice.MethodqRT‐PCR was used to quantify brain gene expression in the first cohort. In the second cohort, C3iKO, C3fl/fl and C3KO mice were treated with TAM or corn oil (CO) at 7‐8 mo of age. Cognitive testing commenced at 17‐18 mo and included the Spatial Novelty Y Maze (SPNY), Novel Object Recognition (NOR) and Displaced Object Recognition (DOR). Mice were euthanized and hippocampal synaptosomes isolated for Western blot analysis.ResultOne‐year post‐treatment, C1qa, C1qb, C1qc, C3, CD11b, CD18, IL‐1β, IFNα, IFNβ, and APOE mRNAs were reduced, and TGFβ and TGFβR1 mRNAs were elevated in brains of TAM‐treated C3iKO and C3KO mice compared to CO‐treated C3iKO mice. In the second cohort, C3 protein levels were reduced ∼92% in serum and ∼77% in hippocampal synaptosomes in TAM‐treated C3iKO mice. TAM‐treated C3iKO mice and both C3KO groups showed significantly better performance in SNYM, LOR and DOR tests compared to controls, consistent with our first study. Pre‐ and post‐synaptic markers were elevated in TAM‐treated vs. CO‐treated C3iKO hippocampal synaptosomes.ConclusionGlobal C3 lowering in adulthood has long‐lasting effects on immune signaling and hippocampal function. (NIH RF1 AG060057‐CAL)

Long-term effects of prophylactic MgSO4 in maternal immune activation rodent model at adolescence and adulthood.

The effects of MgSO4 as an anti-inflammatory agent in pregnant women have been investigated in the last few years. Infections can cause an inflammatory reaction involving the placenta membranes and amniotic cavity. They may have short-term effects on the mother and her fetuses, like preterm birth, cerebral palsy, and developmental delay. Despite the alleged advantages of MgSO4 as a neuroprotective agent in the preterm brain, the long-term molecular and behavioral function of MgSO4 has not been fully elucidated. Here, we investigated the long-term effect of antenatal MgSO4 , during late gestation, on offspring's behavior focusing on cognitive function, motor activity, and social cognition in adolescence and adulthood, and explored its influence on brain gene expression (e.g., ErbB signaling, pro-inflammatory, and dopaminergic markers) in adulthood. A significant abnormal exploratory behavior of offspring of MgSO4 -treated dams was found compared to the control group in both adolescence and adulthood. Furthermore, we found that adult females exposed to MgSO4 under inflammation displayed working and recognition memory impairment. A reduction in IL-6 expression was detected in the prefrontal cortex, and hippocampus specimens derived from LPS-Mg-treated group. In contrast, an imbalanced expression of dopamine 1 and 2 receptors was detected only in prefrontal cortex specimens. Besides, we found that MgSO4 ameliorated the overexpression of the Nrg1 and Erbb4 receptors induced by LPS in the hippocampus. Thus, MgSO4 treatment for preventing brain injuries can adversely affect offspring cognition behavior later in life, depending on the sex and age of the offspring.

New insights into glioma frequency maps: From genetic and transcriptomic correlate to survival prediction.

Increasing evidence indicates that glioma topographic location is linked to the cellular origin, molecular alterations and genetic profile. This research aims to (a) reveal the underlying mechanisms of tumor location predilection in glioblastoma multiforme (GBM) and lower-grade glioma (LGG) and (b) leverage glioma location features to predict prognosis. MRI images from 396 GBM and 190 LGG (115 astrocytoma and 75 oligodendroglioma) patients were standardized to construct frequency maps and analyzed by voxel-based lesion-symptom mapping. We then investigated the spatial correlation between glioma distribution with gene expression in healthy brains. We also evaluated transcriptomic differences in tumor tissue from predilection and nonpredilection sites. Furthermore, we quantitively characterized tumor anatomical localization and explored whether it was significantly related to overall survival. Finally, we employed a support vector machine to build a survival prediction model for GBM patients. GBMs exhibited a distinct location predilection from LGGs. GBMs were nearer to the subventricular zone and more likely to be localized to regions enriched with synaptic signaling, whereas astrocytoma and oligodendroglioma tended to occur in areas associated with the immune response. Synapse, neurotransmitters and calcium ion channel-related genes were all activated in GBM tissues coming from predilection regions. Furthermore, we characterized tumor location features in terms of a series of tumor-to-predilection distance metrics, which were able to predict GBM 1-year survival status with an accuracy of 0.71. These findings provide new perspectives on our understanding of tumor anatomic localization. The spatial features of glioma are of great value in individual therapy and prognosis prediction.

Development and metamorphosis in frogs deficient in the thyroid hormone transporter MCT8

Precisely regulated thyroid hormone (TH) signaling within tissues during frog metamorphosis gives rise to the organism-wide coordination of developmental events among organs required for survival. This TH signaling is controlled by multiple cellular mechanisms, including TH transport across the plasma membrane. A highly specific TH transporter has been identified, namely monocarboxylate transporter 8 (MCT8), which facilitates uptake and efflux of TH and is differentially and dynamically expressed among tissues during metamorphosis. We hypothesized that loss of MCT8 would alter tissue sensitivity to TH and affect the timing of tissue transformation. To address this, we used CRISPR/Cas9 to introduce frameshift mutations inslc16a2, the gene encoding MCT8, inXenopus laevis. We produced homozygous mutant tadpoles with a 29-bp mutation in the l-chromosome and a 20-bp mutation in the S-chromosome. We found that MCT8 mutants survive metamorphosis with normal growth and development of external morphology throughout the larval period. Consistent with this result, the expression of the pituitary hormone regulating TH plasma levels (tshb) was similar among genotypes as was TH response gene expression in brain at metamorphic climax. Further, delayed initiation of limb outgrowth during natural metamorphosis and reduced hindlimb and tail TH sensitivity were not observed in MCT8 mutants. In sum, we did not observe an effect on TH-dependent development in MCT8 mutants, suggesting compensatory TH transport occurs in tadpole tissues, as seen in most tissues in all model organisms examined.

Gene expression in the female tree swallow brain is associated with inter- and intra-population variation in glucocorticoid levels

Studies of the evolutionary causes and consequences of variation in circulating glucocorticoids (GCs) have begun to reveal how they are shaped by selection. Yet the extent to which variation in circulating hormones reflects variation in other important regulators of the hypothalamic-pituitary-adrenal (HPA) axis, and whether these relationships vary among populations inhabiting different environments, remain poorly studied. Here, we compare gene expression in the brain of female tree swallows (Tachycineta bicolor) from populations that breed in environments that differ in their unpredictability. We find evidence of inter-population variation in the expression of glucocorticoid and mineralocorticoid receptors in the hypothalamus, with the highest gene expression in a population from an extreme environment, and lower expression in a population from a more consistent environment as well as in birds breeding at an environmentally variable high-altitude site that are part of a population that inhabits a mixture of high and low altitude habitats. Within some populations, variation in circulating GCs predicted differences in gene expression, particularly in the hypothalamus. However, some patterns were present in all populations, whereas others were not. These results are consistent with the idea that some combination of local adaptation and phenotypic plasticity may modify components of the HPA axis affecting stress resilience. Our results also underscore that a comprehensive understanding of the function and evolution of the stress response cannot be gained from measuring circulating hormones alone, and that future studies that apply a more explicitly evolutionary approach to important regulatory traits are likely to provide significant insights.

Systematic investigation of imprinted gene expression and enrichment in the mouse brain explored at single-cell resolution

BackgroundAlthough a number of imprinted genes are known to be highly expressed in the brain, and in certain brain regions in particular, whether they are truly over-represented in the brain has never been formally tested. Using thirteen single-cell RNA sequencing datasets we systematically investigated imprinted gene over-representation at the organ, brain region, and cell-specific levels.ResultsWe established that imprinted genes are indeed over-represented in the adult brain, and in neurons particularly compared to other brain cell-types. We then examined brain-wide datasets to test enrichment within distinct brain regions and neuron subpopulations and demonstrated over-representation of imprinted genes in the hypothalamus, ventral midbrain, pons and medulla. Finally, using datasets focusing on these regions of enrichment, we identified hypothalamic neuroendocrine populations and the monoaminergic hindbrain neurons as specific hotspots of imprinted gene expression.ConclusionsThese analyses provide the first robust assessment of the neural systems on which imprinted genes converge. Moreover, the unbiased approach, with each analysis informed by the findings of the previous level, permits highly informed inferences about the functions on which imprinted gene expression converges. Our findings indicate the neuronal regulation of motivated behaviours such as feeding and sleep, alongside the regulation of pituitary function, as functional hotspots for imprinting. This adds statistical rigour to prior assumptions and provides testable predictions for novel neural and behavioural phenotypes associated with specific genes and imprinted gene networks. In turn, this work sheds further light on the potential evolutionary drivers of genomic imprinting in the brain.

Matrix-assisted laser desorption/ionization analysis of the brain proteome of microgravity-exposed mice from the International Space Station

Manned spaceflight exposes humans to extreme environmental conditions, including microgravity exposures. The effects of microgravity during spaceflight could lead to changes in brain structure, gene expression, and vascular physiology. Given the known physiological effects, it is highly likely that there are microgravity-initiated proteomic differentials in the brain, possibly domain specific. MALDI-TOF (matrix-assisted laser desorption/ionization time of flight) Imaging Mass Spectrometry allows the visualization of the spatial distribution of highly abundant intact proteins in tissue specimens. This study utilized this technique to visualize global proteomic changes induced by microgravity exposure in brain tissue received from the Rodent Research-1 Center for the Advancement of Science in Space (CASIS)/National Aeronautics and Space Administration (NASA). Proteome profiles were obtained from isolated whole brain tissue from microgravity exposed, Habitat control, and baseline. While a total of 135 mass peaks equating to individual proteins were identified, statistical analysis determined that there were no significant differences in the spectra profiles from the three test groups utilizing this methodology, possibly due to sample collection logistics rather than lack of cellular response.

Thyroid hormone elicits intergenerational epigenetic effects on adult social behavior and fetal brain expression of autism susceptibility genes.

Genetic mutations identified in genome-wide association studies can only explain a small percentage of the cases of complex, highly heritable human conditions, including neurological and neurodevelopmental disorders. This suggests that intergenerational epigenetic effects, possibly triggered by environmental circumstances, may contribute to their etiology. We previously described altered DNA methylation signatures in the sperm of mice that experienced developmental overexposure to thyroid hormones as a result of a genetic defect in hormone clearance (DIO3 deficiency). Here we studied fetal brain gene expression and adult social behavior in genetically normal F2 generation descendants of overexposed mice. The brain of F2 generation E13.5 fetuses exhibited abnormal expression of genes associated with autism in humans, including Auts2, Disc1, Ldlr, Per2, Shank3, Oxtr, Igf1, Foxg1, Cd38, Grid2, Nrxn3, and Reln. These abnormal gene expression profiles differed depending on the sex of the exposed ancestor. In the three-chamber social box test, adult F2 generation males manifested significantly decreased interest in social interaction and social novelty, as revealed by decrease total time, distance traveled and time immobile in the area of interaction with novel strangers. F1 generation mice, compared to appropriate controls also exhibited altered profiles in fetal brain gene expression, although these profiles were substantially different to those in the F2 generation. Likewise adult F1 generation mice showed some abnormalities in social behavior that were sexually dimorphic and milder than those in F2 generation mice. Our results indicate that developmental overexposure to thyroid hormone causes intergenerational epigenetic effects impacting social behavior and the expression of autism-related genes during early brain development. Our results open the possibility that altered thyroid hormone states, by eliciting changes in the epigenetic information of the germ line, contribute to the susceptibility and the missing-but heriTables-etiology of complex neurodevelopmental conditions characterized by social deficits, including autism and schizophrenia.

Chronic Cadmium Exposure Induces Impaired Olfactory Learning and Altered Brain Gene Expression in Honey Bees (Apis mellifera).

The honey bee (Apis mellifera) plays vital ecological roles in the pollination of crops and the maintenance of ecological balance, and adult honey bees may be exposed to exogenous chemicals including heavy metals during their foraging activities. Cadmium (Cd) is regarded as a nonessential toxic metal and is readily accumulated in plants; honey bees can therefore acquire Cd through the collection of contaminated nectar. In the present study, honey bees were chronically exposed to Cd to investigate the effects of sublethal cadmium doses on the olfactory learning and brain gene expression profiles of honey bees. The results showed that Cd-treated bees exhibited significantly impaired olfactory learning performances in comparison with control bees. Moreover, the head weight was significantly lower in Cd-treated bees than in control bees after chronic exposure to Cd. Gene expression profiles between the Cd treatment and the control revealed that 79 genes were significantly differentially expressed. Genes encoding chemoreceptors and olfactory proteins were downregulated, whereas genes involved in response to oxidative stress were upregulated in Cd-treated bees. The results suggest that Cd exposure exerts oxidative stress in the brain of honey bees, and the dysregulated expression of genes encoding chemoreceptors, olfactory proteins, and cytochrome P450 enzymes is probably associated with impaired olfactory learning in honey bees.

TFEB acetylation promotes lysosome biogenesis and ameliorates Alzheimer’s disease–relevant phenotypes in mice

Lysosomes are one of the major centers for regulating cargo degradation and protein quality control. Transcription factor EB (TFEB)-promoted lysosome biogenesis enhances lysosome-mediated degradation and alleviates neurodegenerative diseases, but the mechanisms underlying TFEB modification and activation are still poorly understood. Here, we report essential roles of TFEB acetylation in TFEB nuclear translocation and lysosome biogenesis, which are independent of TFEB dephosphorylation. By screening small molecules, we find that Trichostatin A (TSA), the pan-inhibitor of histone deacetylases (HDACs), promotes nuclear translocation of TFEB. TSA enhances the staining of cells by LysoTracker Red and increases the expression of lysosomal and autophagic genes. We identify four novel acetylated lysine residues in TFEB, which are important for TFEB nuclear translocation and lysosome biogenesis. We show that TFEB acetylation is regulated by HDACs (HDAC5, HDAC6, and HDAC9) and lysine acetyltransferases (KATs), including ELP3, CREBBP, and HAT1. During TSA-induced cytosol-to-nucleus translocation of TFEB, acetylation is independent of TFEB dephosphorylation, since the mTORC1- or GSK3β-related phosphorylation sites on TFEB are still phosphorylated. Administration of TSA to APP/PS1 mice increases the expression of lysosomal and autophagic genes in mouse brains and also improves memory. Accordingly, the β-amyloid plaque burden is decreased. These results show that the acetylation of TFEB, as a novel mechanism of TFEB activation, promotes lysosome biogenesis and alleviates the pathogenesis of Alzheimer's disease. Our results also suggest that HDAC inhibition can promote lysosome biogenesis, and this may be a potential therapeutic approach for the treatment of neurodegenerative diseases and disorders related to HDAC hyperactivation.

Long-day stimulation increases thyroid-stimulating hormone expression and affects gonadal development in chub mackerel

For seasonal breeders, photoperiodic changes are important signals that mark the start of the breeding season. Thyroid-stimulating hormone (TSH) is a glycoprotein hormone that not only promotes the secretion of thyroid hormone but also plays a key role in regulating seasonal reproduction in birds and mammals. However, whether TSH activation has been implicated as a seasonal indicator in fish breeding has not been fully investigated. In this study, we isolated tshb as a starting point to elucidate the effect of photoperiodic changes on the activation of the reproductive axis of chub mackerel. The isolated tshb was classified as tshba, which is widely conserved in vertebrates. The quantitative PCR results showed that tshb was strongly expressed in the pituitary. When female and male chub mackerel with immature gonads were reared for six weeks under different photoperiodic conditions, the gonads developed substantially in the long-day (LD) reared fish compared to those in the short-day reared fish. Real-time PCR results showed that the expression level of tshb in the pituitary gland was significantly elevated in the LD group. Although there was no difference in the gonadotropin-releasing hormone 1 gene expression level in the preoptic area of the brain, follicle-stimulating hormone and luteinizing hormone gene expression levels in the pituitary were also significantly elevated in the LD group. In conclusion, TSH is a potential mediator of seasonal information in the reproductive endocrine axis and may induce gonadal development during the breeding season of chub mackerel.

Functional orderly topography of brain networks associated with gene expression heterogeneity

The human cerebral cortex is vastly expanded relative to nonhuman primates and rodents, leading to a functional orderly topography of brain networks. Here, we show that functional topography may be associated with gene expression heterogeneity. The neocortex exhibits greater heterogeneity in gene expression, with a lower expression of housekeeping genes, a longer mean path length, fewer clusters, and a lower degree of ordering in networks than archicortical and subcortical areas in human, rhesus macaque, and mouse brains. In particular, the cerebellar cortex displays greater heterogeneity in gene expression than cerebellar deep nuclei in the human brain, but not in the mouse brain, corresponding to the emergence of novel functions in the human cerebellar cortex. Moreover, the cortical areas with greater heterogeneity, primarily located in the multimodal association cortex, tend to express genes with higher evolutionary rates and exhibit a higher degree of functional connectivity measured by resting-state fMRI, implying that such a spatial distribution of gene expression may be shaped by evolution and is favourable for the specialization of higher cognitive functions. Together, the cross-species imaging and genetic findings may provide convergent evidence to support the association between the orderly topography of brain function networks and gene expression.

Effects of a novel probiotic mixture on the modulation of brain and intestine Aquaporin-4 gene expression in rats exposed to Cadmium.

Cadmium (Cd) is a toxicant metal that risks human and animal health. Nowadays, the vital role of Aquaporin-4 (AQP-4) in brain and gut cell permeability has gathered too much attention to protecting against heavy metals. Studies have shown that heavy metals can harm the body due to oxidative stress. Probiotics are known for their health-beneficial effects and establish as dietary adjuncts mainly for their antioxidant properties. This study investigated the impact of a novel probiotic combination including Lactobacillus casei IBRC-M10783, Lactobacillus rhamnosus IBRC-M10782, and Lactobacillus helveticus TG-34 on the AQP-4 gene expression in CdCl2-induced Wistar rats. Rats were divided into three groups and received a specific dose of CdCl2 or probiotics. The AQP-4 expression level had estimated by Real-Time PCR in both the intestine and brain. These results showed a significant reduction in AQP-4 gene expression in the probiotic treatment group compared to the CdCl2 control group in the intestine and brain for the first time. Our research showed that consuming a probiotic mixture of L. casei, L. rhamnosus, and L. helveticus can reduce the expression of the aquaporin-4 gene in the brain and intestine of rats exposed to Cadmium, which can be promising in the field of aquaporin-4 regulation.

An Integrative Analysis of Identified Schizophrenia-Associated Brain Cell Types and Gene Expression Changes.

Schizophrenia (SCZ) is a severe mental disorder that may result in hallucinations, delusions, and extremely disordered thinking. How each cell type in the brain contributes to SCZ occurrence is still unclear. Here, we leveraged the human dorsolateral prefrontal cortex bulk RNA-seq data, then used the RNA-seq deconvolution algorithm CIBERSORTx to generate SCZ brain single-cell RNA-seq data for a comprehensive analysis to understand SCZ-associated brain cell types and gene expression changes. Firstly, we observed that the proportions of brain cell types in SCZ differed from normal samples. Among these cell types, astrocyte, pericyte, and PAX6 cells were found to have a higher proportion in SCZ patients (astrocyte: SCZ = 0.163, control = 0.145, P.adj = 4.9 × 10−4, effect size = 0.478; pericyte: SCZ = 0.057, control = 0.066, P.adj = 1.1 × 10−4, effect size = 0.519; PAX6: SCZ = 0.014, control = 0.011, P.adj = 0.014, effect size = 0.377), while the L5/6_IT_CAR3 cells and LAMP5 cells are the exact opposite (L5/6_IT_Car3: SCZ = 0.102, control = 0.108, P.adj = 0.016, effect size = 0.369; LAMP5: SCZ = 0.057, control = 0.066, P.adj = 2.2 × 10−6, effect size = 0.617). Next, we investigated gene expression in cell types and functional pathways in SCZ. We observed chemical synaptic transmission dysregulation in two types of GABAergic neurons (PVALB and LAMP5), and immune reaction involvement in GABAergic neurons (SST) and non-neuronal cell types (endothelial and oligodendrocyte). Furthermore, we observed that some differential expression genes from bulk RNA-seq displayed cell-type-specific abnormalities in the expression of molecules in SCZ. Finally, the cell types with the SCZ-related transcriptomic changes could be considered to belong to the same module since we observed two major similar coordinated transcriptomic changes across these cell types. Together, our results offer novel insights into cellular heterogeneity and the molecular mechanisms underlying SCZ.