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Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration Research 2025年第09期 2624-2632页

作者： Jangampalli Adi Pradeepkiran Priyanka Rawat Arubala P.Reddy Erika Orlov P.Hemachandra Reddy Department of Internal Medicine Texas Tech University Health Sciences Center Department of Nutritional Sciences College of Human SciencesTexas Tech University Department of Pharmacology & Neuroscience Texas Tech University Health Sciences Center Department of Neurology Texas Tech University Health Sciences Center Department of Speech Language and Hearing SciencesTexas Tech University Health Sciences Center Department of Public Health Texas Tech University Health Sciences Center

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl) methylphosphonate(DDQ) on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau) *** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau) were seen to display increased levels of synaptophysin,MAP-2,and β-***,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic *** findings conclude that mTa u-HT22(Alzheimer's disease) cells treated with DDQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

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Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration Research 2025年第9期20卷 2624-2632页

作者： Jangampalli Adi Pradeepkiran Priyanka Rawat Arubala P.Reddy Erika Orlov PHemachandra Reddy Department of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA Department of Nutritional Sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA Department of Pharmacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA Department of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA Department of Speech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA Department of Public Health Texas Tech University Health Sciences CenterLubbockTXUSA

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)*** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-***,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule

Novel heterozygous USH1C mutation impacts hair cell mechanotransduction and causes progressive hearing loss

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Science Bulletin 2024年第2期69卷 167-172页

作者： Yanyan Jia Gaogan Jia Luo Guo Nan Song Yu-Meng Wang Luoying Jiang Yilai Shu Yan Chen Shujia Zhu Huawei Li Wenyan Li ENT Institute and Otorhinolaryngology Department of Eye&ENT Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200031China Institutes of Biomedical Sciences Fudan UniversityShanghai 200032China NHC Key Laboratory of hearing Medicine(Fudan University) Shanghai 200031China The Institutes of Brain Science and the Collaborative Innovation center for Brain Science Fudan UniversityShanghai 200032China Shanghai center for Brain Science and Brain-Inspired Intelligence Technology Shanghai 201210China Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Department of Cardiology and Institute for Developmental and Regenerative Cardiovascular MedicineXinhua Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200092China

hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss cases[2,3].These genetic changes result in a wide variety of clinical manifestations,ranging from nonsyndromic hearing loss(NSHL)to over 400 syndromes involving hearing loss and from mild adult-onset hearing loss to profound congenital deafness,covering the entire spectrum of Mendelian inheritance.

关键词： mec hearing approximate

A preliminary study of the mechanism of compound hearing loss caused by ototoxic drugs combined with impulse noise

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iLABMED 2024年第1期2卷 38-52页

作者： Xin Qiu Qing‐qing Jiang Wei‐wei Guo Ning Yu Shi‐ming Yang Senior Department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of hearing and Balance Science BeijingChina National Clinical Research center for Otolaryngologic Diseases BeijingChina Key Laboratory of hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of hearing Impairment Prevention and Treatment BeijingChina Chinese PLA Medical School BeijingChina

Background:hearing loss(HL)is becoming increasingly common and is more commonly caused by noise,ototoxic substances,or a combination of ototoxic ***,so far,few studies have examined the mechanism by which compound factors cause *** only relevant study is about occupational ototoxic substances combined with environmental noise at 85-110 dB *** this study,to address the shortcomings of existing research,we innovatively focused on HL induced by loud noise(impulse noise,>160 dB SPL)combined with common ototoxic *** aim of this study was to establish and validate a mature animal model,and then to compare the characteristics of audiology,pathomorphology and molecular features,and to preliminarily predict pathogenesis in compound *** and Methods:We selected guinea pigs to construct in vivo HL model groups for different extents of exposure,including a blank control group,a single-drug group,a single-impulse noise group,and a compound *** animal model of the mature compound HL group was established using gentamicin combined with impulse *** then performed audio-logical and pathological *** analyzed the auditory brainstem response(ABR),pathological morphology of the cochlea,and molecules(including important self-radicals,cytokines,and apoptosis signal trans-duction pathway proteins in the pathogenesis of drug-and noise-induced HL),compared the effect of different extents of exposure on HL,and preliminarily predict the pathogenic mechanism of compound ***:Four groups of animal models were established successfully and verified by audiology and *** audiology,there were no sig-nificant differences in the ABR thresholds before exposure(p>0.05),but differences emerged among the groups after ***,after 3,7,and 14 days of exposure,there were significant differences in the ABR thresholds between the compound group and both the drug and noise groups(p<0.01),and after 14 days,the HL of the compoun

关键词： auditory brainstem response gentamicin hearing loss impulse noise molecular mechanisms pathomorphology

Evaluation of the Effectiveness of“5E”Comprehensive Injury Prevention Strategy for Fall Prevention Among the Rural Elderly—Six Pilot Villages,Yunnan Province and Chongqing Municipality,China,2018–2023

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China CDC weekly 2024年第14期6卷 277-281页

作者： Fujin Sun Rong Luo Hui Han National center for Women and Children’s Health Chinese Center for Disease Control and PreventionBeijingChina

What is already known about this topic?The mortality rate and disease burden associated with falls among the elderly in China are on the *** can play a crucial role in preventing and managing *** is added by this report?The application of the“5E”injury prevention strategy led to a decrease in both the occurrence of falls and the likelihood of subsequent *** physical activity and maintaining a positive outlook were identified as protective measures against falls,while sleep issues and hearing impairment were found to increase the risk of *** are the implications for public health practice?The group-based comprehensive intervention strategy is crucial as it offers an innovative intervention model and empirical evidence for decreasing fall rates among elderly individuals living in rural areas.

关键词： Chongqing Rural prevention

Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

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Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： Xihang Chen Zhifeng Chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi Shi Wei Chen Shiming Yang Senior Department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of hearing and Balance Science BeijingChina National Clinical Research center for Otolaryngologic Diseases BeijingChina Key Laboratory of hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of hearing Impairment Prevention and Treatment BeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Otolaryngology Head and Neck Surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

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hearing Loss and Depressive Symptoms Among Community-Dwelling Older Adults-Liaoning,Henan,and Guangdong Provinces,China,2019-2020

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China CDC weekly 2024年第32期6卷 811-815,I0002页

作者： Ran An Lu Cui Liyuan Yang Han Zhang Shige Qi Haoyan Guo National center for Chronic and Noncommunicable Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina School of Public Health Capital Medical UniversityBeijingChina Chengnan Community Health Service center of Changping District BeijingChina National Institute for Nutrition and Health Chinese Center for Disease Control and PreventionBeijingChina

Summary What is already known about this topic?More than half of Chinese older adults over 60 are suffering from hearing loss(HL),which might increase the risk of depressive *** is added by this report?The results indicated a significant association between severe or profound HL and depressive symptoms,characterized by notable age and gender disparities,particularly among women aged 60–74 years *** are the implications for public health practice?Timely intervention and treatment for elderly individuals with HL,particularly younger female elders suffering from severe or profound HL,are pivotal in reducing depressive symptom rates and are key policy considerations.

关键词： younger policy suffering

Sino-nasal outcome Test-22 and Lund–Mackay CT score to select endoscopic sinus surgery in chronic rhinosinusitis

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第3期10卷 200-205页

作者： Abolfazl Taheri Sajad Hasani Mohsen Saberi Esfeedvajani Masoumeh Saeedi Reyhane Abolghasemi New hearing Technologies Research center Clinical Sciences InstituteBaqiyatallah University of Medical SciencesTehranIran Department of Otorhinolaryngology Head and Neck SurgeryFaculty of MedicineBaqiyatallah University of Medical SciencesTehranIran Faculty of Medicine Baqiyatallah University of Medical SciencesTehranIran Department of Community Medicine MedicineQuran and Hadith Research CenterFaculty of MedicineBaqiyatallah University of Medical SciencesTehranIran

Objectives:Chronic rhinosinusitis is one of the common diseases that cause morbidity and affects a person's quality of *** tried to provide a more appropriate and effective approach to selecting patients for endoscopic sinus ***:The study population is chronic rhinosinusitis children referred to the ear,nose,and throat clinic of two general hospitals in Tehran,Iran,who have previously undergone sufficient drug treatment and have not *** Lund–Mackay score is calculated by examining the computed tomography(CT)*** Sino-nasal Outcome Test-22(SNOT-22)questionnaire was provided to the patients before the operation,after the operation,and 3 and 6 months later in the ***:Before the operation,the most SNOT-22 score people were in the range of 40–59 *** SNOT-22 score before the operation is significantly different from 3 and 6 months after the *** highest frequency of Lund–Mackay CT(LMCT)scan score was in the range of 18–23 *** LMCT scan score did not show any significant relationship with the SNOT-22 score before surgery,3 months,and 6 months after *** to aspirin had a significant relationship with SNOT-22 scores and the history of asthma and nasal polyps had a significant relationship with the preoperative LMCT scan ***:The LMCT scan scoring system cannot be a good measure of chronic rhinosinusitis severity or the prognosis of patients after *** SNOT-22 questionnaire can be used as a predictive tool to help the doctor and the patient in deciding to operate and the possibility of obtaining a relative recovery.

关键词： endoscopic surgical procedures Lund–Mackay CT score sinusitis SNOT-22 questionnaire

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Ca^(2+) binding to the C_(2)E domain of otoferlin is required for hair cell exocytosis and hearing

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Protein & Cell 2024年第4期15卷 305-312页

作者： Han Chen Mehar Monga Qinghua Fang Loujin Slitin Jakob Neef Shashank S.Chepurwar Regina Célia Mingroni Netto Karina Lezirovitz Alfredo Tabith,Jr. Fritz Benseler Nils Brose Kathrin Kusch Carolin Wichmann Nicola Strenzke Barbara Vona Julia Preobraschenski Tobias Moser Institute for Auditory Neuroscience and InnerEarLab University Medical Center Göttingen37075 GöttingenGermany Collaborative Research center 889 University of Göttingen37075 GöttingenGermany Auditory Neuroscience and Synaptic Nanophysiology Group Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Göttingen Graduate center for Neurosciences Biophysics and Molecular BiosciencesUniversity of Göttingen37075 GöttingenGermany Biochemistry of Membrane Dynamics Group Institute for Auditory NeuroscienceUniversity Medical Center Göttingen37075 GöttingenGermany Molecular Architecture of Synapses Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany center for Biostructural Imaging of Neurodegeneration University Medical Center Göttingen37075 GöttingenGermany Auditory Systems Physiology Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Departamento de Genética e Biologia Evolutiva Centro de Pesquisas sobre o Genoma Humano e Células-TroncoInstituto de BiociênciasUniversidade de São PauloSão Paulo 05508-220Brazil Laboratório de Otorrinolaringologia/LIM32 Faculdade de MedicinaHospital das ClínicasUniversidade de São PauloSão PauloSP 05508-220Brazil DERDIC Pontifícia Universidade Católica de São PauloSão Paulo 05508-220Brazil Department of Molecular Neurobiology Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Multiscale Bioimaging Cluster of Excellence(MBExC) University of Göttingen37075 GöttingenGermany Functional Auditory Genomics Group Auditory Neuroscience and Optogenetics LaboratoryGerman Primate Center37077 GöttingenGermany hearing Genomics Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Institute of Human Genetics University Medical Center Göttingen37075 GöttingenGermany

Dear Editor,Afferent synapses of cochlear inner hair cells(IHCs)employ a unique molecular machinery(see extended background in Supplementary Materials).Otoferlin is a key player in this machinery and its defects cause human auditory synaptopathy(Moser and Starr,2016).Otoferlin,a tail-anchored(Vogl et al.,2016)multi-C_(2)-domain protein(Fig.1Ai)specific to hair cells(Roux et al.,2006),is a member of the ferlin protein family involved in membrane trafficking and repair that are of major disease relevance(Pangršičet al.,2012),also see Supplementary *** is distributed broadly within IHCs(Fig.2Ai-Aiii;Pangrsic et al.,2010;Roux et al.,2006).

关键词： auditory hair

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