Developmental Neuroscience最新文献

{"title":"Obsessive Compulsive Disorder associated with Autoimmunity in Youth: Clinical Course before and after Rituximab+/- Adjunctive Immunomodulation.","authors":"Jennifer Frankovich, Denise Calaprice, Meiqian Ma, Olivia Knight, Kate Miles, Cindy Manko, Joseph D Hernandez, Jesse Sandberg, Bahare Farhadian, Yuhuan Xie, Melissa Silverman, Juliette Madan, Vibeke Strand, Kiki Chang, Margo Thienemann","doi":"10.1159/000544993","DOIUrl":"https://doi.org/10.1159/000544993","url":null,"abstract":"<p><strong>Background: </strong>Multiple lines of evidence suggest that some cases of OCD are underlain by autoimmune and/or inflammatory processes that act on the brain to create neuropsychiatric symptomatology. However, studies of immunomodulatory treatments for such cases are sparse. Here we present consecutive cases of presumed-neuroimmune OCD in youth that have been treated with rituximab +/- adjunctive immunomodulatory treatments.</p><p><strong>Methods: </strong>Of the 458 cases evaluated by our clinic between September 15, 2012 and January 6, 2023, 23 patients were treated with rituximab +/- adjunctive immunomodulation orchestrated by our team (based on evidence of autoimmunity) and were followed routinely by the outpatient clinic team. Patients who presented for a second opinion and were not diagnosed, treated, and/or followed by our outpatient clinic (n=5) or did not have OCD (n=1) are not included. We present the immunological and psychiatric profiles (prior to treatment), selection criteria for use of rituximab, rituximab treatment protocol, recovery status, and reasons for discontinuation (if applicable). Data was obtained from chart review of clinical records. Determination of recovery status was confirmed by the clinical team caring for the patients; patients were classified as: did not recover, partial recovery (PR), or full recovery (FR). Since multiple treatments (psychotherapy, psychiatric medication, and immunomodulation) together contributed to recovery, the team additionally assessed attribution of response to rituximab and details are documented.</p><p><strong>Results: </strong>Patients were between ages of 4 and 20 at initiation of rituximab treatment. All suffered from severe, debilitating neuropsychiatric symptoms prior to rituximab initiation in the context of evidence for systemic autoimmunity. Approximately 70% had an unequivocal recovery following treatment with rituximab (+/- induction and adjunctive immunomodulation) which in most cases allowed the patients to achieve normal levels of function and cease psychotropic medications. Interpretation of attribution in many cases is complicated by the use of induction and adjunct immunomodulation. Most patients experienced transient increases in symptoms before improving; 11 experienced mild self-limited infusion-related reactions, and 14 experienced hypogammaglobulinemia. No patient had an organ or life-threatening reaction or infection following rituximab. One patient developed recurrent sinusitis following rituximab and thus rituximab was stopped despite neuropsychiatric improvements, then rituximab was restarted later due to recrudescence of psychiatric symptoms; the approval to use rituximab with IVIG permitted its use. Patients who received adjunctive immunomodulation (IVIG, methotrexate, leflunomide, etc.) had a higher likelihood of achieving recovery (FR or PR) after rituximab (Fisher's Exact Test, one-sided, p<0.0001).</p><p><strong>Discussion and conclusions: </st","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-26"},"PeriodicalIF":2.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Androgen Aggravates Chorioamnionitis-Induced White Matter Brain Injury and Neurobehavioral Impairments in Males.","authors":"Seline Vancolen, Mathilde Chevin, Marie-Julie Allard, Nour Bouzidi, Bernard Robaire, Guillaume Sébire","doi":"10.1159/000545074","DOIUrl":"10.1159/000545074","url":null,"abstract":"<p><strong>Introduction: </strong>Group B Streptococcus (GBS) colonization leads to placental infection and inflammation, known as chorioamnionitis (CA). Fetal exposure to CA is linked to elevated risks of neurobehavioral impairments in offspring, including autism spectrum disorder, which is more prominent in males than females. In our preclinical model of GBS-induced CA, males exhibited heightened placental inflammation compared to females, correlating with more severe subsequent neurobehavioral impairments. We hypothesize that androgens upregulate the placental immune response in male fetuses, potentially contributing to GBS-induced autistic-like traits in male offspring. Our previous findings demonstrated that there were reduced pro-inflammatory cytokines and polymorphonuclear cell infiltration in flutamide (androgen receptor antagonist) plus GBS-infected compared to vehicle plus GBS-infected placenta. In this study, we investigated the effect of end gestational androgen blockade on brain injury patterns and neurobehavioral outcomes in offspring in utero exposed to GBS CA.</p><p><strong>Methods: </strong>Lewis dams received daily injections of vehicle or flutamide from gestational day (G) 18-21, followed by saline or inactivated GBS injections from G19 to 21. Behavioral assessments were conducted from postnatal day (P) 9-40 and brains were dissected on P50.</p><p><strong>Results: </strong>Behavioral assessments revealed impaired social interactions in CA-exposed versus unexposed male rats. These impairments were not observed in flutamide-treated rats. Histological analysis of forebrains at P50 showed lateral forebrain ventricle enlargement and reduced periventricular white matter thickness, namely the corpus callosum and external capsule in offspring exposed to CA contrasting with an improvement in these outcomes observed in flutamide treated rats. Exposure to CA reduced the density of CC-1+ oligodendrocytes in the external capsule whereas flutamide mitigated this reduction in offspring at P50.</p><p><strong>Conclusion: </strong>These findings suggest a significant role for androgens in the skewed sex ratio observed in developmental impairments resulting from perinatal inflammation, underscoring the need for personalized sex-specific neuroprotective therapies.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-11"},"PeriodicalIF":2.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of light exposure duration on severity and long-term neurodevelopment following photothrombotic stroke in a neonate.","authors":"Arya Jithoo, Tayla Penny, Shu Wen Wen, Althea R Suthya, Yen Pham, Amy E Sutherland, Connie H Y Wong, Suzanne L Miller, Courtney A McDonald","doi":"10.1159/000544994","DOIUrl":"https://doi.org/10.1159/000544994","url":null,"abstract":"<p><p>Introduction Perinatal stroke causes lasting neurological deficits and there are currently no effective treatment options. Established animal models of perinatal stroke do not always mimic the clinical presentation of neonatal injury or are technically challenging to perform. The photothrombotic (PT) stroke model is a minimally invasive method that replicates focal ischemic injury. Few studies have applied the PT model in neonatal contexts, and none have examined both short- and long-term effects across varying injury severities. This study aimed to optimise a protocol to create a mild model of perinatal stroke and subsequently characterize injury progression, neuropathological impact, and motor deficits over time. Methods On post-natal day (PND) 10 we used the PT method to induce perinatal stroke in rat pups. Pups were exposed to various light exposure times (10, 20 or 30 minutes) to determine the optimal time needed to produce a mild and reproducible cortical stroke injury. Behavioural assessments were conducted on days 4, 10, 20, and 30 post-injury. Brains were collected for analysis on days 3 and 40 post-injury. Results 3 days post-injury, the 20 and 30-minute group had significant focal lesions and microbleeds were present in each of the PT groups. All PT groups showed significant neuron loss in the penumbra and the thalamus, and microglia activation in multiple brain regions. As 30 minutes of light exposure showed extensive cortical tissue loss (>70%), we excluded the 30-minute group from long-term assessment. 40 days post-injury, the 10 and 20-minute groups demonstrated significant tissue loss and neuronal loss in the penumbra and thalamus, but only the 20-minute group showed neuron loss in the hippocampus. The 10- and 20-minute groups both demonstrated ongoing motor deficits. Conclusion Our results demonstrate that increasing light exposure time in PT stroke results in a more severe stroke phenotype. 30 minutes of light exposure resulted in a severe injury at only 3 days post insult, therefore, was not further investigated. 10 and 20 minutes of light exposure had a similar effect at 3 days, however after 40 days the 20-minute exposure time created a moderate injury phenotype. From this study we propose that 10 minutes of light exposure is optimal to create a mild stroke phenotype and is associated with motor deficits and altered neuropathology. This injury phenotype provides a focal and reproducible injury, while still being mild enough to feasibly test therapeutics.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-30"},"PeriodicalIF":2.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generating Inhibitory Neuron Diversity through Morphogenic Patterning: From in vivo Studies to New in vitro Models.","authors":"Tanya Deutsch Guerrero, Chloé Borowski, Julien Ferent","doi":"10.1159/000545031","DOIUrl":"10.1159/000545031","url":null,"abstract":"<p><strong>Background: </strong>The proper functioning of the central nervous system depends on the cooperation of distinct neuronal subtypes generated during development.</p><p><strong>Summary: </strong>Here, we review new insights provided by recent research and technological advances into the mechanisms underlying the generation of the remarkable diversity of inhibitory GABAergic neurons (INs). INs are generated in the ventral telencephalon or subpallium and migrate long distances to populate multiple brain regions. INs exhibit considerable morphological, molecular, and electrophysiological diversity. This diversity is mediated by intrinsic and extrinsic factors, including secreted molecules (such as sonic hedgehog).</p><p><strong>Key messages: </strong>This review examines the role of extrinsic factors in the establishment of distinct subpallial domains and the subsequent emergence of IN diversity. We begin by summarizing the in vivo morphogenesis of this process and then highlight the new technologies that allow us to revisit the role of morphogens in subpallial development and IN specification.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-9"},"PeriodicalIF":2.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantifying the Timing of Gyral and Sulcal Formation Relative to Growth in the Ferret Cerebral Cortex.","authors":"Kara E Garcia, Christopher Basinski, Christopher D Kroenke","doi":"10.1159/000544824","DOIUrl":"10.1159/000544824","url":null,"abstract":"<p><strong>Introduction: </strong>Mounting evidence indicates that the cerebral cortical folding pattern conveys information relevant to brain function, as well as the developmental trajectory, leading to the observed pattern at maturity. However, relatively little is known about the biomechanics of gyral and sulcal formation. Ferrets are a tractable animal model for studying folding, in which this process occurs over the first 40 days of postnatal life. Recently, high-resolution magnetic resonance brain imaging data have been made available for a template representing 10 ferrets (5 male, 5 female) at 6 equally spaced time points ranging from postnatal days (P)8 to P38.</p><p><strong>Methods: </strong>For each hemisphere, cerebral cortex surface models representing the template brain at each of the six ages were registered to one another using the anatomical multimodal surface matching (aMSM) algorithm. Local cerebral cortical curvature was determined at each surface vertex at each developmental age, and the T2-weighted images were used to determine cortical thickness at each surface vertex. Relative surface area expansion between pairs of time points was also mapped onto each surface vertex. Systematic comparisons were performed between cortical growth and changes in curvature that accompany gyral and sulcal formation. The sequence of changes of these anatomical characteristics was delineated during folding.</p><p><strong>Results: </strong>The cerebral cortex transitions between two patterns of regionally varying cortical thickness. In early stages of gyral and sulcal formation, the cortex is relatively thick in regions destined to exhibit high magnitudes of surface curvature (folding), regardless of whether the region will become part of a gyrus or a sulcus. In the mature brain, a different regional pattern of thickness is achieved in which gyral cortex is thicker than sulcal cortex. Surface area expansion is also observed to relate to folding, as reflected in the regional pattern of surface curvature changes. Over a given developmental interval, changes in surface curvature are positively correlated with subsequent surface area expansion but negatively correlated with previous surface area expansion.</p><p><strong>Conclusions: </strong>These comparisons lay out a sequence of growth and folding events. First, relative thickening of the cortex occurs in regions that will be gyral and sulcal at maturity. These regions undergo increases in curvature, facilitating surface area increases in the folded cortex. During the final phases of fold formation, the rate of thickness increase in gyri outpaces that in sulci.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-15"},"PeriodicalIF":2.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Long-Term Behavioural Effects of Maternal Creatine Supplementation in a Spiny Mouse Model of Birth Asphyxia.","authors":"Nhi T Tran, James Tran, Tamara Yawno, Rod J Snow, David W Walker, Stacey J Ellery","doi":"10.1159/000544756","DOIUrl":"10.1159/000544756","url":null,"abstract":"<p><strong>Introduction: </strong>Birth asphyxia-induced encephalopathy is a major cause of long-term neurological morbidity, including cognitive and motor deficits. A proposed treatment is maternal creatine supplementation for prophylactic neuroprotection. This study examined how maternal creatine supplementation with or without birth asphyxia affected the behaviour of spiny mice offspring.</p><p><strong>Methods: </strong>On day 20 of gestation (mid-gestation; term = 39 days), dams were randomly allocated to either a daily diet containing 5% w/w creatine monohydrate or remained on standard rodent chow. On gestational day 38, dams underwent either control caesarean section where offspring were delivered and recovered immediately, or birth asphyxia whereby the pregnant uterus was excised and placed in a saline bath for 7.5 min, inducing global hypoxia. All offspring were then cross-fostered to a lactating dam. Behavioural assessments were then completed on recovered offspring from neonatal to adolescent/adult ages (postnatal day [PND] 3-41) using the open-field, elevated plus maze, and novel object recognition test.</p><p><strong>Results: </strong>Offspring that underwent birth asphyxia displayed locomotor deficits and increased anxiety-like behaviour at PND 3-7 in the open-field test (p < 0.05) and impaired novel object discrimination at PND 18 (p < 0.05). Antenatal creatine exposure reduced anxiety-like behaviour irrespective of asphyxia in pups at PND 3, indicating an amelioration of the asphyxia-induced anxiety-like behaviour. In adolescence/adulthood, creatine and asphyxia-exposed offspring showed reduced object exploration (p < 0.0001). Antenatal creatine led to sustained reductions in anxiety-like behaviour in the elevated plus maze at adolescence and increased body weight, regardless of birth asphyxia exposure (p < 0.05).</p><p><strong>Conclusion: </strong>Antenatal creatine exposure following maternal dietary creatine supplementation decreased anxiety-like behaviour in spiny mice offspring. This change negated behavioural abnormalities caused by birth asphyxia in the neonatal period, though it may have broader influences on long-term emotional and information processing in offspring which warrants further investigation.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-15"},"PeriodicalIF":2.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GAPDH, β-Actin, and β-Tubulin Display Age-Dependent Protein Expression Changes in the Mouse Cortex during Development.","authors":"Daniella Rodriguez, Michelle Nguyen, Tejas Devata, Deval Patel, Diana Tavares-Ferreira, Lena H Nguyen","doi":"10.1159/000544064","DOIUrl":"10.1159/000544064","url":null,"abstract":"<p><strong>Introduction: </strong>GAPDH, β-actin, and β-tubulin are essential housekeeping proteins commonly used as reference controls for protein expression studies. GAPDH is a key glycolytic enzyme that facilitates the production of cellular energy, while β-actin and β-tubulin are major structural components of the cytoskeleton. Besides their well-established housekeeping functions, emerging studies have demonstrated critical roles for these proteins in brain developmental and pathological processes. However, few studies have examined how the expression patterns of these proteins change throughout mammalian brain development to adulthood. Considering the dynamic structural and functional changes that occur during brain development and the roles of GAPDH, β-actin, and β-tubulin in related biological processes, we investigated the developmental expression levels of these proteins in the mouse cortex at various embryonic and postnatal stages.</p><p><strong>Methods: </strong>Cortical tissue was collected from mice at embryonic days 15 and 17, postnatal days 0, 5, 10, 15, 20, and during adulthood. Protein levels were analyzed using western blotting analysis with total protein normalization.</p><p><strong>Results: </strong>We identified a substantial increase in GAPDH protein levels and a decrease in β-actin and β-tubulin protein levels in the mouse cortex between birth and early adulthood, which occurred during the second week of postnatal life. Analysis of RNA-seq data from the ENCODE Consortium revealed correlated changes at the RNA transcript level.</p><p><strong>Conclusion: </strong>Overall, our study reveals robust age-dependent changes in cortical GAPDH, β-actin, and β-tubulin expression levels during mouse postnatal development and suggests precautions when using these proteins as reference controls in cortical development studies.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-12"},"PeriodicalIF":2.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth Differentiation Factor-15 Knockout Mice Are Protected from Neonatal Hypoxic-Ischemic Injury in a Sex-Dependent Manner.","authors":"Jeremy R Herrmann, Patrick M Kochanek, Vincent A Vagni, Keri A Janesko-Feldman, Jason P Stezoski, Travis C Jackson","doi":"10.1159/000544063","DOIUrl":"10.1159/000544063","url":null,"abstract":"<p><strong>Introduction: </strong>Neuroinflammation plays a critical role in tissue injury and repair after neonatal hypoxic-ischemic (HI) brain injury and varies by sex. Growth differentiation factor-15 (GDF-15) is a cytokine released by macrophages during inflammation and is upregulated after brain ischemia. We examined the impact of GDF-15 knockout (KO) on volume loss and the combined microglia/macrophage response in the Rice-Vannucci model of neonatal HI injury.</p><p><strong>Methods: </strong>Male and female wild-type (WT) Gdf15+/+, heterozygous Gdf15nuGFP-CE/+ (Het), and homozygous Gdf15nuGFP-CE/nuGFP-CE (KO) mice were bred at the University of Pittsburgh. Postnatal day 9-11 mice were randomized to sham procedure or unilateral common carotid artery ligation followed by exposure to 8% O2 for 25 min. Pups were subsequently genotyped and survived for 14 days before sacrifice. Lesion volume and number of ionized calcium-binding adapter molecule 1 (Iba-1)-positive cells were quantified.</p><p><strong>Results: </strong>Injured male KO pups had decreased hemispheric and hippocampal lesion volume versus injured male WT pups. Injured male Het pups demonstrated an intermediate phenotype. In males, the number of Iba-1-positive cells correlated with extent of tissue loss. In females, the extent of volume loss and Iba-1 cell counts post-injury did not vary by genotype.</p><p><strong>Conclusion: </strong>GDF-15 exerts a sex-dependent deleterious effect on lesion volume in a neonatal HI model. Future work should identify how GDF-15 mediates different neuroinflammatory responses between sexes, establish if brain-secreted versus peripherally derived GDF-15 mediates the pro-injury phenotype that was inhibited in male KOs, and test if therapeutic inhibition of GDF-15 signaling is a novel treatment for neonatal HI brain injury.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-10"},"PeriodicalIF":2.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eight Cases of Pediatric Acute-Onset Neuropsychiatric Syndrome with Inflammatory Bowel Disease: Immunologic Intersections.","authors":"Angela W Tang, Paula M Prieto Jimenez, Ian K T Miller, Juliette C Madan, Jaden Nguyen, Meiqian Ma, Melissa Silverman, Bahare Farhadian, Jenny Wilson, Alka Goyal, Cindy Manko, Yinka Davies, Shervin Rabizadeh, Jennifer Frankovich","doi":"10.1159/000543969","DOIUrl":"10.1159/000543969","url":null,"abstract":"<p><strong>Introduction: </strong>Pediatric acute-onset neuropsychiatric syndrome (PANS) is an immune-mediated disease characterized by abrupt onset neurobehavioral changes. Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn's disease (CD), chronic conditions characterized by gastrointestinal inflammation. We describe eight individuals with both PANS and IBD.</p><p><strong>Methods: </strong>All individuals with both IBD and PANS were identified from Stanford Immune Behavioral Health Clinic, Cedars-Sinai Medical Center Pediatric Inflammatory Bowel Disease Program, and Dartmouth Neuroimmune Psychiatric Disorders (NIPD) Clinic. Data were collected by chart review.</p><p><strong>Results: </strong>Eight cases of PANS with IBD were identified. Five were male. The mean age of onset was 9.3 years for PANS and 15.6 years for IBD. PANS preceded development of IBD in 7 of 8 cases by a mean of 8.4 years. Seven patients (88%) had a first-degree relative with an immune-mediated disease, including 5 with psoriasis or psoriatic arthritis. Five patients themselves had arthralgias or arthritis (63%). All 5 cases where PANS preceded IBD treatment sufficiently for analysis were free of major behavioral relapses after IBD was managed.</p><p><strong>Conclusion: </strong>The triad of PANS, joint complaints, and family history of autoimmunity, including psoriasis, may represent a subset of PANS at heightened risk for IBD and additional immune-mediated disorders. For children with this triad, clinicians should have a low threshold to evaluate for gastrointestinal inflammation with biomarkers like hemoglobin, CRP, fecal calprotectin, and diagnostic endoscopy when indicated. PANS symptoms may improve with effective treatment of IBD. The high prevalence of joint complaints in our cohort and psoriasis in first-degree family members suggests this subset of PANS may share immune mechanisms with psoriasis and arthritis. Treatment strategies used in IBD and arthritis should be studied for potential application in PANS.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-16"},"PeriodicalIF":2.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transferring Mouse Emx1 and Emx2 Lentiviruses into the Chicken Embryonic Brain and Their Implication to the Organization and Evolution of the Amniote Pallium.","authors":"Rui Zhao, Yuanyuan Gao, Chao Xi, Ping Liu, Shiying Lin, Shan Lu, Jin Liu, Jie Bing, Xinwen Zhang, Shaoju Zeng","doi":"10.1159/000543601","DOIUrl":"10.1159/000543601","url":null,"abstract":"<p><strong>Introduction: </strong>Homeobox genes are highly conserved and play critical roles in brain development. Recently, we have found that mammals have an additional fragment of approximately 20 amino acids in Emx1 and a poly-(AL)6-7 in Emx2, compared to other amniotes. It has been shown that Emx1 and Emx2 have synergistic actions in the brain development. These reports raise an interesting issue whether the differences of Emx1 and Emx2 between mammals and non-mammals are concerned with the organization and evolution of amniote pallium.</p><p><strong>Methods: </strong>Lentiviruses expressing mouse Emx1 and Emx2 (mEmx1/2) with additional fragments were injected into the ventricle of the chick telencephalon at embryonic day 3 to study the effects of mEmx1/2 on the development of chick pallium, whereas injections of lentiviruses containing chick Emx1 and Emx2 (cEmx1/2), no targeted gene insert or saline were as controls. The expressions of reelin, vimentin, GABA and MAP2, neurogenesis patterns for calbindin (CB) and parvalbumin (PV) neurons and the sizes of anterior commissure (AC) were then studied by immuohistochemical staining, and open-field tests were performed to assess locomotor activities and curious or exploratory behaviors of the chicks.</p><p><strong>Results: </strong>Following the injections of lentiviruses expressing mEmx1/2, the expressions of reelin, vimentin, GABA, and MAP2 increased in most parts of Wulst (W) and mesopallium (M), but not most of nidopallium (N). Neurogenesis patterns for CB and PV neurons changed toward mammalian inside-out one, and the sizes of AC staining for neurofilament were significantly larger. In addition, post-hatchling chicks showed higher rates of passive avoidance after training, but no significant differences in the total distance traveled and the percentage of time spent in the central rectangle, compared to those in the control groups.</p><p><strong>Conclusion: </strong>The present study indicated that mEmx1/2 had effects on the development of chick pallium, suggesting that they are probably involved in the organization and evolution of amniote pallium.</p>","PeriodicalId":50585,"journal":{"name":"Developmental Neuroscience","volume":" ","pages":"1-18"},"PeriodicalIF":2.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}