Neurochemical Research最新文献

{"title":"A Pharmacological Perspective on Targeting the Voltage-Gated Calcium Channel Subunit α2δ(1–2) to Mitigate Traumatic Brain Injury Sequelae","authors":"Jijo Stebin Justus,&nbsp;Marcelo S. Rodolphi,&nbsp;Bruna Valdameri,&nbsp;Vitória G. de Oliveira,&nbsp;Nathan R. Strogulski,&nbsp;Marco A. Stefani,&nbsp;Luis V. Portela","doi":"10.1007/s11064-025-04565-x","DOIUrl":"10.1007/s11064-025-04565-x","url":null,"abstract":"<div><p>Traumatic brain injury (TBI) is a significant global public health issue, affecting millions annually. Excessive calcium influx in neurons and astrocytes triggers a cascade of neurotoxic events, including mitochondrial dysfunction, increased production of reactive oxygen species, and hypometabolism, all of which contribute to impaired neurological function. Following TBI, alterations in presynaptic voltage-gated calcium channels (VGCCs) and the formation of plasma membrane pores facilitate Ca²⁺ influx, membrane depolarization, and an increased vesicular release of glutamate and Ca²⁺ into the synaptic cleft. This leads to the overactivation of NMDA receptors and the propagation of neurotoxic Ca²⁺ signals to neighboring neurons, further spreading neurobiochemical disruptions. Given this, blocking Ca²⁺ influx may mitigate excitotoxicity, and mitochondrial alterations caused by TBI. Among the pathways involved in Ca²⁺ cytotoxicity, the alpha-2-delta (α₂δ_(1–2)) subunit of VGCCs, located at the presynaptic terminal, remains the least explored. In this review, we briefly examine the pathophysiological hallmarks of TBI and their connection to Ca²⁺ dysregulation, while exploring the distribution of VGCC subtypes in the brain. Additionally, we highlight pregabalin, an analog of gabapentin and a selective antagonist of the α₂δ_(1–2) subunit, as a promising therapeutic strategy to counteract Ca²⁺-induced neurotoxicity following TBI.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145012","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}

{"title":"Banxia Shumi Decoction Improves Sleep and Neural Function in Insomnia Male Rats via BDNF/TrkB/CREB-Dependent Melatonin Signaling Activation","authors":"Baojun Guo,&nbsp;Yuqin Tang,&nbsp;Yunjuan Wang,&nbsp;Qian Ma,&nbsp;Ying Wang,&nbsp;Yongqiang Zhang,&nbsp;Ranran Gao","doi":"10.1007/s11064-025-04556-y","DOIUrl":"10.1007/s11064-025-04556-y","url":null,"abstract":"<div><p>Insomnia seriously affects people’s quality of life and health. Currently available insomnia medications demonstrate notable side effect profiles and lack well-established evidence regarding their sustained efficacy. The aim of this study was to investigate the efficacy of Banxia Shumi decoction (BXSMD) in insomnia and the molecular mechanism involved. The effect of BDNF/TrkB/CREB pathway on BSXMD treatment of insomnia was investigated by using p-chlorophenylalanine (PCPA) induced insomnia male rat model. The results of open field test, Morris water maze and hypnosis experiments implied that circadian dysrhythmia, increased open-field activity, decreased sleep quality and learning and memory impairments were observed in insomnia male rat. Besides, the levels of BDNF/TrkB/CREB pathway, 5-HT, MT, MT1 and MT2 were reduced, accompanied with neural tissue damage in insomnia male rats by ELISA, qRT-PCR, WB, immunohistochemistry and HE staining. BXSMD alleviated neural tissue damage and improved sleep quality along with cognitive functions (learning and memory) in insomnia male rats. Moreover, BXSMD caused activation of BDNF/TrkB/CREB pathway and upregulation of 5-HT, MT, MT1 and MT2 levels in insomnia male rats. BDNF overexpression-mediated activation of BDNF/TrkB/CREB pathway enhanced the pharmacological effects of BXSMD described above. Notably, MT1/MT2 antagonist attenuated the therapeutic effects of BXSMD on sleep disturbances and neural tissue damage in insomnia male rats, while BDNF knockdown in the hippocampus suppressed BXSMD-mediated activation of MT signaling, sleep enhancement, and neuroprotection. In summary, this study elucidated that BXSMD enhanced MT signaling by activating BDNF/TrkB/CREB pathway in the hippocampus, thereby ameliorating sleep disorders and neural damage in insomnia male rats.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129683","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}

{"title":"Neuroinflammation in an Optimized Model of Lysophosphatidic Acid (LPA)-Induced Post-hemorrhagic Hydrocephalus","authors":"Paloma Sánchez-Pavón,&nbsp;Carter R. Palmer,&nbsp;Christine S. Liu,&nbsp;Valerie P. Tan,&nbsp;Victoria A. Blaho,&nbsp;Jerold Chun","doi":"10.1007/s11064-025-04542-4","DOIUrl":"10.1007/s11064-025-04542-4","url":null,"abstract":"<div><p>Post-hemorrhagic hydrocephalus (PHH) is a neurological disease that primarily affects premature infants and involves infiltration of blood into the brain’s ventricles followed by excessive accumulation of cerebrospinal fluid (CSF), leading to ventricular enlargement and increased intracranial pressure. The precise mechanisms driving PHH development and persistence are incompletely understood and lack disease-modifying treatments. Using a mouse model of PHH, we have identified transcriptomic, proteomic, and cellular features of PHH involving neuroimmune and neurovascular alterations recapitulating those reported in human disease. Improvement upon a lysophosphatidic acid (LPA)-induced PHH mouse model was combined with unbiased proteomic and single-nucleus transcriptomics that identified microglial molecular pathways propagating PHH. Pharmacological depletion of microglia in vivo significantly reduced PHH-associated ventriculomegaly. These data identify microglial and neurovascular elements in the development of PHH, implicating them as other potentially tractable therapeutic targets beyond LPA receptors, towards developing medical treatments for PHH.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04542-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078827","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}

{"title":"Induced Overexpression of Connexin43 in Astrocytes Attenuates the Progression of Experimental Temporal Lobe Epilepsy","authors":"Oussama Kherbouche,&nbsp;Lukas Henning,&nbsp;Pia Niemann,&nbsp;Caroline Geisen,&nbsp;Gerald Seifert,&nbsp;Christian Henneberger,&nbsp;Bernd K. Fleischmann,&nbsp;Christian Steinhäuser,&nbsp;Peter Bedner","doi":"10.1007/s11064-025-04558-w","DOIUrl":"10.1007/s11064-025-04558-w","url":null,"abstract":"<div><p>Astrocytic gap junctional communication plays a critical role in regulating neuronal activity and network synchronization, yet its precise contributions to brain function and the pathogenesis of neurological disorders remains incompletely understood. To address this, we generated a transgenic mouse line with inducible, astrocyte-specific overexpression of the gap junction protein connexin43 (Cx43). In these mice, hippocampal astrocytes exhibited markedly elevated Cx43 protein levels and a ~ 20% increase in intercellular gap junction coupling. Enhanced coupling was accompanied by a reduction in astrocytic cell volume and branching, without affecting passive membrane properties or astrocyte density in the hippocampus. Cx43 overexpression had no detectable impact on adult neurogenesis in the dentate gyrus, nor did it alter hippocampal synaptic efficacy or plasticity. Notably, in a mouse model of temporal lobe epilepsy with hippocampal sclerosis, astrocytic Cx43 overexpression attenuated chronic epileptic activity and the extent of sclerosis, supporting an antiepileptic role of the astroglial network. Collectively, these findings enhance our understanding of the functional relevance of astrocytic gap junction coupling in health and disease, with potential implications for the design of new treatment strategies.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-025-04558-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073924","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}

{"title":"Stigmasterol Alleviates Levodopa-Induced Dyskinesia in 6-OHDA-Induced Parkinsonian Rats","authors":"Mayuri Wankhede,&nbsp;Ketan Rathod,&nbsp;Manoj Aswar,&nbsp;Urmila Aswar","doi":"10.1007/s11064-025-04555-z","DOIUrl":"10.1007/s11064-025-04555-z","url":null,"abstract":"<div><p>Chronic treatment with levodopa often leads to levodopa-induced dyskinesia (LID), around 40% of individuals are affected. Stigmasterol exhibits antioxidant, anti-inflammatory, and glutamate-antagonist properties, acting through AKT-1, VEGFR, and IL-6 to prevent neuronal death. This study investigates the STI potential to mitigate LID. Male Sprague Dawley rats were assigned to five groups (SHAM, 6-OHDA, LID, STI 10, STI 20), with <i>n</i> = 10. PD was induced by stereotaxic infusion of 6-OHDA (3 µg/µL × 2.5 µL) into the right medial forebrain bundle. After a 21-day recovery period, development of PD was confirmed through behavioral assessment, including APO-induced rotation, footprint analyses, and a stepping test assessment conducted over 7 days. Subsequently, the rats were treated with levodopa + carbidopa and stigmasterol (10/20 mg/Kg) orally for 28 days. Abnormal involuntary movements (AIMs) were assessed at intervals of 1, 14, 21, and 28th days to evaluate the effect of stigmasterol on LID. On day 28, rats were euthanized, and brain samples were analyzed for biochemical, and histopathological changes in the striatum and substantia nigra using nissl staining. STI treatment (10/20 mg/Kg) significantly decreased AIMS, MDA level, TNF-α, IL-1β, NF- kB, and NLRP3 and significantly increased GSH, SOD, catalase and dopamine levels. The histopathology assessment restored neurons in the striatum and substantia nigra of the brain. The result concludes that co-administration of stigmasterol (10/20 mg/Kg) with L-DOPA + carbidopa restores DA level, showing anti-inflammatory, anti-oxidant properties, and neuroprotective activity. Stigmasterol can therefore be administered as an adjuvant treatment to delay LID.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073925","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}

{"title":"Sinomenine Modifies Parkinson’s Disease Through Nrf2 Activation","authors":"Lingling Zhu,&nbsp;Lin Lin,&nbsp;Zhenyu Yang,&nbsp;Hongxia Tang,&nbsp;Jinping Wu,&nbsp;Zeyi Kang,&nbsp;Yi Feng,&nbsp;Binbin Zheng,&nbsp;Qirou Hu,&nbsp;Shanshan Wang,&nbsp;Cuimin Liu,&nbsp;Zhengli Jiang,&nbsp;Suzhi Liu,&nbsp;Gang Wu","doi":"10.1007/s11064-025-04557-x","DOIUrl":"10.1007/s11064-025-04557-x","url":null,"abstract":"<div><h3>Background</h3><p>Disease-modifying treatments for Parkinson’s disease (PD) are urgently needed, with the Nrf2/ARE pathway a promising target. This study aims to explore the effects of sinomenine on PD and Nrf2/ARE activation.</p><h3>Methods</h3><p>6-OHDA-treated Parkinsonian SH-SY5Y cells and rats were used. Apoptosis and cell viability were measured using flow cytometry and CCK-8 assays. Nrf2 and its downstream proteins were assessed by Western blotting, while ROS levels were detected with fluorescent dyes. Nrf2 silencing via shRNA evaluated sinomenine’s dependence on Nrf2 activation. In vivo, behavioral changes, tyrosine hydroxylase (TH) levels and malondialdehyde (MDA) levels were measured. Microglial inflammation was analyzed by measuring TNF-α and IL-1β expression and cytoskeleton analysis. Nrf2 nuclear translocation was verified by Western blotting and molecular docking was performed.</p><h3>Results</h3><p>Sinomenine reduced apoptosis and ROS, improved cell viability, upregulated Nrf2 and antioxidant enzyme expression. The protective effects against apoptosis were abolished by Nrf2 silencing. In PD animals, sinomenine improved motor deficits, enhanced Nrf2, GCLC, GCLM, NQO1, and HO-1 expression, decreased MDA levels, increased TH levels in the striatum and maintained count of dopaminergic neurons in substantia nigra. Additionally, it suppressed TNF-α and IL-1β levels in brain tissue and blood, preserving normal microglial morphology and reducing neuroinflammation. Sinomenine promoted Nrf2 nuclear translocation and showed high Keap1 affinity in docking.</p><h3>Conclusions</h3><p>Sinomenine activates the Nrf2/ARE pathway, mitigating oxidative stress and inflammation in PD models, possibly through Keap1 binding and Nrf2 nuclear translocation. These findings suggest sinomenine may serve as a potential disease-modifying therapy for Parkinson’s disease, pending further clinical validation.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073926","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}

{"title":"Special Collection of Neurochemical Research Volume 50, 2025 in Remembrance of Prof. Arne Schousboe","authors":"Arne Schousboe,&nbsp;Henry Sershen","doi":"10.1007/s11064-025-04526-4","DOIUrl":"10.1007/s11064-025-04526-4","url":null,"abstract":"","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037229","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}

{"title":"Riboflavin (Vitamin B2) Accumulation Modulates Neuronal Cellular Homeostasis in Typical Brain Development and Cerebral Palsy","authors":"Eulália Rebeca Silva-Araújo,&nbsp;Eduardo Padrón-Hernández,&nbsp;Ana Elisa Toscano,&nbsp;Osmar Henrique dos Santos Júnior,&nbsp;Joaci Pereira dos Santos Júnior,&nbsp;Henrique José Cavalcanti Bezerra Gouveia,&nbsp;Adriana Soares de Carvalho,&nbsp;Janaína Viana de Melo,&nbsp;Luiz Alberto Reis Mattos-Júnior,&nbsp;Raul Manhães-de-Castro","doi":"10.1007/s11064-025-04552-2","DOIUrl":"10.1007/s11064-025-04552-2","url":null,"abstract":"<div><p>The developing brain requires high energy demands and metabolic efforts to regulate oxidative stress and myelination. Early insults cause mitochondrial dysfunction and compromise these pathways, potentially leading to cerebral palsy (CP), a severe and incurable neurological disorder that begins in childhood. Through a rodent preclinical study, we demonstrated that vitamin B2 (riboflavin), administered at a high dose (100 mg/kg), is accumulated in healthy (B2C) or paralytic (B2CP) brains and participates in neurodevelopment. Redox homeostasis was maintained in B2C through decreased malondialdehyde and carbonyls and increased glutathione-S-transferase activity. In B2CP rodents, there was a reduction in carbonyls and increased superoxide dismutase activity. Mitochondrial morphometric analysis suggests that riboflavin treatment increases biogenesis in controls and reduces mitochondrial deformation in CP. Ultrastructural analysis revealed increased myelin sheath thickness in B2C. Additionally, myelin figure formation and mitochondrial and axonal disintegration in CP were reduced by B2. Our evidence supports vitamin B2 accumulation as a beneficial mechanism to support energy homeostasis and mitochondrial demands that occur during typical neurodevelopment or in the face of CP.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037227","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}

{"title":"Methylsulfonylmethane Mitigates Neurobehavioral Impairment, Oxidative Stress, Changes in Trace Elements and Clock Expression in Alcohol and Circadian-Disrupted C57BL/6J Mice Brain","authors":"Indrani Paramasivan Latha Laxmi,&nbsp;Ramasamy Tamizhselvi","doi":"10.1007/s11064-025-04551-3","DOIUrl":"10.1007/s11064-025-04551-3","url":null,"abstract":"<div><p>Alcohol consumption can affect the brain due to an elevation in oxidative stress and inflammation. Alcoholism influences the brain homeostasis and is often associated with cognitive, emotional and behavioral changes. Excessive alcohol intake can lead to poor sleep quality, and individuals with alcohol use disorder generally develop insomnia. Alcohol use affects the expression of clock genes, altering the physiological and immune function regulated by the biological clock, and hence elevating the production of reactive oxygen species. This study aimed to explore the alterations in neurobehavioral function associated with circadian disturbance and alcohol exposure, and to understand the potential therapeutic effect of methylsulfonylmethane on alcohol-administered and circadian-disrupted C57BL/6J mice. The sleep cycle of the mice was disturbed by 10 h light/10 h dark exposure, and 25% w/v alcohol was administered to the mice intragastrically. The concentration of trace elements in the mouse brain was measured using Inductively Coupled Mass Spectrometry (ICP-MS). An increase in anxiety-like behavior was observed in the mice exposed to alcohol and the circadian-disrupted groups. The administration of the drug significantly increased the expression of core clock genes in the alcohol and circadian-disrupted group. The levels of calcium and iron were increased in the MSM-administered mice, reversing the effects of circadian disruption and the alcohol-exposed group of mice. Our findings suggest that alcohol and circadian disturbance impact neurological function through alterations in immune homeostasis. MSM treatment can improve the expression of clock genes in alcohol and circadian-disrupted conditions, highlighting its neuroprotective potential by reducing inflammation.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037228","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}

{"title":"Cholesterol-Lowering Treatment Suppresses Neuromuscular Transmission Via Presynaptic Mechanism at the Mouse Diaphragm Muscle","authors":"Guzel F. Zakyrjanova,&nbsp;Andrei N. Tsentsevitsky,&nbsp;Valeriya A. Matigorova,&nbsp;Nikita S. Fedorov,&nbsp;Julia G. Odnoshivkina,&nbsp;Guzel V. Sibgatullina,&nbsp;Eva A. Kapliukhina,&nbsp;Arthur R. Giniatullin,&nbsp;Arthur N. Khaziev,&nbsp;Artem I. Malomouzh,&nbsp;Yuri V. Gogolev,&nbsp;Alexey M Petrov","doi":"10.1007/s11064-025-04550-4","DOIUrl":"10.1007/s11064-025-04550-4","url":null,"abstract":"<div><p>Statins are widely prescribed and effective cholesterol-lowering drugs for the therapy of cerebrovascular and cardiovascular disorders. The main side effects limiting statin use are muscle-related adverse events, including weakness and myopathy. The precise mechanisms of statin-induced muscle damage remain to be elucidated. Possible alterations in neuromuscular transmission might contribute to the statin side effects. Here, we studied the action of one-month treatment with atorvastatin, the most prescribed statin, on the functioning of neuromuscular junctions and related processes in the mouse diaphragm. We found that atorvastatin treatment decreases evoked acetylcholine (ACh) release and involvement of synaptic vesicles in exocytosis during intense nerve activation, as well as recovery of ACh release after tetanic stimulation. This was accompanied by increased immunolabeling of synapsin 1, a protein retaining synaptic vesicles in a non-active pool, and decreased non-quantal ACh release under resting conditions. Additionally, atorvastatin administration decreased perimeters of postsynaptic ACh receptor clusters without signs of muscle denervation. Diaphragm contractile responses to phrenic nerve stimulation at moderate-to-high frequencies and peak inspiratory flow, an indicator of diaphragm function in vivo, were decreased in atorvastatin-treated mice, whereas diaphragm contractions elicited by direct stimulation of muscle fibers were unchanged. Thus, atorvastatin treatment caused a decline in evoked ACh release and synaptic vesicle recruitment into neurotransmission that could lead to a reduction of diaphragm contractile responses to phrenic nerve activity and peak inspiratory flow. These alterations, in combination with decreased non-quantal ACh release and neuromuscular junction size, may contribute to statin-associated muscle symptoms.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028412","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}