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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

Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

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neural Regeneration Research 2025年第10期20卷 2969-2981页

作者： mackenzie m.Spicer Jianqi Yang Daniel Fu Alison n.DeVore marisol Lauffer nilufer S.Atasoy Deniz Atasoy Rory A.Fisher Department of neuroscience and Pharmacology University of Iowa Carver College of MedicineIowa CityIAUSA Iowa neuroscience Institute University of Iowa Carver College of MedicineIowa CityIAUSA Interdisciplinary Graduate Program in molecular medicine University of Iowa Carver College of MedicineIowa CityIAUSA neural Circuits and Behavior Core University of Iowa Carver College of MedicineIowa CityIAUSA

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s *** hippocampal neurogenesis is reduced in patients with Alzheimer’s *** stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s ***,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly ***,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in ***,we generated novel RGS6fl/fl;APP_(SWe) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse *** found that voluntary running in APP_(SWe) mice restored their hippocampal cognitive impairments to that of control *** cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal *** hippocampal neurogenesis was reduced in sedentary APP_(SWe) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor ***6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing ***,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWe) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

关键词： adult hippocampal neurogenesis Alzheimer’s disease dentate gyrus exercise learning/memory neural precursor cells regulator of G protein signaling 6(RGS6)

Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro martín-Belmonte Sergi Ferré Francisco Ciruela Synaptic Structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs Víctor Cilleros-mañé Laia Just-Borràs marta Balanyà-Segura Aleksandra Polishchuk Laura nadal marta Tomàs Carolina Silvera-Simón manel m.Santafé maria A.Lanuza Unitat d’Histologia i neurobiologia(UHneurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75nTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the n-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

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neural Regeneration Research 2025年第3期20卷 660-670页

作者： ernesto Doncel-Pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital nacional de Parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain medical Research Unit for neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

The role of tree uprooting in the transporting of sediment and mixing of soil in the Tatra mountains

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Journal of mountain Science 2021年第1期18卷 38-50页

作者： dariusz STRZYŻOWSKI Institute of Geography and Spatial management Jagiellonian UniversityGronostajowa 7Kraków 30-387Poland

Tree uprooting is an important process which leads to many geomorphic *** of the most important are the transport of sediment and mixing of *** aim of this article is to make a detailed examination of the magnitude of sediment transport caused by an extreme windthrow event in three severely affected ***,a comparison is made of the windthrow event with a mass movement event in the aspect of the magnitude of sediment transport and soil *** study was conducted in three second-to third-order catchments in the Tatra mountains,where a strong foehn wind event caused extensive windthrow in 2013,and a high-magnitude rainfall event triggered mass movements in *** volume of sediment uplifted by the uprooting event was calculated based on the mapping of root plates using high-resolution(0.04 m)aerial images and measurements of root plate volumes conducted in the *** volume of sediment transported by shallow landslides was determined based on a Digital elevation model(Dem1-m resolution).Windthrows affected 34%,76%,and94%of the area of the investigated *** of the trees had fallen *** direction of treefall was influenced by the slope aspect and *** plates and pits covered 1.3%,4.8%,and 5.4%of the area of the *** flux generated by the uprooting event,calculated for the entire area of each investigated catchment ranged from 8.1×10^(–4) to 9.9×10^(–3) m^(3) m^(–1) event^(–1).This was notably lower than the sediment flux generated by the mass movement event(also calculated for the entire area of each catchment),which was 1.8-6.1×10^(–2)m^(3) m^(–1) event^(–1).By contrast,uprooting affected a much larger area than the mass movement event,which underlines its significant role in the mixing of soil.

关键词： Tree uprooting Windthrow event Slope processes Sediment flux Tatra mountains

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

A full vectorial mapping of nanophotonic light fields

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Light(Science & Applications) 2019年第1期8卷 961-967页

作者： B.le Feber J.e.Sipe m.Wulf L.Kuipers n.Rotenberg Optical materials engineering Laboratory ETH Zurich8092 ZurichSwitzerland Center for nanophotonics AMOLFScience Park 1041098 XG AmsterdamThe Netherlands Institute for Optical Sciences University of Toronto60 St.George StreetOntario M5S 1A7Canada Institute of Science and Technology Austria Am Campus 13400 KlosterneuburgAustria Kavli Institute of nanoscience Department of Quantum NanoscienceDelft University of TechnologyLorentzweg 12628 CJ DelftThe Netherlands niels Bohr Institute and Center for Hybrid Quantum networks University of CopenhagenBlegdamsvej 17DK-2100 CopenhagenDenmark

Light is a union of electric and magnetic fields,and nowhere is the complex relationship between these fields more evident than in the near fields of nanophotonic ***,complicated electric and magnetic fields varying over subwavelength scales are generally present,which results in photonic phenomena such as extraordinary optical momentum,superchiral fields,and a complex spatial evolution of optical *** understanding of such phenomena requires nanoscale measurements of the complete optical field *** the sensitivity of nearfield scanning optical microscopy to the complete electromagnetic field was recently demonstrated,a separation of different components required a priori knowledge of the ***,we introduce a robust algorithm that can disentangle all six electric and magnetic field components from a single near-field measurement without any numerical modeling of the *** examples,we unravel the fields of two prototypical nanophotonic structures:a photonic crystal waveguide and a plasmonic *** results pave the way for new studies of complex photonic phenomena at the nanoscale and for the design of structures that optimize their optical behavior.

关键词： waveguide fields mapping

Optimal Control Policy of m/G/1 Queueing System with Delayed Randomized multiple Vacations Under the modified min(n,D)-Policy Control

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Journal of the Operations Research Society of China 2023年第4期11卷 857-874页

作者： le Luo Ying-Hui Tang miao-miao Yu Wen-Qing Wu School of mathematical Sciences Sichuan Normal UniversityChengdu610068SichuanChina nanchong Vocational and Technical College Nanchong637000JiangsuChina Visual Computing and Virtual Reality Key Laboratory of Sichuan Province Sichuan Normal UniversityChengdu610068SichuanChina

Based on the number of customers and the server’s workload,this paper proposes a modified min(n,D)-policy and discusses an m/G/1 queueing model with delayed randomized multiple vacations under such a *** the well-known stochastic decomposition property of the steady-state queue size,the probability generating function of the steady-state queue length distribution is ***,the explicit expressions of the expected queue length and the additional queue length distribution are derived by some algebraic ***,employing the renewal reward theorem,the explicit expression of the long-run expected cost per unit time is ***,we analyze the optimal policy for economizing the expected cost and compare the optimal min(n,D)-policy with the optimal n-policy and the optimal D-policy by using numerical examples.

关键词： m/G/1 queue modified min(n,D)-policy Randomized multiple vacations Queue length generating function Optimal joint control policy