Molecular Neurobiology最新文献_第4页

Molecular Characterization and Expression of Lactoferrin Receptor (LfR) in Different Regions of the Brain Responding to Lactoferrin Intervention. 乳铁蛋白受体（LfR）在对乳铁蛋白干预做出反应的大脑不同区域的分子特征和表达。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-08-24 DOI: 10.1007/s12035-024-04378-z

Siqi Wang, Nai Zhang, Bowen Jiang, Bo Lönnerdal, Yue Chen, Bing Wang

{"title":"Molecular Characterization and Expression of Lactoferrin Receptor (LfR) in Different Regions of the Brain Responding to Lactoferrin Intervention.","authors":"Siqi Wang, Nai Zhang, Bowen Jiang, Bo Lönnerdal, Yue Chen, Bing Wang","doi":"10.1007/s12035-024-04378-z","DOIUrl":"10.1007/s12035-024-04378-z","url":null,"abstract":"Lactoferrin (LF), an iron-binding glycoprotein rich in human milk, promotes neurodevelopment and cognition, but whether it acts through the LF receptor (LfR) and its expression profile in the brain remains unknown. We characterized 972 bp of piglet brain LfR cDNA and found LfR mRNA was expressed all brain regions being highest in the frontal lobe, followed by parietal lobe, brainstem, occipital lobe, cingulate gyrus, subventricular zone, olfactory bulb, hippocampus, amygdala, cerebellum, and thalamus. LfR mRNA and protein in different regions of the brain responded to low (155 mg/kg/day) and high (285 mg/kg/day) LF supplementation of piglets from postnatal days 3 to 38. By postnatal day 39, the low LF diet significantly increased LfR protein expression in the occipital lobe compared to controls, but not the high LF diet. LfR protein in the subventricular zone of the high LF group was 42% and 38% higher than that of the low LF group and controls, respectively. There was a trend for a dose-response relationship between LF intervention and LfR protein expression only in the prefrontal and parietal lobes. LF supplementation significantly improved piglet working memory for a difficult task, which was positively correlated with LfR protein in the prefrontal, parietal, and occipital lobes, but no dose response. Brain LfR responds to dietary LF supplementation, a mechanism by which LF can promote learning and working memory through its receptor. LfR is expressed in the whole brain, and its expression level is anatomic region specific.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"2857-2871"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Insulin-Like Growth Factor Signaling in Alzheimer's Disease: Pathophysiology and Therapeutic Strategies. 阿尔茨海默病中的胰岛素样生长因子信号传导：病理生理学与治疗策略》。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-06 DOI: 10.1007/s12035-024-04457-1

Jie Miao, Yanli Zhang, Chen Su, Qiandan Zheng, Junhong Guo

{"title":"Insulin-Like Growth Factor Signaling in Alzheimer's Disease: Pathophysiology and Therapeutic Strategies.","authors":"Jie Miao, Yanli Zhang, Chen Su, Qiandan Zheng, Junhong Guo","doi":"10.1007/s12035-024-04457-1","DOIUrl":"10.1007/s12035-024-04457-1","url":null,"abstract":"Alzheimer's disease (AD) is the leading cause of dementia among the elderly population, posing a significant public health challenge due to limited therapeutic options that merely delay cognitive decline. AD is associated with impaired energy metabolism and reduced neurotrophic signaling. The insulin-like growth factor (IGF) signaling pathway, crucial for central nervous system (CNS) development, metabolism, repair, cognition, and emotion regulation, includes IGF-1, IGF-2, IGF-1R, IGF-2R, insulin receptor (IR), and six insulin-like growth factor binding proteins (IGFBPs). Research has identified abnormalities in IGF signaling in individuals with AD and AD models. Dysregulated expression of IGFs, receptors, IGFBPs, and disruptions in downstream phosphoinositide 3-kinase-protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) pathways collectively increase AD susceptibility. Studies suggest modulating the IGF pathway may ameliorate AD pathology and cognitive decline. This review explores the CNS pathophysiology of IGF signaling in AD progression and assesses the potential of targeting the IGF system as a novel therapeutic strategy. Further research is essential to elucidate how aberrant IGF signaling contributes to AD development, understand underlying molecular mechanisms, and evaluate the safety and efficacy of IGF-based treatments.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3195-3225"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Monosome Stalls the Translation Process Mediated by IGF2BP in Arcuate Nucleus for Puberty Onset Delay. 单体阻滞了弓状核中由 IGF2BP 介导的翻译过程，导致青春期发病延迟

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-05 DOI: 10.1007/s12035-024-04450-8

Yifen Shen, Le Zhang, Tao Yang, Xiaosong Li, Chao Liu, Hongmei Li, Yanping Hu, Hao Shen, Hua Li, Yuriy L Orlov, Shasha Zhou, Yihang Shen

{"title":"Monosome Stalls the Translation Process Mediated by IGF2BP in Arcuate Nucleus for Puberty Onset Delay.","authors":"Yifen Shen, Le Zhang, Tao Yang, Xiaosong Li, Chao Liu, Hongmei Li, Yanping Hu, Hao Shen, Hua Li, Yuriy L Orlov, Shasha Zhou, Yihang Shen","doi":"10.1007/s12035-024-04450-8","DOIUrl":"10.1007/s12035-024-04450-8","url":null,"abstract":"Puberty onset through hypothalamic-pituitary-gonad (HPG) axis as an important reproductive event in postnatal development is initiated from hypothalamic arcuate nucleus (ARC). The growing evidence indicates that translational control also plays an essential role in the final expression of gonadotropin genes. To investigate the role of protein translation and behavior of ribosomes in pubertal onset, the global profiles of transcriptome, single ribosome (monosome), polysome, and tandem mass tag proteome were comprehensively investigated in rat hypothalamic ARCs of different pubertal stages using RNA sequencing, polyribo sequencing, and mass spectrum. Transcriptome-wide enrichments of N6-methyladenosine and IGF2BP2 were investigated using meRIP and RIP sequencing. Monosome was robustly enriched on a large proportion of mRNA in early puberty rats (postnatal day (PND)-25) compared to late puberty (PND-35 and PND-45). Monosome-enriched mRNAs, including HPG axis-related genes, had a large number of upstream ORFs (uORF, < 100 nt) and displayed translational repression in early puberty. Furthermore, insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) could particularly interact with and facilitate monosome to bind with mRNA in early puberty. Finally, ectopic over-expression of IGF2BP2 in hypothalamic ARC via lateral ventricle injection in vivo could recruit monosome to aggregate on mRNA and delay puberty onset. We uncovered a novel regulatory mechanism of IGF2BP2 and monosome for translational control in puberty onset, which shed light on the neuroendocrine regulatory network involved in HPG axis activation.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3167-3181"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Mechanism of USP18-Mediated NCOA4 m6A Modification Via Maintaining FTO Stability In Regulating Ferritinophagy-Mediated Ferroptosis in Cerebral Ischemia-Reperfusion Injury. USP18 通过维持 FTO 稳定性介导的 NCOA4 m6A 修饰机制在脑缺血再灌注损伤中调控铁蛋白吞噬作用介导的铁蛋白沉积。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-27 DOI: 10.1007/s12035-024-04494-w

Zongyong Zhang, Zongqing Zheng, Yibiao Chen, Xuegang Niu, Taohui Ouyang, Dengliang Wang

{"title":"Mechanism of USP18-Mediated NCOA4 m6A Modification Via Maintaining FTO Stability In Regulating Ferritinophagy-Mediated Ferroptosis in Cerebral Ischemia-Reperfusion Injury.","authors":"Zongyong Zhang, Zongqing Zheng, Yibiao Chen, Xuegang Niu, Taohui Ouyang, Dengliang Wang","doi":"10.1007/s12035-024-04494-w","DOIUrl":"10.1007/s12035-024-04494-w","url":null,"abstract":"This study aimed to explore whether USP18 regulates cerebral ischemia-reperfusion (I/R) injury via fat mass and obesity-associated proteins (FTO)-mediated NCOA4. Middle cerebral artery occlusion (MCAO) models were established in mice, and PC-12 cells treated with oxygen-glucose deprivation and reperfusion (OGD/R) were used as in vitro models. The USP18 lentiviral vector was transfected into cells in vitro and MCAO mice to observe its effect on ferroptosis. The relationship between USP18 and FTO was assessed using Co-IP and western blot. The effect of FTO on NCOA4 m6A modification was also elucidated. Overexpression of USP18 in MCAO models decreased cerebral infarct size and attenuated pathological conditions in mouse brain tissues. Moreover, USP18 reduced iron content, MDA, ROS, and LDH release, increased GSH levels and cell viability in both MCAO models and OGD/R cells, and promoted LC3 expression and autophagy flux. In vitro experiments on neurons showed that USP18 maintained FTO stability. The presence of FTO-m6A-YTFDH1-NCOA4 was also verified in neurons. Both in vivo and in vitro experiments showed that FTO and NCOA4 abrogated the protective effects of USP18 against ferritinophagy-mediated ferroptosis. Notably, USP18 maintains FTO stability, contributing to the removal of NCOA4 m6A modification and the suppression of NCOA4 translation, which consequently inhibits ferritinophagy-mediated ferroptosis to attenuate cerebral I/R injury.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3848-3862"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Platinum Deposition in the Central Nervous System: A Novel Insight into Oxaliplatin-induced Peripheral Neuropathy in Young and Old Mice. 中枢神经系统中的铂沉积：奥沙利铂诱发年轻和年老小鼠周围神经病变的新视角

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-25 DOI: 10.1007/s12035-024-04430-y

Angélica S Reis, Jaini J Paltian, William B Domingues, Diogo L R Novo, Eduardo Bolea-Fernandez, Thibaut Van Acker, Vinicius F Campos, Cristiane Luchese, Frank Vanhaecke, Marcia F Mesko, Ethel A Wilhelm

{"title":"Platinum Deposition in the Central Nervous System: A Novel Insight into Oxaliplatin-induced Peripheral Neuropathy in Young and Old Mice.","authors":"Angélica S Reis, Jaini J Paltian, William B Domingues, Diogo L R Novo, Eduardo Bolea-Fernandez, Thibaut Van Acker, Vinicius F Campos, Cristiane Luchese, Frank Vanhaecke, Marcia F Mesko, Ethel A Wilhelm","doi":"10.1007/s12035-024-04430-y","DOIUrl":"10.1007/s12035-024-04430-y","url":null,"abstract":"Numerous factors can contribute to the incidence or exacerbation of peripheral neuropathy induced by oxaliplatin (OXA). Recently, platinum accumulation in the spinal cord of mice after OXA exposure, despite the efficient defenses of the central nervous system, has been demonstrated by our research group, expanding the knowledge about its toxicity. One hypothesis is platinum accumulation in the spinal cord causes oxidative damage to neurons and impairs mitochondrial function. Thus, the main aim of this study was to investigate the relationship between aging and OXA-induced neuropathic pain and its comorbidities, including anxious behavior and cognitive impairment. By using an OXA-induced peripheral neuropathy model, platinum and bioelement concentrations and their influence on oxidative damage, neuroprotection, and neuroplasticity pathways were evaluated in Swiss mice, and our findings showed that treatment with OXA exacerbated pain and anxious behavior, albeit not age-induced cognitive impairment. Platinum deposition in the spinal cord and, for the first time, in the brain of mice exposed to OXA, regardless of age, was identified. We found that alterations in bioelement concentration, oxidative damage, neuroprotection, and neuroplasticity pathways induced by aging contribute to OXA-induced peripheral neuropathy. Our results strive to supply a basis for therapeutic interventions for OXA-induced peripheral neuropathy considering age specificities.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3712-3729"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Spinal PTP1B Regulated NMDA Receptor-mediated Nociceptive Transmission and Peripheral Inflammation-induced Pain Sensitization. 脊髓PTP1B调控NMDA受体介导的痛觉传导和外周炎症诱导的痛觉敏感化

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-26 DOI: 10.1007/s12035-024-04519-4

Shu-Jin Wu, Xin-Yi Lan, Yue Shi, Yan-Ni Liu, Xiao-Xi Zhang, Qi Zhang, Yu-Bo Gao, Juan Li, Xian Yang, Hu-Hu Bai

{"title":"Spinal PTP1B Regulated NMDA Receptor-mediated Nociceptive Transmission and Peripheral Inflammation-induced Pain Sensitization.","authors":"Shu-Jin Wu, Xin-Yi Lan, Yue Shi, Yan-Ni Liu, Xiao-Xi Zhang, Qi Zhang, Yu-Bo Gao, Juan Li, Xian Yang, Hu-Hu Bai","doi":"10.1007/s12035-024-04519-4","DOIUrl":"10.1007/s12035-024-04519-4","url":null,"abstract":"Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of several pain-related substrates in spinal cord dorsal horn and are critically involved in the modification of pain transmission. The current study demonstrated that protein tyrosine phosphatase 1B (PTP1B), a unique endoplasmic reticulum-resident member of PTP family, displayed an activity-dependent increase in its protein expression and synaptic localization in spinal dorsal horn of adult male rats. PTP1B interacted with the Src Homology 3 (SH3) domain of Synapse-Associated Protein 102 (SAP102), one of the postsynaptic scaffolding proteins that anchored PTP1B at postsynaptic sites. The SAP102-tethered PTP1B augmented the synaptic transmission mediated specifically by GluN2B subunit-containing N-methyl-D-aspartate subtype glutamate receptors. Interference with PTP1B activity or disruption of its interaction with SAP102 attenuated GluN2B-mediated nociceptive transmission and ameliorated pain sensitization induced by intraplantar injection of Complete Freund's Adjuvant. These data suggested that the activity-dependent synaptic redistribution of PTP1B served as an important mechanism regulating GluN2B receptor activity and that manipulation of PTP1B synaptic targeting might represent an effective approach for the treatment of chronic inflammatory pain.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3781-3793"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The Multifaceted Role of L-Type Amino Acid Transporter 1 at the Blood-Brain Barrier: Structural Implications and Therapeutic Potential. L 型氨基酸转运体 1 在血脑屏障中的多方面作用：结构意义与治疗潜力

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-26 DOI: 10.1007/s12035-024-04506-9

H Shafeeq Ahmed

{"title":"The Multifaceted Role of L-Type Amino Acid Transporter 1 at the Blood-Brain Barrier: Structural Implications and Therapeutic Potential.","authors":"H Shafeeq Ahmed","doi":"10.1007/s12035-024-04506-9","DOIUrl":"10.1007/s12035-024-04506-9","url":null,"abstract":"L-type amino acid transporter 1 (LAT1) is integral to the transport of large neutral amino acids across the blood-brain barrier (BBB), playing a crucial role in brain homeostasis and the delivery of therapeutic agents. This review explores the multifaceted role of LAT1 in neurological disorders, including its structural and functional aspects at the BBB. Studies using advanced BBB models, such as induced pluripotent stem cell (iPSC)-derived systems and quantitative proteomic analyses, have demonstrated LAT1's significant impact on drug permeability and transport efficiency. In Alzheimer's disease, LAT1-mediated delivery of anti-inflammatory and neuroprotective agents shows promise in overcoming BBB limitations. In Parkinson's disease, LAT1's role in transporting L-DOPA and other therapeutic agents highlights its potential in enhancing treatment efficacy. In phenylketonuria, studies have revealed polymorphisms and genetic variations of LAT1, which could be correlated to disease severity. Prodrugs of valproic acid, pregabalin, and gabapentin help use LAT1-mediated transport to increase the therapeutic activity and bioavailability of the prodrug in the brain. LAT1 has also been studied in neurodevelopment disorders like autism spectrum disorders and Rett syndrome, along with neuropsychiatric implications in depression. Its implications in neuro-oncology, especially in transporting therapeutic agents into cancer cells, show immense future potential. Phenotypes of LAT1 have also shown variations in the general population affecting their ability to respond to painkillers and anti-inflammatory drugs. Furthermore, LAT1-targeted approaches, such as functionalized nanoparticles and prodrugs, show promise in overcoming chemoresistance and enhancing drug delivery to the brain. The ongoing exploration of LAT1's structural characteristics and therapeutic applications reiterates its critical role in advancing treatments for neurological disorders.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3813-3832"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Tetrameric Transthyretin as a Protective Factor Against Alzheimer's Disease. 作为阿尔茨海默病保护因子的四聚体转甲状腺素

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-08-27 DOI: 10.1007/s12035-024-04442-8

Camilla Corino, Alberto Aimo, Marco Luigetti, Lidia Ciccone, Yu Fu Ferrari Chen, Giorgia Panichella, Veronica Musetti, Vincenzo Castiglione, Giuseppe Vergaro, Michele Emdin, Maria Franzini

{"title":"Tetrameric Transthyretin as a Protective Factor Against Alzheimer's Disease.","authors":"Camilla Corino, Alberto Aimo, Marco Luigetti, Lidia Ciccone, Yu Fu Ferrari Chen, Giorgia Panichella, Veronica Musetti, Vincenzo Castiglione, Giuseppe Vergaro, Michele Emdin, Maria Franzini","doi":"10.1007/s12035-024-04442-8","DOIUrl":"10.1007/s12035-024-04442-8","url":null,"abstract":"Transthyretin (TTR) is a tetrameric protein traditionally recognized for its role in transporting thyroxine and retinol. Recent research has highlighted the potential neuroprotective functions of TTR in the setting of Alzheimer's disease (AD), which is the most common form of dementia and is caused by the deposition of amyloid beta (Aβ) and the resulting cytotoxic effects. This paper explores the mechanisms of TTR protective action, including its interaction with Aβ to prevent fibril formation and promote Aβ clearance from the brain. It also synthesizes experimental evidence suggesting that enhanced TTR stability may mitigate neurodegeneration and cognitive decline in AD. Potential therapeutic strategies such as small molecule stabilizers of TTR are discussed, highlighting their role in enhancing TTR binding to Aβ and facilitating its clearance. By consolidating current knowledge and proposing directions for future research, this review aims to underscore the significance of TTR as a neuroprotective factor in AD and the potential implications for future research.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"2945-2954"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

TRPV4 Channel in Neurological Disease: from Molecular Mechanisms to Therapeutic Potential. 神经系统疾病中的 TRPV4 通道：从分子机制到治疗潜力。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-28 DOI: 10.1007/s12035-024-04518-5

Feng Zhang, Hritik Mehta, Hadi Hasan Choudhary, Rezwanul Islam, Khalid A Hanafy

{"title":"TRPV4 Channel in Neurological Disease: from Molecular Mechanisms to Therapeutic Potential.","authors":"Feng Zhang, Hritik Mehta, Hadi Hasan Choudhary, Rezwanul Islam, Khalid A Hanafy","doi":"10.1007/s12035-024-04518-5","DOIUrl":"10.1007/s12035-024-04518-5","url":null,"abstract":"Transient Receptor Potential Vanilloid 4 (TRPV4) is a non-selective cation channel with pivotal roles in various physiological processes, including osmosensitivity, mechanosensation, neuronal development, vascular tone regulation, and bone homeostasis in human bodies. Recent studies have made significant progress in understanding the structure and functional role of TRPV4, shedding light on its involvement in pathological processes, particularly in the realm of neurological diseases. Here, we aim to provide a comprehensive exploration of the multifaceted contributions of TRPV4 to neurological diseases, spanning its intricate molecular mechanisms to its potential as a target for therapeutic interventions. We delve into the structural and functional attributes of TRPV4, scrutinize its expression profile, and elucidate the possible mechanisms through which it participates in the pathogenesis of neurological disorders. Furthermore, we discussed recent years' progress in therapeutic strategies aimed at harnessing TRPV4 for the treatment of these diseases. These insights will provide a basis for understanding and designing modality-specific pharmacological agents to treat TRPV4-associated disorders.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3877-3891"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Specific Activation of Dopamine Receptor D1 Expressing Neurons in the PrL Alleviates CSDS-Induced Anxiety-Like Behavior Comorbidity with Postoperative Hyperalgesia in Male Mice. 特异性激活 PrL 中表达多巴胺受体 D1 的神经元可缓解 CSDS 诱导的雄性小鼠焦虑样行为与术后过痛的并发症。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-08-23 DOI: 10.1007/s12035-024-04444-6

Wang Wang, Weizhen Liu, Sufang Liu, Dongxiao Duan, Yajing Ma, Zijuan Zhang, Changsheng Li, Yuanyuan Tang, Zhiju Wang, Ying Xing

{"title":"Specific Activation of Dopamine Receptor D1 Expressing Neurons in the PrL Alleviates CSDS-Induced Anxiety-Like Behavior Comorbidity with Postoperative Hyperalgesia in Male Mice.","authors":"Wang Wang, Weizhen Liu, Sufang Liu, Dongxiao Duan, Yajing Ma, Zijuan Zhang, Changsheng Li, Yuanyuan Tang, Zhiju Wang, Ying Xing","doi":"10.1007/s12035-024-04444-6","DOIUrl":"10.1007/s12035-024-04444-6","url":null,"abstract":"Postoperative pain is a type of pain that occurs in clinical patients after surgery. Among the factors influencing the transition from acute postoperative pain to chronic postoperative pain, chronic stress has received much attention in recent years. Here, we investigated the role of dopamine receptor D1/D2 expressing pyramidal neurons in the prelimbic cortex (PrL) in modulating chronic social defeat stress (CSDS)-induced anxiety-like behavior comorbidity with postoperative hyperalgesia in male mice. Our results showed that preoperative CSDS induced anxiety-like behavior and significantly prolonged postoperative pain caused by plantar incision, but did not affect plantar wound recovery and inflammation. Reduced activation of dopamine receptor D1 or D2 expressing neurons in the PrL is a remarkable feature of male mice after CSDS, and chronic inhibition of dopamine receptor D1 or D2 expressing neurons in the PrL induced anxiety-like behavior and persistent postoperative pain. Further studies found that activation of D1 expressing but not D2 expressing neurons in the PrL ameliorated CSDS-induced anxiety-like behavior and postoperative hyperalgesia. Our results suggest that dopamine receptor D1 expressing neurons in the PrL play a crucial role in CSDS-induced anxiety-like behavior comorbidity with postoperative hyperalgesia in male mice.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"2817-2834"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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