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Biochemical dissection of STAT3 signaling in amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第11期20卷 3229-3230页

作者： Savina Apolloni Nadia d’Ambrosi department of Biology University of Rome Tor VergataRomeItaly

Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons,clinically marked by muscle atrophy and *** the clinical course is highly variable,the average time from the onset of symptoms to the need for respiratory support or death is 3-5 *** is the most prevalent motor neuron disease in adults,occurring at a rate of 2 per 100,000 individuals and affecting 5.4 per 100,000 individuals overall.

关键词： STAT3 dissection sclerosis

Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

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Neural Regeneration Research 2025年第4期20卷 1092-1093页

作者： danko Jeremic Lydia Jiménez-díaz Juan d.Navarro-López NeuroPhysiology&Behavior Lab University of Castilla-La ManchaBiomedical Research Center(CRIB)School of Medicine of Ciudad RealCiudad RealSpain

Although many causes of Alzheimer’s disease(Ad)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the ***,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in Ad,being able to precede and influence one *** researchers argue that these proteins are mere executors rather than primary causes of ***,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early ***,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).

关键词： amyloid Alzheimer additive

Remaking a connection:molecular players involved in post-injury synapse formation

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Neural Regeneration Research 2025年第6期20卷 1719-1720页

作者： diogo Tomé Ramiro d.Almeida iBimEd-Institute of Biomedicine Department of Medical SciencesUniversity of AveiroAveiroPortugal CNC-Center for Neuroscience and Cell Biology University of CoimbraCoimbraPortugal

Functional recovery from central nervous system(CNS)trauma depends not only on axon regeneration or compensatory sprouting of uninjured fibers but also on the ability of newly grown axons to establish functional synapses with appropriate *** several studies have successfully promoted long-distance axonal regeneration in distinct CNS injury models,none of them have resulted in a viable therapeutic approach for patient recovery.A possible reason may be the lack of new synaptogenesis for reestablishing the circuitry lost after ***,we discuss how our understanding of the mechanisms that instruct synapse formation in the injured nervous system may contribute to the design of new strategies to promote functional restoration in traumatic CNS disorders.

关键词： viable injury instru

Nonlinear forced vibration in a subcritical regime of a porous functionally graded pipe conveying fluid with a retaining clip

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Applied mathematics and mechanics(English Edition) 2025年第1期46卷 101-122页

作者： m.GHOLAmI m.EFTEKHARI department of mechanical Engineering Shahid Bahonar University of Kerman

This study examines the nonlinear behaviors of a clamped-clamped porous pipe made of a functionally graded material(FGm) that conveys fluids and is equipped with a retaining clip, focusing on primary resonance and subcritical dynamics. The nonlinear governing equations for the FGm pipe are derived by the extended Hamilton's principle, and subsequently discretized through the application of the Galerkin *** direct method of multi-scales is then used to solve the derived equations. A thorough analysis of various parameters, including the clip stiffness, the power-law index, the porosity, and the clip location, is conducted to gain a comprehensive understanding of the system's nonlinear dynamics. Through the analysis of the first natural frequency, the study highlights the influence of the flow velocity and the clip stiffness, while the comparisons with metallic pipes emphasize the role of FGm composition. The examination of the forced response curves reveals saddle-node bifurcations and their dependence on parameters such as the detuning parameter and the power-law index, offering valuable insights into the system's nonlinear resonant behavior. Furthermore, the frequency-response curves illustrate the hardening nonlinearities influenced by factors such as the porosity and the clip stiffness, revealing nuanced effects on the system response and resonance characteristics. This comprehensive analysis enhances the understanding of nonlinear behaviors in FGm porous pipes with a retaining clip, providing key insights for practical engineering applications in system design and optimization.

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The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： Jennifer m.Colón-mercado Aranza I.Torrado-Tapias Iris K.Salgado Jose m.Santiago Samuel E.Ocasio Rivera dina P.Bracho-Rincon Luis H.Pagan Rivera Jorge d.miranda department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA National Institutes of Health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto Rico Carolina CampusCarolinaPRUSA Institute of Neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

Neurogenesis dynamics in the olfactory bulb:deciphering circuitry organization, function, and adaptive plasticity

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Neural Regeneration Research 2025年第6期20卷 1565-1581页

作者： moawiah m.Naffaa department of Psychology and Neuroscience Duke UniversityDurhamNCUSA department of Cell Biology Duke University School of MedicineDurhamNCUSA

Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased

关键词： network adaptability neurogenesis neuronal communication olfactory bulb olfactory learning olfactory memory synaptic plasticity

Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of Parkinson’s disease

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Neural Regeneration Research 2025年第2期20卷 574-586页

作者： Olivier Kerdiles méryl-Farelle Oye mintsa mi-mba Katherine Coulombe Cyntia Tremblay VincentÉmond martine Saint-Pierre Clémence Rouxel Line Berthiaume Pierre Julien Francesca Cicchetti Frédéric Calon Facultéde pharmacie UniversitéLaval1050 Avenue de la MédecineQuebecQCCanada Axe Neuroscience Centre de recherche du CHU de Québec-UniversitéLaval(Pavillon CHUL)2705 Boulevard LaurierQuebecQCCanada Institute of Nutrition and Functional Foods QuebecQCCanada Optinutribrain International Associated Laboratory(NutriNeuro FranceINAFCanada)QuebecQCCanada Axe Endocrinologie et Néphrologie Centre de recherche du CHU de Québec-UniversitéLavalQuebecQCCanada département de médecine Facultéde MédecineUniversitéLavalQuebecQCCanada département de Psychiatrie et Neurosciences Facultéde MédecineQuebecQCCanada

There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after *** that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic ***,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal *** weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 *** this period,the animals had access to a running wheel,which they could use or *** acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars ***,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned *** to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal dOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned *** present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.

关键词： 6-hydroxydopamine dopamine dopamine transporter exercise neurorestoration Parkinson’s disease polyunsaturated fatty acids omega-3

mitochondria–cGAS–STING axis is a potential therapeutic target for senescence-dependent inflammaging-associated neurodegeneration

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Neural Regeneration Research 2025年第3期20卷 805-807页

作者： Josém.Izquierdo Centro de Biología molecular Severo Ochoa(CBm) Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid(CSIC-UAM)MadridSpain

The word “senescence” comes from the Latin senescens, meaning “to begin to age”, and is characterized by a long-lasting but reversible block in proliferation, resulting from stress-induced cell cycle arrest of pre... 详细信息

关键词： Latin potential lasting

Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander J.P.Goldschmidt damien d.Pearse W.dalton dietrich Allan d.Levi James d.Guest miller School of medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FdA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell