Physiological genomics最新文献

{"title":"Gut microbial composition and diversity varies by <i>CREBRF</i> genotype among Samoan infants.","authors":"Sakurako Oyama, Kendall J Arslanian, Maria Luisa Savo Sardaro, Rachel L Duckham, Erin E Kershaw, Ashlee N Wood, Ulai T Fidow, Take Naseri, Muagututia S Reupena, Katherine R Amato, Nicola L Hawley","doi":"10.1152/physiolgenomics.00014.2024","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00014.2024","url":null,"abstract":"<p><p><b>Introduction:</b> Over 40% of Samoans have at least one copy of the minor A allele at rs373863828 in CREB3 regulatory factor (<i>CREBRF</i>), which is associated with increased BMI but decreased odds of type 2 diabetes mellitus. The mechanisms underlying this paradoxical effect remain unknown. We hypothesized that gut microbiota may play a role and examined associations between <i>CREBRF</i> genotype and gut microbial diversity and composition among Samoan infants. <b>Methods:</b> Fecal samples were collected from Samoan infants aged 0 (n=23), 4 (n=20), and 21 (n=27) months. Microbiota community structure was analyzed using 16S rRNA bacterial gene sequencing. <b>Results:</b> Both cross-sectional and longitudinal analyses revealed no associations between <i>CREBRF</i> genotype and overall microbiome composition or diversity at 0 or 4 months. Cross-sectional analysis at 21 months revealed a significant association between genotype and unweighted UniFrac distances (F1,24=1.855, R2=0.072, p=0.015). Longitudinal differential abundance analysis also revealed several differentially abundant taxa at 21 months. Notably, the AG genotype was associated with lower relative abundance of <i>Escherichia Shigella</i> (β=-6.741, SE=2.243, p=.004, q=.042). <b>Discussion:</b> Significant genotype differences in gut microbiome composition and diversity at 21 months suggest that gut microbiota may be involved in relationships between <i>CREBRF</i> genotype and metabolic health. No genotype differences were observed at 0 or 4 months, suggesting that environmental and/or maternal variables have greater influence on the gut microbiome in early infancy and genotype effects emerge later. Further research should examine whether genotype differences in gut microbiota are associated with functional differences in metabolic or immune signaling pathways or energy extraction.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Better Way to Assess Developmental Competence of Mammalian Early Embryos?","authors":"Andrew J Watson","doi":"10.1152/physiolgenomics.00055.2025","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00055.2025","url":null,"abstract":"","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional Dynamics of Sleep Deprivation and Subsequent Recovery Sleep in the Male Mouse Cortex.","authors":"Alexander Popescu, Caitlin Ottaway, Kaitlyn Ford, Elizabeth Medina, Taylor Wintler, Ashley Ingiosi, Stephanie C Hicks, Kristan Singletary, Lucia Peixoto","doi":"10.1152/physiolgenomics.00128.2024","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00128.2024","url":null,"abstract":"<p><p>Sleep is an essential, tightly regulated biological function. Sleep is also a homeostatic process, with the need to sleep increasing as a function of being awake. Acute sleep deprivation (SD) increases sleep need, and subsequent recovery sleep (RS) discharges it. SD is known to alter brain gene expression in rodents, but it remains unclear which changes are linked to sleep homeostasis. To investigate this question, we analyzed RNA-seq data from adult male mice subjected to 3 and 5-6 hours of SD and 2 and 6 hours of subsequent RS. We hypothesized molecular changes associated with sleep homeostasis mirror sleep pressure dynamics as defined by brain electrical activity, peaking at 5-6 hours of SD and no longer differentially expressed after 2 hours of RS. We report 5-6 hours of SD produces the largest effect on gene expression and the majority of DEGs normalize after 2 hours of RS. These genes are involved in cellular redox homeostasis, DNA damage/repair and chromatin regulation, and may underlie the molecular basis of sleep homeostasis. Genes associated with cellular stress do not normalize within 6 hours of RS and may underlie non-sleep specific effects of SD. Additionally, RS affects gene expression related to energy metabolism and Wnt-signaling, potentially contributing to its restorative effects. Finally, our study also points to the regulation of expression of a subset of circadian transcription factors as a function of sleep need. Overall, our results offer novel insights into the molecular mechanisms underlying sleep homeostasis and the broader effects of SD.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent multiomic acute exercise responses reveal the impact of sex as a biological variable.","authors":"Kaleen M Lavin, Samia M O'Bryan, Khyatiben V Pathak, Krystine Garcia-Mansfield, Zachary A Graham, Jeremy S McAdam, Devin J Drummer, Margaret B Bell, Christian J Kelley, Manoel E Lixandrão, Brandon Peoples, Regina S Seay, Anakaren R Torres, Rebecca Reiman, Eric Alsop, Elizabeth Hutchins, Anna Bonfitto, Jerry Antone, Joanna Palade, Kendall Van Keuren-Jensen, Matthew J Huentelman, Patrick Pirrotte, Timothy Broderick, Marcas M Bamman","doi":"10.1152/physiolgenomics.00055.2024","DOIUrl":"10.1152/physiolgenomics.00055.2024","url":null,"abstract":"<p><p>The majority of exercise physiology research has been conducted in males, resulting in a skewed biological representation of how exercise impacts the physiological system. Extrapolating male-centric physiological findings to females is not universally appropriate and may even be detrimental. Thus, addressing this imbalance and taking into consideration sex as a biological variable is mandatory for optimization of precision exercise interventions and/or regimens. Our present analysis focused on establishing multiomic profiles in young, exercise-naïve males (<i>n</i> = 23) and females (<i>n</i> = 17) at rest and following acute exercise. Sex differences were characterized at baseline and following exercise using skeletal muscle and extracellular vesicle transcriptomics, whole blood methylomics, and serum metabolomics. Sex-by-time analysis of the acute exercise response revealed notable overlap, and divergent molecular responses between males and females. An exploratory comparison of two combined exercise regimens [high-intensity tactical training (HITT) and traditional (TRAD)] was then performed using singular value decomposition, revealing latent data structures that suggest a complex dose-by-sex interaction response to exercise. These findings lay the groundwork for an understanding of key differences in responses to acute exercise exposure between sexes. This may be leveraged in designing optimal training strategies, understanding common and divergent molecular interplay guiding exercise responses, and elucidating the role of sex hormones and/or other sex-specific attributes in responses to acute and chronic exercise.<b>NEW & NOTEWORTHY</b> This study examined methylomics, transcriptomics, and metabolomics in circulation and/or skeletal muscle of young, healthy, exercise-naïve males and females before and after exposure to either traditional combined exercise (TRAD) and high-intensity tactical training (HITT). Across 40 young adults, we found an overlapping yet considerably sex-divergent response in the molecular mechanisms activated by exercise. These findings may provide insight into optimal training strategies for adaptation when considering sex as a biological variable.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"321-342"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence of a novel gene locus <i>ARHGAP44</i> for longitudinal change in hemoglobin A1c levels among subjects without diabetes from the Long Life Family Study.","authors":"Siyu Wang, Petra Lenzini, Bharat Thyagarajan, Joseph H Lee, Badri N Vardarajan, Anatoli Yashin, Iva Miljkovic, E Warwick Daw, Shiow J Lin, Gary J Patti, Michael R Brent, Joseph M Zmuda, Thomas T Perls, Kaare Christensen, Michael A Province, Ping An","doi":"10.1152/physiolgenomics.00137.2024","DOIUrl":"10.1152/physiolgenomics.00137.2024","url":null,"abstract":"<p><p>Glycated hemoglobin A1c (HbA1c) indicates average glucose levels over 3 mo and is associated with insulin resistance and type 2 diabetes (T2D). Longitudinal change in circulating HbA1c (ΔHbA1c) is also associated with aging processes, cognitive performance, and mortality. We analyzed ΔHbA1c in 1,886 nondiabetic Europeans from the Long Life Family Study (LLFS) to uncover gene loci influencing ΔHbA1c. Using growth curve modeling adjusted for multiple covariates, we derived ΔHbA1c and conducted linkage-guided sequence analysis. Our genome-wide linkage scan identified a significant locus on <i>17p12</i>. In-depth analysis revealed a gene locus <i>ARHGAP44</i> (rs56340929, explaining 27% of the linkage peak) that was significantly associated with ΔHbA1c. Interestingly, RNA transcription of <i>ARHGAP44</i> was also significantly associated with ΔHbA1c in the LLFS, and this discovery was replicable on the gene locus level in the Framingham Offspring Study (FOS). Taking together, we successfully identified a novel gene locus <i>ARHGAP44</i> for ΔHbA1c in family members without T2D. Further follow-up studies using longitudinal omics data in large independent cohorts are warranted.<b>NEW & NOTEWORTHY</b> HbA1c is clinically used in T2D diagnosis and monitoring. Its longitudinal change (ΔHbA1c) is associated with T2D-related aging processes and mortality. Targeted association tests under significant linkage peaks in extended families permit identification of unique gene loci. We uncovered a novel gene locus <i>ARHGAP44</i> for ΔHbA1c with gene-level validations from the FOS and RNAseq data in the LLFS. The finding provides genetically informed biological insight into mechanistic inference of glycemia/HbA1c homeostasis and potential T2D pathophysiology.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"293-298"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel effects of reverse transcriptase inhibitor supplementation in skeletal muscle of old mice.","authors":"Shelby C Osburn, Meghan E Smith, Devin Wahl, Thomas J LaRocca","doi":"10.1152/physiolgenomics.00115.2024","DOIUrl":"10.1152/physiolgenomics.00115.2024","url":null,"abstract":"<p><p>Aging is the primary risk factor for the development of many chronic diseases, including dementias, cardiovascular disease, and diabetes. There is significant interest in identifying novel \"geroprotective\" agents, including by repurposing existing drugs, but such treatments may affect organ systems differently. One current example is the nucleoside reverse transcriptase inhibitor 3TC, which has been increasingly studied as a potential gerotherapeutic. Recent data suggest that 3TC may reduce inflammation and improve cognitive function in older mice; however, the effects of 3TC on other tissues in aged animals are less well characterized. Here, we use transcriptomics (RNA-seq) and targeted metabolomics to investigate the influence of 3TC supplementation on skeletal muscle in older mice. We show that 3TC <i>1</i>) does not overtly affect muscle mass or functional/health markers, <i>2</i>) largely reverses age-related changes in gene expression and metabolite signatures, and <i>3</i>) is potentially beneficial for mitochondrial function in old animals via increases in antioxidant enzymes and decreases in mitochondrial reactive oxygen species. Collectively, our results suggest that, in addition to its protective effects in other tissues, 3TC supplementation does not have adverse effects in aged muscle and may even protect muscle/mitochondrial health in this context.<b>NEW & NOTEWORTHY</b> Recent studies suggest that the nucleoside reverse transcriptase inhibitor 3TC may improve brain health and cognitive function in old mice, but its effects on other aging tissues have not been comprehensively studied. This is the first study to use a multiomics approach to investigate the effects of 3TC treatment on skeletal muscle of old mice. The results suggest that 3TC reverses age-related transcriptomic and metabolite signatures and is potentially beneficial for mitochondrial function in aged muscle.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"308-320"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From castaways to discoveries: unveiling treasures in skin RNAseq using a novel multidimensional data processing workflow including infection-host dynamics.","authors":"Disha Bhargava, Alec Labadie, Rebecca L Hanson-Rios-Stutz, Austin Goodyke, Ella M Moses, Akansha S Das, Sophie Vanderweele, Janelle V Lemon, Taylor W Cook, David Pearson, Joseph M Redinger, Adam J Caulfield, Rosemary Olivero, Kate Foster, Kurt Ashack, Surender Rajasekaran, Caleb P Bupp, Timothy J Triche, Connie M Krawczyk, Dave Chesla, Matthew D Sims, Nicholas L Hartog, Jeremy W Prokop","doi":"10.1152/physiolgenomics.00093.2024","DOIUrl":"10.1152/physiolgenomics.00093.2024","url":null,"abstract":"<p><p>Defining physiology and methods to measure biological mechanisms is essential. Extensive datasets such as RNA sequencing are used with little analysis of the knowledge gained from the various methodologies. Within this work, we have processed publicly available NCBI RNAseq datasets using a combination of bioinformatics tools for the largest physiological organ, the skin. In many datasets, we identify the quality of the sample, human transcript mapping, the sex of each sample, foreign RNA from bacteria/viruses/protists, and the presence of B/T-cell immune repertoire. Processing 8,274 samples from 132 different experiments for skin samples identifies common flora of skin with elevation of protists (such as <i>Leishmania</i>), bacteria (<i>Staphylococcus</i>, <i>Cutibacterium acnes</i>), and viruses [Human alphaherpesvirus (HSV), Human papillomavirus (HPV)] that may be involved in physiological differences. We observed samples with the Heilongjiang tick virus, human T-cell leukemia virus type I, and equine infectious anemia virus that likely play pathological roles in physiology. Integrating the various biomarkers identified five ideal datasets for skin pathologies that elucidated a novel correlation between the normal skin flora bacterium <i>Bacillus megaterium</i> with major histocompatibility complex (MHC) regulation and the immune repertoire clonal expansion, particularly in patients with hidradenitis suppurativa. Finally, we show that in multiple independent experiments, biological sex is associated with multiple sex chromosome gene differences, highlighting the importance of future work in studying sex differences in skin. Data integrations and multidimensional data mapping are critical for physiological omics advancements, and this work highlights the exciting ability to apply these tools to skin physiology.<b>NEW & NOTEWORTHY</b> Complex bioinformatics mapping to skin RNA sequencing datasets can simultaneously map biological sex, skin-specific genes, bacteria, viruses, protists, and the acquired immune response. The integration of these datasets elucidated bacterial signatures from common skin flora while identifying novel insights on <i>Bacillus megaterium</i> in the acquired immune response and novel viral signatures for Heilongjiang tick virus and equine infectious anemia virus.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"343-356"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in the bacterial communities along the intestinal tract of juvenile channel (<i>Ictalurus punctatus</i>) and hybrid (<i>I. punctatus</i>× <i>I. furcatus</i>) catfish.","authors":"Caitlin E Older, Penelope M Goodman, J Grant Reifers, Fernando Y Yamamoto","doi":"10.1152/physiolgenomics.00008.2025","DOIUrl":"10.1152/physiolgenomics.00008.2025","url":null,"abstract":"<p><p>Hybrid catfish (<i>Ictalurus punctatus</i> × <i>I. furcatus</i>) is the preferred catfish for US aquaculture due to the heterosis exhibited in many production traits. Improvements in fry production protocols have enabled widespread adoption of these hybrids, with producers using management practices optimized for channel catfish. Research to consider differences, outside of production traits, which may exist between hybrids and their parent species is lacking. Utilizing management practices specifically designed for hybrids may improve production efficiency. The gut microbiome plays critical roles in host development and health and, thus, is relevant to production. In the present study, the microbiota in the anterior, middle, and posterior segments of the intestinal tract were compared between channel and hybrid catfish using high-throughput 16S rRNA gene sequencing. Bacterial community structure was different between channels and hybrids across all intestinal segments (<i>P</i> < 0.05) despite a lack of difference in community diversity. <i>Cetobacterium</i> spp. were found in higher abundances in the middle intestinal segment of hybrids compared with channels (<i>q</i> = 0.02) and found to have a trend of increasing abundance with increasingly distal segments in both channels and hybrids (<i>q</i> < 0.05). <i>Vibrio</i> spp., a low-abundance taxon, was similarly found in higher abundances in the anterior segment of hybrids. These results provide evidence of differences in the gut microbiomes of channels and hybrids and insight into the bacterial communities along the catfish intestinal tract. Additional research will be valuable in understanding why do differences between channel and hybrid catfish exist and how they may contribute to variation in gut microbiome-related production traits.<b>NEW & NOTEWORTHY</b> Hybrid and channel catfish are inhabited by gut bacterial communities of similar overall diversity but of significantly different structure and composition. <i>Cetobacterium</i> spp., a genus previously shown to confer benefits in other hosts, was found in higher abundances in the middle intestinal segment of hybrids and was found to have increasing abundance along the intestinal tract of both channels and hybrids.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"299-307"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged obesity alters males' adipose profile: implications for disease?","authors":"Jessica L Faulkner","doi":"10.1152/physiolgenomics.00191.2024","DOIUrl":"10.1152/physiolgenomics.00191.2024","url":null,"abstract":"","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"254-255"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental pyrethroid exposure disrupts molecular pathways for MAP kinase and circadian rhythms in mouse brain.","authors":"Jennifer H Nguyen, Melissa A Curtis, Ali S Imami, William G Ryan, Khaled Alganem, Kari L Neifer, Nilanjana Saferin, Charlotte N Nawor, Brian P Kistler, Gary W Miller, Rammohan Shukla, Robert E McCullumsmith, James P Burkett","doi":"10.1152/physiolgenomics.00033.2024","DOIUrl":"10.1152/physiolgenomics.00033.2024","url":null,"abstract":"<p><p>Neurodevelopmental disorders (NDDs) are a category of pervasive disorders of the developing nervous system with few or no recognized biomarkers. A significant portion of the risk for NDDs, including attention deficit hyperactivity disorder (ADHD), is contributed by the environment, and exposure to pyrethroid pesticides during pregnancy has been identified as a potential risk factor for NDD in the unborn child. We recently showed that low-dose developmental exposure to the pyrethroid pesticide deltamethrin in mice causes male-biased changes to ADHD- and NDD-relevant behaviors as well as the striatal dopamine system. Here, we used an integrated multiomics approach to determine the broadest possible set of biological changes in the mouse brain caused by developmental pyrethroid exposure (DPE). Using a litter-based, split-sample design, we exposed mouse dams during pregnancy and lactation to deltamethrin (3 mg/kg or vehicle every 3 days) at a concentration well below the EPA-determined benchmark dose used for regulatory guidance. We raised male offspring to adulthood, euthanized them, and pulverized and divided whole brain samples for split-sample transcriptomics, kinomics, and multiomics integration. Transcriptome analysis revealed alterations to multiple canonical clock genes, and kinome analysis revealed changes in the activity of multiple kinases involved in synaptic plasticity, including the mitogen-activated protein (MAP) kinase ERK. Multiomics integration revealed a dysregulated protein-protein interaction network containing primary clusters for MAP kinase cascades, regulation of apoptosis, and synaptic function. These results demonstrate that DPE causes a multimodal biophenotype in the brain relevant to ADHD and identifies new potential mechanisms of action.<b>NEW & NOTEWORTHY</b> Here, we provide the first evidence that low-dose developmental exposure to a pyrethroid pesticide, deltamethrin, results in molecular disruptions in the adult mouse brain in pathways regulating circadian rhythms and neuronal growth (MAP kinase). This same exposure causes a neurodevelopmental disorder (NDD)-relevant behavioral change in adult mice, making these findings relevant to the prevention of NDDs.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"240-253"},"PeriodicalIF":2.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}