Neurochemistry international最新文献_第3页

Beyond plaques and tangles: The role of immune cell dysfunction in Alzheimer's disease

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-02-14 DOI: 10.1016/j.neuint.2025.105947

Nasif Hussain , Mohd Moin Khan , Ayushi Sharma , Rakesh K. Singh , Rizwan Hasan Khan

引用次数: 0

Neuro-nutraceuticals: Emerging molecular and functional insights into how natural products improve brain health

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-02-13 DOI: 10.1016/j.neuint.2025.105948

K.P. Mohanakumar (Director, Professor of Biological Sciences) , Catarina Rendeiro (Assistant Professor in Nutritional Sciences) , Philip M. Beart (formerly Professor)

{"title":"Neuro-nutraceuticals: Emerging molecular and functional insights into how natural products improve brain health","authors":"K.P. Mohanakumar (Director, Professor of Biological Sciences) , Catarina Rendeiro (Assistant Professor in Nutritional Sciences) , Philip M. Beart (formerly Professor)","doi":"10.1016/j.neuint.2025.105948","DOIUrl":"10.1016/j.neuint.2025.105948","url":null,"abstract":"<div><div>The editors in assembling this Special Issue, “Neuro-nutraceuticals: Emerging Molecular and Functional Insights into how Natural Products Improve Brain Health”, sought to advance our understanding of how such chemical entities alone or in group maintain brain metabolism and homeostasis so that neurons, glia and endothelial cells are healthy during development, ageing and in neuropathologies. The growth of interest in neuro-nutraceuticals and all aspects of their actions relevant to the health of the nervous system continues to amaze all. This Special Issue # 4 contains 39 articles, and we sought to highlight in this Special Issue important new advances and key issues pertinent to future clinical application of neuro-nutraceuticals. The diversity of topics covered is quite broad and includes significant articles on enteric microbiome and brain health. The Editors have tried to provide an up-to-date account of how nutraceuticals work at the molecular and cellular level, and what are the known molecular targets that ultimately can be leveraged clinically to enable the brain to function better. With respect to brain ailments and treatments, single molecule effects, and a therapeutic group of molecules from dietary herbals are discussed in this Special Issue.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"185 ","pages":"Article 105948"},"PeriodicalIF":4.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Temporal and spatial expression of Phosphodiesterase-4B after sciatic nerve compression in rats and its mechanism of action on sciatic nerve repair

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-02-04 DOI: 10.1016/j.neuint.2025.105940

Yufei Wang , Youfei Zhou , Jinhao Liu , Chen Liu , Zirui Li , Xuehua Sun

{"title":"Temporal and spatial expression of Phosphodiesterase-4B after sciatic nerve compression in rats and its mechanism of action on sciatic nerve repair","authors":"Yufei Wang , Youfei Zhou , Jinhao Liu , Chen Liu , Zirui Li , Xuehua Sun","doi":"10.1016/j.neuint.2025.105940","DOIUrl":"10.1016/j.neuint.2025.105940","url":null,"abstract":"<div><h3>Background</h3><div>Macrophage phenotype transformation is vital in sciatic nerve injury. The study of biomolecule expression and its impact on macrophage phenotype transformation is a current research focus.</div></div><div><h3>Material and methods</h3><div>We created a rat model of sciatic nerve compression injury to examine the expression of PDE4B and the distribution of M1 and M2 macrophages over time and their relationship. We confirmed the effect of inhibiting PDE4B expression on macrophage phenotype changes and its role in sciatic nerve injury repair. The experiments consisted of immunofluorescence, western blotting, HE staining, TEM, and behavioral evaluation. Investigate in vivo experiment results with RAW264.7 cells in vitro. PDE4B knockdown lentivirus was transfected into RAW264.7 cells and stimulated with LPS and IFN-γ. We assessed CD86 and CD206 expression using flow cytometry and western blot. The relationship between PDE4B and the TLR4/NF-κB pathway was studied.</div></div><div><h3>Results</h3><div>PDE4B peaked on day 7 after surgery, alongside the highest M1 macrophages count. PDE4B and M1 macrophages decreased, and M2 macrophages increased. PDE4B inhibition reduced M1 macrophages, increased M2 macrophages, suppressed inflammation, and promoted sciatic nerve repair while alleviating pain. In vitro experiments confirmed that PDE4B regulated macrophage phenotype via the TLR4/NF-κB pathway. Inhibiting PDE4B disrupted this pathway and promoted M2 macrophage transformation.</div></div><div><h3>Conclusions</h3><div>In the sciatic nerve injury, PDE4B expression is linked to the M1 macrophage phenotype. Low PDE4B expression facilitates the M1 to M2 macrophage transformation and supports sciatic nerve repair. The TLR4/NF-κB pathway is involved in this process.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"185 ","pages":"Article 105940"},"PeriodicalIF":4.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cerebellum KCC2 protein expression plasticity in response to cerebral cortical stroke

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-02-03 DOI: 10.1016/j.neuint.2025.105939

Shamseldin Metwally , Okan Capuk , Jun Wang , Mohammad Iqbal H. Bhuiyan , Qiang Li , Kathiravan Kaliyappan , Bo Chen , Daryl Fields , Dandan Sun

{"title":"Cerebellum KCC2 protein expression plasticity in response to cerebral cortical stroke","authors":"Shamseldin Metwally , Okan Capuk , Jun Wang , Mohammad Iqbal H. Bhuiyan , Qiang Li , Kathiravan Kaliyappan , Bo Chen , Daryl Fields , Dandan Sun","doi":"10.1016/j.neuint.2025.105939","DOIUrl":"10.1016/j.neuint.2025.105939","url":null,"abstract":"<div><h3>Background</h3><div>Recent evidence suggests extra-cortical adaptations within the cerebellum may contribute to motor recovery in patients with cortical ischemic strokes. The molecular/cellular adaptations enabling this effect to have not been identified. Chloride transport proteins (NKCC1 and KCC2) are important regulators of neuronal transmission and may underlie adaptive changes following ischemic stroke.</div></div><div><h3>Objective</h3><div>Examine changes in cerebellar NKCC1 and KCC2 protein expression following cortical ischemic stroke.</div></div><div><h3>Methods</h3><div>Adult C57BL/6J male mice underwent sham or the left middle cerebral artery occlusion (tMCAo)-induced ischemic stroke. Changes of NKCC1 and KCC2 proteins within the deep cerebellar nuclei (DCN) were assessed by immunofluorescence staining.</div></div><div><h3>Results</h3><div>tMCAo induced selective infarct lesion in the left striatum and cortex of the stroke mice but not in other brain regions including cerebellum. The inwardly directed chloride transporter NKCC1 was equivocally expressed within bi-hemispheric DCN of both sham control and stroke mice. In contrast, the outwardly directed chloride transporter KCC2 protein expression was significantly higher in the bi-hemispheric DCN of stroke brains, compared to sham controls. Double immunostaining analysis revealed a statistically significant increase in KCC2 intensity within VGLUT-1<sup>+</sup> neurons of the ipsilateral DCN of the stroke mice, but not in the VGAT<sup>+</sup> neurons.</div></div><div><h3>Conclusions</h3><div>Ischemic cortical stroke stimulates KCC2 protein expression in the DCN VGLUT-1<sup>+</sup> neurons, without a change in NKCC1 protein expression.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"184 ","pages":"Article 105939"},"PeriodicalIF":4.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CB1 receptor signaling: Linking neuroplasticity, neuronal types, and mental health outcomes

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-02-02 DOI: 10.1016/j.neuint.2025.105938

Qianqian Gao , Muhammad Asim

{"title":"CB1 receptor signaling: Linking neuroplasticity, neuronal types, and mental health outcomes","authors":"Qianqian Gao , Muhammad Asim","doi":"10.1016/j.neuint.2025.105938","DOIUrl":"10.1016/j.neuint.2025.105938","url":null,"abstract":"<div><div>The endocannabinoid system (ECS) is crucial in the pathophysiology of mental disorders. Historically, cannabis has been utilized for centuries to mitigate symptoms of anxiety and depression; however, the precise role of cannabinoids in these conditions has only recently garnered extensive research attention. Despite the growing body of literature on the ECS and its association with mental health, several critical questions remain unresolved. This review primarily focuses on cannabinoid CB<sub>1</sub> receptors (CB<sub>1</sub>R), providing an examination of their regulatory roles in states related to mental disorders. Evidence suggests that CB<sub>1</sub>R distribution occurs among various neuronal types, astrocytes, and subcellular membranes across multiple brain regions, potentially exhibiting both analogous and antagonistic effects. Additionally, various forms of stress have been shown to produce divergent impacts on CB<sub>1</sub>R signaling pathways. Furthermore, numerous CB<sub>1</sub>R agonists demonstrate biphasic, dose-dependent effects on anxiety and depression; specifically, low doses may exert anxiolytic effects, while higher doses can induce anxiogenic responses, a phenomenon observed in both rodent models and human studies. We also discuss the diverse underlying mechanisms that mediate these effects. We anticipate that this review will yield valuable insights into the role of CB<sub>1</sub>R in mental disorders and provide a framework for future research endeavors on CB<sub>1</sub>R and the ECS. This knowledge may ultimately inform therapeutic strategies aimed at alleviating symptoms associated with mental health conditions.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"184 ","pages":"Article 105938"},"PeriodicalIF":4.4,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Understanding the intricacies of cellular mechanisms in remyelination: The role of circadian rhythm 理解髓鞘再生中细胞机制的复杂性：昼夜节律的作用。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-02-01 DOI: 10.1016/j.neuint.2025.105929

Yufen Tang , Lu Zhang , Peng Huang , Zhou She , Senlin Luo , Hong Peng , Yuqiong Chen , Jinwen Luo , Wangxin Duan , Yangyang Xiao , Lingjuan Liu , Liqun Liu

{"title":"Understanding the intricacies of cellular mechanisms in remyelination: The role of circadian rhythm","authors":"Yufen Tang , Lu Zhang , Peng Huang , Zhou She , Senlin Luo , Hong Peng , Yuqiong Chen , Jinwen Luo , Wangxin Duan , Yangyang Xiao , Lingjuan Liu , Liqun Liu","doi":"10.1016/j.neuint.2025.105929","DOIUrl":"10.1016/j.neuint.2025.105929","url":null,"abstract":"<div><div>The term “circadian rhythm” refers to the 24-h oscillations found in various physiological processes in organisms, responsible for maintaining bodily homeostasis. Many neurological diseases mainly involve the process of demyelination, and remyelination is crucial for the treatment of neurological diseases. Current research mainly focuses on the key role of circadian clocks in the pathophysiological mechanisms of multiple sclerosis. Various studies have shown that the circadian rhythm regulates various cellular molecular mechanisms and signaling pathways involved in remyelination. The process of remyelination is primarily mediated by oligodendrocyte precursor cells (OPCs), oligodendrocytes, microglia, and astrocytes. OPCs are activated, proliferate, migrate, and ultimately differentiate into oligodendrocytes after demyelination, involving many key signaling pathway and regulatory factors. Activated microglia secretes important cytokines and chemokines, promoting OPC proliferation and differentiation, and phagocytoses myelin debris that inhibits remyelination. Astrocytes play a crucial role in supporting remyelination by secreting signals that promote remyelination or facilitate the phagocytosis of myelin debris by microglia. Additionally, cell-to-cell communication via gap junctions allows for intimate contact between astrocytes and oligodendrocytes, providing metabolic support for oligodendrocytes. Therefore, gaining a deeper understanding of the mechanisms and molecular pathways of the circadian rhythm at various stages of remyelination can help elucidate the fundamental characteristics of remyelination and provide insights into treating demyelinating disorders.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"183 ","pages":"Article 105929"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A topographic approach to the markers of macrophage/microglia and other cell types in high grade glioma 高级别胶质瘤中巨噬细胞/小胶质细胞和其他细胞类型标记物的地形学研究。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-02-01 DOI: 10.1016/j.neuint.2024.105922

Lucia Lisi , Alessandro Olivi , Gabriella Maria Pia Ciotti , Salvatore Marino , Chiara Ferraro , Grazia Menna , Maria Martire , Giovanni Pennisi , Pierluigi Navarra , Giuseppe Maria della Pepa

{"title":"A topographic approach to the markers of macrophage/microglia and other cell types in high grade glioma","authors":"Lucia Lisi , Alessandro Olivi , Gabriella Maria Pia Ciotti , Salvatore Marino , Chiara Ferraro , Grazia Menna , Maria Martire , Giovanni Pennisi , Pierluigi Navarra , Giuseppe Maria della Pepa","doi":"10.1016/j.neuint.2024.105922","DOIUrl":"10.1016/j.neuint.2024.105922","url":null,"abstract":"<div><div>In glioblastoma, glioma-associated microglia/macrophages (GAMs) represent the major population of tumor infiltrating cells, with up to one half of the cells of the tumor mass. Recent studies have shown that microglia are involved in the maintenance of immunological homeostasis and protection against autoimmunity. However, despite the growing body of evidence on the topic, many aspects are yet to be clarified. In our study, 3 different situations emerged concerning the markers of microglial/macrophage-related and other cell types in GBM patients: i) most of the markers (IBA1, TMEM119, CD206 and CD86) show an ascending gradient from the tumor center to the non-tumor/healthy area of the brain; ii) one marker (CD204) shows a descending gradient, going from the center of the tumor to the non-tumor/healthy brain area; iii) two markers (CD163 and P2RY12) show no gradient. These observations support the idea that the magnitude of the diverted inflammation is a ‘extensive’ rather than a ‘local’ phenomenon and that could possibly play a role in disease resistance and relapse.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"183 ","pages":"Article 105922"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Previous strength training attenuates ouabain-induced bipolar disorder-related behaviors and memory deficits in rats: Involvement of hippocampal ERK/CREB and PI3K/AKT/mTOR pathways 先前的力量训练减弱了大鼠的维卡因诱导的双相情感障碍相关行为和记忆缺陷：海马ERK/CREB和PI3K/AKT/mTOR通路的参与

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-02-01 DOI: 10.1016/j.neuint.2024.105919

Luan Machado Maidana , Jozyê Milena da Silva Guerra , Adson Souza-Pereira , Marizabel Parente Lins , Mayckel Jean Moreira-Silva , Eduarda Goulart Paiva , Douglas Buchmann Godinho , Luis Fernando Freire Royes , Leonardo Magno Rambo

{"title":"Previous strength training attenuates ouabain-induced bipolar disorder-related behaviors and memory deficits in rats: Involvement of hippocampal ERK/CREB and PI3K/AKT/mTOR pathways","authors":"Luan Machado Maidana , Jozyê Milena da Silva Guerra , Adson Souza-Pereira , Marizabel Parente Lins , Mayckel Jean Moreira-Silva , Eduarda Goulart Paiva , Douglas Buchmann Godinho , Luis Fernando Freire Royes , Leonardo Magno Rambo","doi":"10.1016/j.neuint.2024.105919","DOIUrl":"10.1016/j.neuint.2024.105919","url":null,"abstract":"<div><div>Bipolar disorder (BD) is a central nervous system condition that is typified by fluctuations in mood, oscillating between depressive and manic, and/or hypomanic episodes. The objective of this study was to test the hypothesis that strength training may act as a potent protector against behavioral and neurochemical changes induced by BD. A strength training protocol was performed with adult male Wistar rats, and seven days following the conclusion of training, a single ouabain injection was administered. Following ouabain administration, the animals were subjected to behavioral tests after the seventh (manic period) and fourteenth (depressive period) days. Subsequently, rats were euthanized and the hippocampus was collected for western blotting assays. We demonstrated that strength training provided protection against ouabain-induced behavioral changes, both during the manic and depressive periods, including increased locomotor activity, risk-taking and aggressive-like behaviors, and impaired memory performance. Furthermore, physical training protected against ouabain-induced decrease of neurogenesis/neuroplasticity-related pathways, including BDNF/TrKB/ERK/CREB and PI3K/AKT/mTOR/p70S6K. These findings suggest that strength training has a protective effect, attenuating or preventing BD-induced deficits, and may have therapeutic potential as an adjuvant treatment for this patient population in the future.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"183 ","pages":"Article 105919"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Celecoxib paradoxically induces COX-2 expression and astrocyte activation through the ERK/JNK/AP-1 signaling pathway in the cerebral cortex of rats 塞来昔布通过ERK/JNK/AP-1信号通路矛盾地诱导大鼠大脑皮层COX-2表达和星形胶质细胞活化。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-02-01 DOI: 10.1016/j.neuint.2024.105926

Kai-Che Wei , Jun-Ting Lin , Chia-Ho Lin

{"title":"Celecoxib paradoxically induces COX-2 expression and astrocyte activation through the ERK/JNK/AP-1 signaling pathway in the cerebral cortex of rats","authors":"Kai-Che Wei , Jun-Ting Lin , Chia-Ho Lin","doi":"10.1016/j.neuint.2024.105926","DOIUrl":"10.1016/j.neuint.2024.105926","url":null,"abstract":"<div><div>Previous studies have shown that celecoxib or NSAID may paradoxically induce cyclooxygenase-2 (COX-2) expression and trigger inflammation-like responses in airway smooth muscle cells and renal mesangial cells. Despite the extensive research on celecoxib, its atypical biological effect on the induction of COX-2 in astroglial cells within the central nervous system (CNS) remains unexplored. In the present study, we investigated the impact of celecoxib on COX-2 and Glial Fibrillary Acidic Protein (GFAP) expression and explored the mechanisms underlying celecoxib-regulated COX-2 expression in cortical astrocytes of rats.</div><div>Cortical astrocytes were treated with celecoxib (20 μM) for 24 h, resulting in a significant increase in COX-2 expression and up-regulation of GFAP, a marker of astrocyte activation, and the COX-2 induced by celecoxib is functionally active in prostaglandin E2 (PGE2) synthesis. Celecoxib also enhanced LPS-induced COX-2 expression, but its ability to inhibit PGE2 synthesis decreased at higher concentrations. Celecoxib induced phosphorylation of Extracellular signal-regulated Kinase (ERK) and c-Jun N-terminal Kinase (JNK) but not p38 Mitogen-Activated Protein Kinase (p38 MAPK), and inhibition of activity of ERK and JNK by U0126 and SP600125 effectively blocked COX-2 and GFAP induction by celecoxib. Celecoxib increased the accumulation of transcription factor AP-1 (composed of phosphorylated c-Jun and c-fos) in the nucleus. Inhibition of AP-1 activity with SR11302 significantly prevented celecoxib-induced COX-2 and GFAP expression. Additionally, the inhibiting activity of ERK and JNK can effectively suppress AP-1 expression and activity induced by celecoxib.</div><div>These findings demonstrated that celecoxib induces COX-2 expression and astrocyte activation through the ERK/JNK/AP-1 signaling pathway, highlighting its potential effect in modulating inflammatory responses in the central nervous system.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"183 ","pages":"Article 105926"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vitro effects of recombinant human Neuritin on hair cell recovery post-gentamicin injury in SC lineage-tracing models: Involvement of notch and FGFR signaling 重组人神经素对SC谱系追踪模型中庆大霉素损伤后毛细胞恢复的体外影响：Notch和FGFR信号通路的参与

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-02-01 DOI: 10.1016/j.neuint.2025.105935

Haiyan Wang , Xue Zhang , Fei Gui , Xiaopin Sun , Rong Chen , Guanwu Yin , Yu Hong , Jin Huang , Lei Yang

{"title":"In vitro effects of recombinant human Neuritin on hair cell recovery post-gentamicin injury in SC lineage-tracing models: Involvement of notch and FGFR signaling","authors":"Haiyan Wang , Xue Zhang , Fei Gui , Xiaopin Sun , Rong Chen , Guanwu Yin , Yu Hong , Jin Huang , Lei Yang","doi":"10.1016/j.neuint.2025.105935","DOIUrl":"10.1016/j.neuint.2025.105935","url":null,"abstract":"<div><div>Hair cell (HC) loss, frequently induced by ototoxic agents such as gentamicin, leads to irreversible hearing loss. Because of the restricted regenerative capabilities of the mammalian inner ear, the exploration of therapeutic strategies to restore damaged HCs is critically needed. Recombinant human Neuritin (rhNeuritin), a neurotrophic factor with established roles in promoting cell survival and regeneration across various systems, presents itself as a promising therapeutic candidate for HC repair. In this study, we elucidate the protective effects of rhNeuritin on injured HCs and its capacity to facilitate HC regeneration post-damage. Through the use of cochlear Supporting Cell (SC) lineage-tracing models in neonatal mice, we demonstrate that SC <em>trans</em>-differentiation serves as the origin of HC regeneration following damage. Simultaneously, we uncover that rhNeuritin potentiates the proliferation of SC precursor cells. Mechanistic insights reveal that rhNeuritin-induced cochleae exhibit downregulation of the critical Notch pathway mediator, Hes1, and upregulation of the essential FGFR pathway component Erm, which together may underpin HC regeneration and the proliferation of SC precursors. Notably, rhNeuritin demonstrates significant preservation of HC structural integrity. These findings collectively highlight the therapeutic potential of rhNeuritin in addressing hearing loss resulting from HC damage, thereby opening a new avenue for the restoration of auditory function.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"183 ","pages":"Article 105935"},"PeriodicalIF":4.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0