Genes Brain and Behavior最新文献

{"title":"Divergent neural nodes are species- and hormone-dependent in the brood parasitic brain","authors":"Fernanda G. Duque,&nbsp;Asma Azam,&nbsp;Amanpreet Kaur,&nbsp;Rachel Pao,&nbsp;Kathleen S. Lynch","doi":"10.1111/gbb.12907","DOIUrl":"10.1111/gbb.12907","url":null,"abstract":"<p>Avian brood parasitism is an evolutionarily derived behavior for which the neurobiological mechanisms are mostly unexplored. We aimed to identify brain regions that have diverged in the brood-parasitic brain using relative transcript abundance of social neuropeptides and receptors. We compared behavioral responses and transcript abundance in three brain regions in the brown-headed cowbird (BHCO), a brood parasite, and a closely related parental species, the red-winged blackbird (RWBL). Females of both species were treated with mesotocin (MT; avian homolog of oxytocin) or saline prior to exposure to nest stimuli. Results reveal that MT promotes approach toward nests with eggs rather than nests with begging nestlings in both species. We also examined relative transcript abundance of the five social neuropeptides and receptors in the brain regions examined: preoptic area (POA), paraventricular nucleus (PVN) and bed nucleus of the stria terminalis (BST). We found that MT-treated cowbirds but not blackbirds exhibited lower transcript abundance for two receptors, corticotropin-releasing factor 2 (CRFR2) and prolactin receptor (PRLR) in BST. Additionally, MT-treated cowbirds had higher PRLR in POA, comparable to those found in blackbirds, regardless of treatment. No other transcripts of interest exhibited significant differences as a result of MT treatment, but we found a significant effect of species in the three regions. Together, these results indicate that POA, PVN, and BST represent neural nodes that have diverged in avian brood parasites and may serve as neural substrates of brood-parasitic behavior.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12907","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commensal bacteria exacerbate seizure-like phenotypes in Drosophila voltage-gated sodium channel mutants","authors":"Patrick Lansdon,&nbsp;Junko Kasuya,&nbsp;Toshihiro Kitamoto","doi":"10.1111/gbb.70000","DOIUrl":"10.1111/gbb.70000","url":null,"abstract":"<p>Mutations in voltage-gated sodium (Na_v) channels, which are essential for generating and propagating action potentials, can lead to serious neurological disorders, such as epilepsy. However, disease-causing Na_v channel mutations do not always result in severe symptoms, suggesting that the disease conditions are significantly affected by other genetic factors and various environmental exposures, collectively known as the “exposome”. Notably, recent research emphasizes the pivotal role of commensal bacteria in neural development and function. Although these bacteria typically benefit the nervous system under normal conditions, their impact during pathological states remains largely unknown. Here, we investigated the influence of commensal microbes on seizure-like phenotypes exhibited by <i>para</i>^<i>Shu</i>—a gain-of-function mutant of the <i>Drosophila</i> Na_v channel gene, <i>paralytic</i>. Remarkably, the elimination of endogenous bacteria considerably ameliorated neurological impairments in <i>para</i>^<i>Shu</i>. Consistently, reintroducing bacteria, specifically from the <i>Lactobacillus</i> or <i>Acetobacter</i> genera, heightened the phenotypic severity in the bacteria-deprived mutants. These findings posit that particular native bacteria contribute to the severity of seizure-like phenotypes in <i>para</i>^<i>Shu</i>. We further uncovered that treating <i>para</i>^<i>Shu</i> with antibiotics boosted Nrf2 signaling in the gut, and that global Nrf2 activation mirrored the effects of removing bacteria from <i>para</i>^<i>Shu</i>. This raises the possibility that the removal of commensal bacteria suppresses the seizure-like manifestations through augmented antioxidant responses. Since bacterial removal during development was critical for suppression of adult <i>para</i>^<i>Shu</i> phenotypes, our research sets the stage for subsequent studies, aiming to elucidate the interplay between commensal bacteria and the developing nervous system in conditions predisposed to the hyperexcitable nervous system.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomics analysis reveals potential regulatory role of nSMase2 (Smpd3) in nervous system development and function of middle-aged mouse brains","authors":"Zhihui Zhu,&nbsp;Timothy S. McClintock,&nbsp;Erhard Bieberich","doi":"10.1111/gbb.12911","DOIUrl":"10.1111/gbb.12911","url":null,"abstract":"<p>Neutral sphingomyelinase-2 (nSMase2), gene name sphingomyelin phosphodiesterase-3 (<i>Smpd3</i>), is a key regulatory enzyme responsible for generating the sphingolipid ceramide. The function of nSMase2 in the brain is still controversial. To better understand the functional roles of nSMase2 in the aging mouse brain, we applied RNA-seq analysis, which identified a total of 1462 differentially abundant mRNAs between <i>+/fro and fro/fro</i>, of which 891 were increased and 571 were decreased in nSMase2-deficient mouse brains. The most strongly enriched GO and KEGG annotation terms among transcripts increased in <i>fro/fro</i> mice included synaptogenesis, synapse development, synaptic signaling, axon development, and axonogenesis. Among decreased transcripts, enriched annotations included ribosome assembly and mitochondrial protein complex functions. KEGG analysis of decreased transcripts also revealed overrepresentation of annotations for Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington disease (HD). Ingenuity Pathway Analysis (IPA) tools predicted lower susceptibility to these neurodegenerative disorders, as well as predictions agreeing with stronger synaptic function, learning, and memory in <i>fro/fro</i> mice. The IPA tools identified signaling proteins, epigenetic regulators, and microRNAs as likely upstream regulators of the broader set of genes encoding the affected transcripts. It also revealed 16 gene networks, each linked to biological processes identified as overrepresented annotations among the affected transcripts by multiple analysis methods. Therefore, the analysis of these RNA-seq data indicates that nSMase2 impacts synaptic function and neural development, and may contribute to the onset and development of neurodegenerative diseases in middle-aged mice.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12911","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The activity-regulated cytoskeleton-associated protein (Arc) functions in a cell type- and sex-specific manner in the adult nucleus accumbens to regulate non-contingent cocaine behaviors","authors":"Daniel J. Wood,&nbsp;Jessica L. Huebschman,&nbsp;Dalia Martinez,&nbsp;Evgeny Tsvetkov,&nbsp;Kirsten Snyder,&nbsp;Raymond Tjhia,&nbsp;Jaswinder Kumar,&nbsp;Brandon W. Hughes,&nbsp;Makoto Taniguchi,&nbsp;Laura N. Smith,&nbsp;Christopher W. Cowan,&nbsp;Rachel D. Penrod","doi":"10.1111/gbb.12910","DOIUrl":"10.1111/gbb.12910","url":null,"abstract":"<p>Repeated cocaine use produces adaptations in brain function that contribute to long-lasting behaviors associated with cocaine use disorder (CUD). In rodents, the activity-regulated cytoskeleton-associated protein (Arc) can regulate glutamatergic synaptic transmission, and cocaine regulates Arc expression and subcellular localization in multiple brain regions, including the nucleus accumbens (NAc)—a brain region linked to CUD-related behavior. We show here that repeated, non-contingent cocaine administration in global <i>Arc</i> KO male mice produced a dramatic hypersensitization of cocaine locomotor responses and drug experience-dependent sensitization of conditioned place preference (CPP). In contrast to the global <i>Arc</i> KO mice, viral-mediated reduction of Arc in the adult male, but not female, NAc (shArc^NAc) reduced both CPP and cocaine-induced locomotor activity, but without altering basal miniature or evoked glutamatergic synaptic transmission. Interestingly, cell type-specific knockdown of Arc in D1 dopamine receptor-expressing NAc neurons reduced cocaine-induced locomotor sensitization, but not cocaine CPP; whereas, Arc knockdown in D2 dopamine receptor-expressing NAc neurons reduced cocaine CPP, but not cocaine-induced locomotion. Taken together, our findings reveal that global, developmental loss of Arc produces hypersensitized cocaine responses; however, these effects cannot be explained by Arc's function in the adult mouse NAc since Arc is required in a cell type- and sex-specific manner to support cocaine-context associations and locomotor responses.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12910","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association study of delay discounting in Heterogeneous Stock rats","authors":"Montana Kay Lara,&nbsp;Apurva S. Chitre,&nbsp;Denghui Chen,&nbsp;Benjamin B. Johnson,&nbsp;Khai-Minh Nguyen,&nbsp;Katarina A. Cohen,&nbsp;Sakina A. Muckadam,&nbsp;Bonnie Lin,&nbsp;Shae Ziegler,&nbsp;Angela Beeson,&nbsp;Thiago M. Sanches,&nbsp;Leah C. Solberg Woods,&nbsp;Oksana Polesskaya,&nbsp;Abraham A. Palmer,&nbsp;Suzanne H. Mitchell","doi":"10.1111/gbb.12909","DOIUrl":"10.1111/gbb.12909","url":null,"abstract":"<p>Delay discounting refers to the behavioral tendency to devalue rewards as a function of their delay in receipt. Heightened delay discounting has been associated with substance use disorders and multiple co-occurring psychopathologies. Human and animal genetic studies have established that delay discounting is heritable, but only a few associated genes have been identified. We aimed to identify novel genetic loci associated with delay discounting through a genome-wide association study (GWAS) using Heterogeneous Stock (HS) rats, a genetically diverse outbred population derived from eight inbred founder strains. We assessed delay discounting in 650 male and female HS rats using an adjusting amount procedure in which rats chose between smaller immediate sucrose rewards or a larger reward at various delays. Preference switch points were calculated and both exponential and hyperbolic functions were fitted to these indifference points. Area under the curve (AUC) and the discounting parameter <i>k</i> of both functions were used as delay discounting measures. GWAS for AUC, exponential <i>k</i>, and one indifference point identified significant loci on chromosomes 20 and 14. The gene <i>Slc35f1</i>, which encodes a member of the solute carrier family, was the sole gene within the chromosome 20 locus. That locus also contained an eQTL for <i>Slc35f1</i>, suggesting that heritable differences in the expression might be responsible for the association with behavior. <i>Adgrl3</i>, which encodes a latrophilin subfamily G-protein coupled receptor, was the sole gene within the chromosome 14 locus. These findings implicate novel genes in delay discounting and highlight the need for further exploration.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-sequencing reveals a shared neurotranscriptomic profile in the medial preoptic area of highly social songbirds and rats","authors":"Brandon J. Polzin,&nbsp;Changjiu Zhao,&nbsp;Sharon A. Stevenson,&nbsp;Stephen C. Gammie,&nbsp;Lauren V. Riters","doi":"10.1111/gbb.12908","DOIUrl":"10.1111/gbb.12908","url":null,"abstract":"<p>Rough-and-tumble play in juvenile rats and song in flocks of adult songbirds outside a breeding context (gregarious song) are two distinct forms of non-sexual social behavior. Both are believed to play roles in the development of sociomotor skills needed for later life-history events, including reproduction, providing opportunities for low-stakes practice. Additionally, both behaviors are thought to be intrinsically rewarded and are associated with a positive affective state. Given the functional similarities of these behaviors, this study used RNA-sequencing to identify commonalities in their underlying neurochemical systems within the medial preoptic area. This brain region is implicated in multiple social behaviors, including song and play, and is highly conserved across vertebrates. DESeq2 and rank–rank hypergeometric overlap analyses identified a shared neurotranscriptomic profile in adult European starlings singing high rates of gregarious song and juvenile rats playing at high rates. Transcript levels for several glutamatergic receptor genes, such as GRIN1, GRIN2A, and GRIA1, were consistently upregulated in highly gregarious (i.e., playful/high singing) animals. This study is the first to directly investigate shared neuromodulators of positive, non-sexual social behaviors across songbirds and mammals. It provides insight into a conserved brain region that may regulate similar behaviors across vertebrates.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-wiring of the bonded brain: Gene expression among pair bonded female prairie voles changes as they transition to motherhood","authors":"Santiago A. Forero,&nbsp;Sydney Liu,&nbsp;Netra Shetty,&nbsp;Alexander G. Ophir","doi":"10.1111/gbb.12906","DOIUrl":"10.1111/gbb.12906","url":null,"abstract":"<p>Motherhood is a costly life-history transition accompanied by behavioral and neural plasticity necessary for offspring care. Motherhood in the monogamous prairie vole is associated with decreased pair bond strength, suggesting a trade-off between parental investment and pair bond maintenance. Neural mechanisms governing pair bonds and maternal bonds overlap, creating possible competition between the two. We measured mRNA expression of genes encoding receptors for oxytocin (<i>oxtr</i>), dopamine (<i>d1r</i> and <i>d2r</i>), mu-opioids (<i>oprm1a</i>), and kappa-opioids (<i>oprk1a</i>) within three brain areas processing salience of sociosensory cues (anterior cingulate cortex; ACC), pair bonding (nucleus accumbens; NAc), and maternal care (medial preoptic area; MPOA). We compared gene expression differences between pair bonded prairie voles that were never pregnant, pregnant (~day 16 of pregnancy), and recent mothers (day 3 of lactation). We found greater gene expression in the NAc (<i>oxtr</i>, <i>d2r</i>, <i>oprm1a</i>, and <i>oprk1a</i>) and MPOA (<i>oxtr</i>, <i>d1r</i>, <i>d2r</i>, <i>oprm1a</i>, and <i>oprk1a</i>) following the transition to motherhood. Expression for all five genes in the ACC was greatest for females that had been bonded for longer. Gene expression within each region was highly correlated, indicating that oxytocin, dopamine, and opioids comprise a complimentary gene network for social signaling. ACC-NAc gene expression correlations indicated that being a mother (<i>oxtr</i> and <i>d1r</i>) or maintaining long-term pair bonds (<i>oprm1a</i>) relies on the coordination of different signaling systems within the same circuit. Our study suggests the maternal brain undergoes changes that prepare females to face the trade-off associated with increased emotional investment in offspring, while also maintaining a pair bond.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12906","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Learning, memory and blood–brain barrier pathology in Duchenne muscular dystrophy mice lacking Dp427, or Dp427 and Dp140","authors":"Minou Verhaeg,&nbsp;Kevin Adamzek,&nbsp;Davy van de Vijver,&nbsp;Kayleigh Putker,&nbsp;Sarah Engelbeen,&nbsp;Daphne Wijnbergen,&nbsp;Maurice Overzier,&nbsp;Ernst Suidgeest,&nbsp;Louise van der Weerd,&nbsp;Annemieke Aartsma-Rus,&nbsp;Maaike van Putten","doi":"10.1111/gbb.12895","DOIUrl":"https://doi.org/10.1111/gbb.12895","url":null,"abstract":"<p>Duchenne muscular dystrophy is a severe neuromuscular disorder that is caused by mutations in the <i>DMD</i> gene, resulting in a disruption of dystrophin production. Next to dystrophin expression in the muscle, different isoforms of the protein are also expressed in the brain and lack of these isoforms leads to cognitive and behavioral deficits in patients. It remains unclear how the loss of the shorter dystrophin isoform Dp140 affects these processes. Using a variety of behavioral tests, we found that <i>mdx</i> and <i>mdx</i>^<i>4cv</i> mice (which lack Dp427 or Dp427 + Dp140, respectively) exhibit similar deficits in working memory, movement patterns and blood–brain barrier integrity. Neither model showed deficits in spatial learning and memory, learning flexibility, anxiety or spontaneous behavior, nor did we observe differences in aquaporin 4 and glial fibrillary acidic protein. These results indicate that in contrast to Dp427, Dp140 does not play a crucial role in processes of learning, memory and spontaneous behavior.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12895","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141251396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavioral transcriptomic effects of triploidy and probiotic therapy (Bifidobacterium, Lactobacillus, and Lactococcus mixture) on juvenile Chinook salmon (Oncorhynchus tshawytscha)","authors":"Chelsea E. Frank,&nbsp;Javad Sadeghi,&nbsp;Daniel D. Heath,&nbsp;Christina A. D. Semeniuk","doi":"10.1111/gbb.12898","DOIUrl":"10.1111/gbb.12898","url":null,"abstract":"<p>Aquaculturists use polyploid fish to maximize production albeit with some unintended consequences including compromised behaviors and physiological function. Given benefits of probiotic therapies (e.g., improved immune response, growth, and metabolism), we explored probiotic supplementation (mixture of <i>Bifidobacterium</i>, <i>Lactobacillus</i>, and <i>Lactococcus</i>), to overcome drawbacks. We first examined fish gut bacterial community composition using 16S metabarcoding (via principal coordinate analyses and PERMANOVA) and determined probiotics significantly impacted gut bacteria composition (<i>p</i> = 0.001). Secondly, we examined how a genomic disruptor (triploidy) and diet supplements (probiotics) impact gene transcription and behavioral profiles of hatchery-reared Chinook salmon (<i>Oncorhynchus tshawytscha</i>). Juveniles from four treatment groups (diploid-regular feed, diploid-probiotic feed, triploid-regular feed, and triploid-probiotic feed; <i>n</i> = 360) underwent behavioral assays to test activity, exploration, neophobia, predator evasion, aggression/sociality, behavioral sensitivity, and flexibility. In these fish, transcriptional profiles for genes associated with neural functions (neurogenesis/synaptic plasticity) and biomarkers for stress response and development (growth/appetite) were (i) examined across treatments and (ii) used to describe behavioral phenotypes via principal component analyses and general linear mixed models. Triploids exhibited a more active behavioral profile (<i>p</i> = 0.002), and those on a regular diet had greater Neuropeptide Y transcription (<i>p</i> = 0.02). A growth gene (early growth response protein 1, <i>p</i> = 0.02) and long-term neural development genes (neurogenic differentiation factor, <i>p</i> = 0.003 and synaptysomal-associated protein 25-a, <i>p</i> = 0.005) impacted activity and reactionary profiles, respectively. Overall, our probiotic treatment did not compensate for triploidy. Our research highlights novel applications of behavioral transcriptomics for identifying candidate genes and dynamic, mechanistic associations with complex behavioral repertoires.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12898","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human-specific insights into candidate genes and boosted discoveries of novel loci illuminate roles of neuroglia in reading disorders","authors":"Wen-Hua Wei,&nbsp;Shaowei Ma,&nbsp;Bo Fu,&nbsp;Ranran Song,&nbsp;Hui Guo","doi":"10.1111/gbb.12899","DOIUrl":"10.1111/gbb.12899","url":null,"abstract":"<p>Reading disorders (RD) are human-specific neuropsychological conditions associated with decoding printed words and/or reading comprehension. So far only a handful of candidate genes segregated in families and 42 loci from genome-wide association study (GWAS) have been identified that jointly provided little clues of pathophysiology. Leveraging human-specific genomic information, we critically assessed the RD candidates for the first time and found substantial human-specific features within. The GWAS candidates (i.e., population signals) were distinct from the familial counterparts and were more likely pleiotropic in neuropsychiatric traits and to harbor human-specific regulatory elements (HSREs). Candidate genes associated with human cortical morphology indeed showed human-specific expression in adult brain cortices, particularly in neuroglia likely regulated by HSREs. Expression levels of candidate genes across human brain developmental stages showed a clear pattern of uplifted expression in early brain development crucial to RD development. Following the new insights and loci pleiotropic in cognitive traits, we identified four novel genes from the GWAS sub-significant associations (i.e., <i>FOXO3</i>, <i>MAPT</i>, <i>KMT2E</i> and <i>HTT</i>) and the Semaphorin gene family with functional priors (i.e., <i>SEMA3A</i>, <i>SEMA3E</i> and <i>SEMA5B</i>). These novel genes were related to neuronal plasticity and disorders, mostly conserved the pattern of uplifted expression in early brain development and had evident expression in cortical neuroglial cells. Our findings jointly illuminated the association of RD with neuroglia regulation—an emerging hotspot in studying neurodevelopmental disorders, and highlighted the need of improving RD phenotyping to avoid jeopardizing future genetic studies of RD.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"23 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12899","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}