Developmental Neurobiology最新文献

{"title":"The Rare Syndrome Aicardi–Goutières 4: A Case Report and Literature Review","authors":"Hilal Aydin,&nbsp;Hilmi Bolat","doi":"10.1002/dneu.22965","DOIUrl":"https://doi.org/10.1002/dneu.22965","url":null,"abstract":"<p>Aicardi–Goutières syndrome (AGS) is a genetically heterogeneous type of interferonopathy resulting from defects in the processing or sensing of nucleic acids. The AGS phenotype encompasses a broad range of neurological and non-neurological findings. It presents with a congenital or subacute onset, manifesting as microcephaly, spasticity, dystonia, seizures, cortical blindness, and psychomotor retardation in the first year of life. The radiological and laboratory findings of AGS are generally accompanied by intracranial calcification, white matter abnormalities, cerebral atrophy, and cerebrospinal fluid lymphocytic pleocytosis. A case diagnosed as AGS type 4 among patients presenting to the Balikesir University Medical Faculty pediatric neurology clinic, Türkiye, between August 1, 2024, and February 1, 2025, and undergoing genetic testing was included in the study. The patient exhibited a coarse facial appearance, a low ear line, scoliosis, contractures in the upper and lower extremities, hyperactive deep tendon reflexes, an equivocal Babinski response, and upper and lower extremity muscle strength of 3/5. The patient was started on levetiracetam at 20 mg/kg in two doses for epilepsy. Whole exome sequencing revealed a homozygous pathogenic variant in <i>RNASEH2A</i>. Parental genetic analyses for the targeted variant were heterozygous. In conclusion, the diagnosis of AGS relies on clinical characteristics and genetic testing. Basic neurological characteristics include developmental delay, dystonia, microcephaly, brain calcification, and leukodystrophy. Although data concerning genotype-phenotype in AGS type 4 have been reported in the literature, these are still limited.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22965","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Treadmill Exercise and Zinc Supplementation Alleviate Prenatal Stress–Induced Cognitive Deficits and Restore Neurological Biomarkers in Offspring: A Study on Male Rats Aged 30 and 90 Days","authors":"Sina Fatehfar,&nbsp;Parsa Sameei,&nbsp;Naseh Abdollahzade,&nbsp;Leila Chodari,&nbsp;Ehsan Saboory,&nbsp;Shiva Roshan-Milani","doi":"10.1002/dneu.22964","DOIUrl":"https://doi.org/10.1002/dneu.22964","url":null,"abstract":"<div>\u0000 \u0000 <p>The detrimental effects of prenatal stress (PS) on offspring's neurological and behavioral outcomes are well documented. However, strategies to mitigate these effects are underexplored. This study examines whether prenatal zinc supplementation and treadmill exercise can modulate PS-induced cognitive impairments and neurobiological markers in young and adult male rat offspring, leveraging the established neuroprotective potential of both physical activity and zinc. Pregnant rats were divided into five groups: control, stress, stress + exercise, stress + zinc, and stress + exercise + zinc, with all rats except the control group subjected to restraint stress (gestational days 15–19). Pregnant rats in the exercise groups underwent forced exercise, whereas those in the zinc groups received oral zinc sulfate throughout the pregnancy. At postnatal days 30 and 90, the cognitive function of male offspring was evaluated using the Morris water maze (MWM) test, and the hippocampal gene expression levels of caspase-3, brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) were measured using reverse transcription–polymerase chain reaction (RT-PCR). PS impaired cognitive functions, increased caspase-3 expression, and decreased BDNF and GFAP expression levels in adult rats. Prenatal exercise was found to mitigate PS-induced cognitive deficits primarily through enhancing GFAP expression, whereas prenatal zinc improved PS-induced cognitive impairments mainly through reduced caspase-3 and increased BDNF expression. The combined effect of exercise and zinc was not additive on cognitive functions and biomarkers. Physical activity may alleviate PS-induced cognitive deficits by modulating astrocytic factors, whereas zinc may exert its effects by inhibiting apoptosis via a BDNF-dependent pathway. Further targeted research is necessary to confirm these relationships.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793649","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":"Azilsartan Confers Protection Against Kainic Acid–Induced Hippocampal Neuron Damage by Upregulating Sirt3/Sod2 Pathway","authors":"Hui-hui Lv,&nbsp;Mao-ying Xia","doi":"10.1002/dneu.22962","DOIUrl":"https://doi.org/10.1002/dneu.22962","url":null,"abstract":"<div>\u0000 \u0000 <p>Epilepsy refers to a diverse group of neurological pathologies, coupled with a significant worldwide impact. Azilsartan, an angiotensin receptor blocker, is broadly applied as an antihypertensive medication. Considering that the neuroprotective potential of Azilsartan has been newly documented, our work was committed to characterizing the association of Azilsartan with epilepsy and its possible mechanism. First, mice hippocampal neuron (HT-22) cells were exposed to kainic acid (KA) with or without Azilsartan treatment. Cell Counting Kit 8 (CCK8) method assessed the viability of KA-treated HT-22 cells. Flow cytometry assay was employed to detect cellular apoptotic capacity. DCF-DA fluorescent staining, JC-1 probe, and related assay kits were used to estimate mitochondrial oxidative stress. Western blotting examined the expression of Sirtuin 3 (Sirt3), superoxide dismutase 2 (Sod2), and apoptosis-related proteins. Additionally, Sirt3 was silenced to analyze whether the protective effect of Azilsartan on KA-induced damage of HT-22 cell damage was achieved by regulating Sirt3. Results indicated that KA intervention concentration-dependently triggered the viability loss, apoptosis, and mitochondrial damage in HT-22 cells. Azilsartan treatment protected against KA-induced HT-22 cell injury by elevating the viability, reducing the apoptosis, and attenuating mitochondrial damage. Besides, Azilsartan administration activated Sirt3 and Sod2 expression in KA-stimulated HT-22 cells, and Sirt3 depletion partially blocked the impacts of Azilsartan on Sirt3/Sod2 pathway, mitochondrial damage, viability, and apoptosis in HT-22 cells exposed to KA. Collectively, Azilsartan might act as a neuroprotective agent in treating epilepsy through the activation of Sirt3/Sod2 pathway.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581381","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":"Cordycepin Ameliorates Kainic Acid-Induced HT22 Cell Neurotoxicity by Activating GPR120-Mediated Mitophagy","authors":"Yongzhi San,&nbsp;Minghua Wang","doi":"10.1002/dneu.22961","DOIUrl":"https://doi.org/10.1002/dneu.22961","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mitophagy is important for normal neural activity. Epilepsy is intimately linked to neurotoxicity due to mitochondrial dysfunction. Cordycepin (Cor) has been shown to exert neuroprotective effects. This study aims to investigate whether Cor could mitigate neurotoxicity in epilepsy by modulating mitophagy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In vitro, kainic acid (KA) was utilized to induce cytotoxicity in HT22 cell. Cell viability was assessed using the CCK-8 assay, while cell damage was evaluated through an LDH kit. Flow cytometry was used to assess apoptosis. The expressions of G protein-coupled receptor 120 (GPR120), apoptosis, and mitophagy-related proteins were analyzed by western blot. Inflammatory factors and oxidative stress levels were examined by kits. DCFH-DA staining was applied to observe cellular reactive oxygen species (ROS) levels. The three-dimensional coordinates of GPR120 were retrieved from the PDB database, and molecular docking was performed using AutoDock. Immunofluorescence staining was used to observe mitophagy level.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cor significantly attenuated KA-induced HT22 cell viability injury and inflammation, while suppressing ROS and oxidative stress levels. Notably, Cor ameliorated the decrease of mitophagy level observed in HT22 cells treated with KA. GPR120 expression was upregulated following KA treatment and further elevated after adding Cor. Cor could bind to GPR120. Interference with GPR120 reversed the ameliorative effects of Cor on KA-induced mitophagy and cytotoxicity in HT22 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, Cor significantly alleviated KA-induced HT22 cell neurotoxic damage and oxidative stress. This protective effect may be mediated through GPR120-regulated mitophagy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489729","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 Mechanism Behind the Therapeutic Role of Alpha-Tocopherol in Mitigating Hypobaric Hypoxia–Induced Eye Defect in Drosophila melanogaster","authors":"Seekha Naik,&nbsp;Smruti Sudha Biswal,&nbsp;Monalisa Mishra","doi":"10.1002/dneu.22963","DOIUrl":"https://doi.org/10.1002/dneu.22963","url":null,"abstract":"<div>\u0000 \u0000 <p>Hypoxia, or low oxygen levels, is linked to several pathological disorders, including retinopathies. Retina being a metabolically active tissue, low oxygen levels resulted in retinal degradation. The developmental perspective of hypobaric hypoxia (HBH)-induced eye development remains elusive. <i>Drosophila</i> is used as our model organism to investigate the impact of HBH on eye development and alpha-tocopherol as a potential inhibitor. To induce the hypoxic condition, we exposed the <i>Drosophila</i> to hypobaric pressure (120 mbar). Hypoxia induces eye defects in different developmental stages of <i>Drosophila</i> as revealed by histological staining. Biochemical estimation disclosed the presence of reactive oxygen species (ROS) during hypoxia, which led to cellular injury and DNA damage. Quantitative PCR reveals the upregulation of <i>Puf</i>, <i>Wge</i>, and <i>Twr</i> genes and the downregulation of <i>Rh1</i> and <i>Rh6</i> involved in eye development. All these defects are brought back to normal levels after treatment with alpha-tocopherol. This research provides a foundation for understanding ocular developmental problems caused by oxygen deprivation and alpha-tocopherol as a crucial therapeutic approach to the treatment of HBH.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481425","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 Neurodiversity Framework in Medicine: On the Spectrum","authors":"Raul Miranda-Ojeda,&nbsp;Anuksha Wickramasinghe,&nbsp;Georgios Ntolkeras,&nbsp;Isabel Castanho,&nbsp;Walid Yassin","doi":"10.1002/dneu.22960","DOIUrl":"10.1002/dneu.22960","url":null,"abstract":"<div>\u0000 \u0000 <p>The term “neurodiversity” refers to the natural heterogeneity in human neurological functioning, which includes neurodevelopmental differences and other mental health conditions (e.g., autism spectrum disorder [ASD], attention-deficit hyperactivity disorder [ADHD], dyslexia, bipolar disorder, schizophrenia, and depression). This new viewpoint has significant consequences for the future of medicine, specifically in psychiatry, neurology, and neurodevelopmental medicine, as it undermines established notions of these conditions as disorders/diseases that may be healed or corrected. The neurodiversity approach, on the other hand, acknowledges these divergences as natural variations, calling for tailored support and interventions that accommodate individual needs. Neurodiversity could impact current medical perspectives by supporting a shift from pathology to identity. Rather than focusing on the difficulties associated with a specific ailment, the neurodiversity approach stresses the strengths and distinct perspectives that come with neurodivergent identities. This shift has significant consequences for research and therapy by fostering the development of innovative treatments aimed at increasing quality of life and improving functional results. This new perspective advocates including neurodivergent people in all sectors of society, including research, clinical practice, and policymaking, by recognizing, accepting, and integrating natural variances in brain functioning. In this article, we review the development of the neurodiversity movement and propose “The Neurodiversity Framework in Medicine,” which challenges traditional views by recognizing neurological differences as natural variations, advocating for inclusive, person-centered approaches in healthcare.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058015","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":"Investigating the Effect of Capric Acid on Antibiotic-Induced Autism-Like Behavior in Rodents","authors":"Nikhila Shekhar,&nbsp;Ajit Kumar Thakur","doi":"10.1002/dneu.22959","DOIUrl":"10.1002/dneu.22959","url":null,"abstract":"<div>\u0000 \u0000 <p>Owing to the high prevalence of gastrointestinal dysfunction in patients, the gut–brain axis is considered to play a vital role in neurodevelopment diseases. Recent pieces of evidence have pointed to the usage of antibiotics at an early developmental stage to be a causative factor in autism due to its ability to induce critical changes in the gut microbiota. The purpose of the study is to determine the neuroprotective effect of capric acid (CA) on autism in antibiotic-induced gut dysbiosis in rodents. In this study, the effect of CA was observed in penicillin V (31 mg/kg, p.o.) exposed animals by evaluating their autism-like behavioral and biochemical parameters. The establishment of gut dysbiosis was confirmed by 16 RNA sequencing, and behavioral tests were performed. Subsequently, oxidative stress, cytokine levels, and mitochondrial complex activities in the hippocampus and prefrontal cortex were analyzed. It was observed that the administration of penicillin V during the perinatal period produced gut dysbiosis and long-lasting changes in social behavior with symptoms of anxiety and depression and impaired learning and memory. Treatment with penicillin V also produced oxidative stress, mitochondrial dysfunction, and inflammation in the hippocampus and prefrontal cortex. Treatment with CA produced a positive effect on the alterations with maximum effects evident at 400 mg/kg, p.o. through amelioration of behavioral as well as biochemical changes. The current study concluded that CA could act as a likely candidate for the treatment and management of autism via modulation of gut dysbiosis-induced neurobehavioral parameters, oxidative stress, mitochondrial dysfunction, and inflammatory markers.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909598","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":"Elevated Serum Homocysteine Levels Impair Embryonic Neurodevelopment by Dysregulating the Heat Shock Proteins","authors":"Jia Mai,&nbsp;Ling Yang,&nbsp;Min Wang,&nbsp;Jia-Min Deng,&nbsp;Min Min,&nbsp;Hong-Jian Xie,&nbsp;Yong-Mei Jiang,&nbsp;Hua-Qin Sun,&nbsp;Xiao-Juan Liu","doi":"10.1002/dneu.22958","DOIUrl":"10.1002/dneu.22958","url":null,"abstract":"<div>\u0000 \u0000 <p>Observational studies have found that elevated serum homocysteine (Hcy) levels during pregnancy may be associated with the occurrence of neural tube defects (NTDs). However, the effect of Hcy on fetal neural development and its underlying molecular mechanisms remains unclear. To uncover the molecular mechanism, we analyzed the serum Hcy concentration in pregnant women with normal and abnormal pregnancy outcomes and treated zebrafish model embryos with high Hcy. Our findings indicate that elevated serum Hcy levels during pregnancy are associated with adverse pregnancy outcomes. Using the zebrafish model and transcriptome analysis, we found that high Hcy levels led to developmental neural malformations in embryos and affected the expression of key genes at various stages of neural development. Interestingly, deep transcriptome analysis showed that dysregulated heat shock proteins (HSP) might play a key role in high Hcy-mediated alterations in neural development. Importantly, the inhibition of HSP significantly restored the embryonic neuroteratogenic effects induced by high Hcy levels in the zebrafish model. In summary, our findings provide a novel molecular pathogenic mechanism in which ectopic HSP is associated with neural development defects caused by high Hcy levels, suggesting potential prevention and targeted therapies for high Hcy level-related NTDs during pregnancy.</p>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909597","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":"Overexpression of Growth Differentiation Factor 15 Reduces Neuronal Cell Damage Induced by Oxygen-Glucose Deprivation/Reoxygenation via Inhibiting Endoplasmic Reticulum Stress-Mediated Ferroptosis","authors":"Haiming Li,&nbsp;Bin Chen,&nbsp;Zhelin Chen,&nbsp;Jianming Luo,&nbsp;Binyuan Yang","doi":"10.1002/dneu.22957","DOIUrl":"10.1002/dneu.22957","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Growth differentiation factor 15 (GDF15) can be induced under various stress conditions. This study aimed to explore the role of GDF15 in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced HT22 cells. OGD/R was employed to induce the HT22 cell model, and GDF15 expression was upregulated via transfection. Subsequently, the effects on inflammatory factors, oxidative stress markers, apoptosis-related proteins, and ferroptosis markers were detected. Relevant indicators were evaluated using techniques such as ELISA, probes, flow cytometry, and western blotting. Furthermore, changes in these phenotypes under the influence of the endoplasmic reticulum (ER) stress agonist tunicamycin (TM) were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <p>The result showed that GDF15 was significantly up-regulated in OGD/R-treated HT22 cells. Overexpression of GDF15 significantly reduced the levels of inflammatory factors tumor necrosis factor-α, IL (interleukin)-1β, and IL-6, inhibited the production of reactive oxygen species and MDA, and improved activity of superoxide dismutase and GSH-Px. Flow cytometry and western blotting results showed that GDF15 overexpression significantly reduced cell apoptosis, reduced caspase3 activity, and regulated the expression of Bcl2 and Bax. In addition, overexpression of GDF15 reduces the levels of ferroptosis markers by inhibiting ER stress. ER stress inducer TM can reverse the protective effects of GDF15 overexpression and promote inflammation, oxidative stress, and apoptosis. This study shows that overexpression of GDF15 reduces OGD/R-induced HT22 cell damage, and ER stress-mediated ferroptosis is included in the regulatory mechanisms. This provides a theoretical basis for GDF15 as a new target for the treatment of cerebral ischemia-reperfusion injury.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876614","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":"Novel Transgenic Zebrafish Lines to Study the CHRNA3-B4-A5 Gene Cluster","authors":"Yuanqi Hua,&nbsp;Judith Habicher,&nbsp;Matthias Carl,&nbsp;Remy Manuel,&nbsp;Henrik Boije","doi":"10.1002/dneu.22956","DOIUrl":"10.1002/dneu.22956","url":null,"abstract":"<p>Acetylcholine (ACh), a vital neurotransmitter for both the peripheral (PNS) and central nervous systems (CNS), signals through nicotinic ACh receptors (nAChRs) and muscarinic ACh receptors (mAChR). Here, we explore the expression patterns of three nAChR subunits, <i>chrna3</i>, <i>chrnb4</i>, and <i>chrna5</i>, which are located in an evolutionary conserved cluster. This close genomic positioning, in a range of vertebrates, may indicate co-functionality and/or co-expression. Through novel transgenic zebrafish lines, we observe widespread expression within both the PNS and CNS. In the PNS, we observed expression of <i>chrna3^tdTomato</i>, <i>chrnb4^eGFP</i>, and <i>chrna5</i>^tdTomato in the intestinal enteric nervous system; <i>chrna5^tdTomato</i> and <i>chrnb4^eGFP</i> in sensory ganglia of the lateral line; and <i>chrnb4^eGFP</i> in the ear. In the CNS, the expression of <i>chrnb4^eGFP</i> and <i>chrna5</i>^tdTomato was found in the retina, all three expressed in diverse regions of the brain, where a portion of <i>chrna3^tdTomato</i> and <i>chrnb4^eGFP</i> cells were found to be inhibitory efferent neurons projecting to the lateral line. Within the spinal cord, we identify distinct populations of <i>chrna3^tdTomato</i>-, <i>chrnb4^eGFP</i>-, and <i>chrna5</i>^tdTomato-expressing neurons within the locomotor network, including <i>dmrt3a</i>-expressing interneurons and <i>mnx1</i>-expressing motor neurons. Notably, three to four primary motor neurons per hemisegment were labeled by both <i>chrna3^tdTomato</i> and <i>chrnb4^eGFP</i>. Interestingly, we identified an sl-type secondary motor neuron per hemisegement that strongly expressed <i>chrna5</i>^tdTomato and co-expressed <i>chrnb4^eGFP</i>. These transgenic lines provide insights into the potential roles of nAChRs within the locomotor network and open avenues for exploring their role in nicotine exposure and addiction in a range of tissues throughout the nervous system.</p>","PeriodicalId":11300,"journal":{"name":"Developmental Neurobiology","volume":"85 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dneu.22956","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}