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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)

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Heterogeneity of mature oligodendrocytes in the central nervous system

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Neural Regeneration Research 2025年第5期20卷 1336-1349页

作者： Chao Weng Adam m.R.Groh moein Yaqubi Qiao-Ling Cui Jo Anne Stratton G.R.Wayne moore Jack P.Antel Neuroimmunology Unit Montreal Neurological Institute-HospitalDepartment of Neurology and NeurosurgeryMcGill UniversityMontrealQCCanada Department of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous *** evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to *** the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is *** delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature ***,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination ***,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system *** and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric ***,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined *** studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte *** research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,

关键词： aging central nervous system diseases electron microscopy heterogeneity immunohistochemistry myelin sheath natural history neuroglia oligodendroglia single-cell gene expression analysis

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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

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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

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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

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macular microvascular and structural changes on optical coherence tomography angiography in atypical optic neuritis

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World Journal of methodology 2025年第1期15卷 88-94页

作者： Chinmay mahatme madhurima Kaushik Veerappan Rathinasabapathy Saravanan Karthik Kumar Virna m Shah Department of General Ophthalmology Aravind Eye HospitalCoimbatore 641014Tamil NāduIndia Department of Neuro-ophthalmology Aravind Eye HospitalCoimbatore 641014Tamil NāduIndia Department of Vitreoretina Aravind Eye HospitalCoimbatore 641014Tamil NāduIndia

BACKGROUND Atypical optic neuritis,consisting of neuromyelitis optica spectrum disorders(NmOSD)or myelin oligodendrocyte glycoprotein antibody disease(mOGAD),has a very similar presentation but different prognostic implications and longterm management *** and metabolic factors are being thought to play a role in such autoimmune neuro-inflammatory disorders,apart from the obvious immune mediated *** the advent of optical coherence tomography angiography(OCTA),it is easy to pick up on these subclinical macular microvascular and structural *** To study the macular microvascular and structural changes on OCTA in atypical optic *** This observational cross-sectional study involved 8 NmOSD and 17 mOGAD patients,diagnosed serologically,as well as 10 healthy *** vascular density(mVD)and ganglion cell+inner plexiform layer thickness(GCIPL)were studied using *** There was a significant reduction in mVD in NmOSD and mOGAD affected as well as unaffected eyes when compared with healthy *** and mOGAD affected eyes had significant GCIPL thinning compared with healthy *** unaffected eyes did not show significant GCIPL thinning compared to healthy controls in contrast to mOGAD unaffected *** comparing NmOSD with mOGAD,there was no significant difference in terms of mVD or GCIPL in the affected or unaffected *** Although significant microvascular and structural changes are present on OCTA between atypical optic neuritis and normal patients,they could not help in differentiating between NmOSD and mOGAD cases.

关键词： Optical coherence tomography angiography Atypical optic neuritis macular microvascular changes Neuromyelitis optica spectrum disorders myelin oligodendrocyte glycoprotein antibody disorder

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Getting physical with medical education:Exercise based virtual anatomy review classes for medical students

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World Journal of methodology 2025年第1期15卷 20-25页

作者： Nadeesha R Samarasinghe Taniya S Nagpal michele L Barbeau Charys m martin Division of General Surgery Faculty of MedicineUniversity of British ColumbiaVancouver V6T 1Z3BCCanada Faculty of Kinesiology Sport and RecreationUniversity of AlbertaEdmonton T6G 2R3ABCanada Anatomy and Cell Biology University of Western OntarioLondon N6A 3K7ONCanada Department of Anatomy and Cell Biology Schulich School of Medicine and DentistryThe University of Western OntarioLondon N6A 3K7ONCanada

The benefits of regular physical activity are well ***,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary *** investigate the incorporation of PA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(mSK)anatomy course *** synchronous sessions were co-taught by a group fitness instructor and an anatomy *** fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously *** the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving mSK anatomy knowledge,PA levels,and mental *** participants completed surveys;a majority agreed that the classes increased understanding of mSK concepts(90.0%)and activity levels(97.7%).many(70.0%)felt that the classes helped reduce *** majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social ***,medical students saw benefit in PA based interventions to supplement mSK course *** with increasing activity levels and promoting health behaviours,integrating PA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.

关键词： medical education musculoskeletal Anatomy Exercise Online learning

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Structural, elastic and electronic properties for m_2 XC (m=Ti and Cr, X=Ga and Al) phases from ab initio calculations

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Acta metallurgica Sinica(English Letters) 2011年第4期24卷 255-270页

作者： B. Ghebouli m.A. Ghebouli m. Fatmi N. Bouarissa m. Benkerri I.A. Ibrahim Laboratory of Study of Surfaces and Interfaces of Solids materials Department of Physics Faculty of Science University of Setif Department of Physics University Center Research Unit on Emerging materials Ferhat Abbas University of Setif Department of Physics Faculty of Sciences King Khalid University Central metallurgical Research and Development Institute P.O. Box: 87 Helwan 11424 Cairo Egypt

The first-principles study of the structural, elastic and electronic properties of the m2XC phases depending on the type of m transition metal （m are Ti and Cr） and on X （X are Ga and A1） was reported. The calculations are performed using the pseudo-potential plane-wave approach in both the local density and generalized gradient approximations. The elastic constants are calculated using the static finite strain technique. Features such as structural and elastic parameters, Debye tem- perature, sound velocities and their pressure dependence have been investigated. In agreement with experimental and previous theoretical findings, it is found that the compressibility along a and c axis depends on the valence electron concentration （VEC）. Correlations revealing the governing role of the X and m elements on the machinability indices of the material have been examined. The electronic properties have been discussed in terms of chemical bonding showing that bonding is due to md-Cp and md-Xp hybridizations. m-C bonds are stiffer than m-X ones and A1-Ti （Cr-C） bonds are stiffer than those corresponding to Ti-C （A1-Cr）. It is shown that the stiffness of the m-X and m-C bonds increases with increasing the number of VEC.

关键词： m2XC phases ab initio Pressure effect Band structures

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Influence of FCA Welding Process Parameters on Distortion of 409m Stainless Steel for Rail Coach Building

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Journal of Iron and Steel Research International 2013年第1期20卷 71-78页

作者： m V Venkatesan N murugan B m Prasad A manickavasagam Department of mechanical Engineering Coimbatore Institute of TechnologyCoimbatore 641014TNIndia Integral Coach Factory Indian RailwaysChennai 600038TNIndia

The influence of flux cored arc welding （FCAW） process parameters such as welding current, travel speed, voltage and CO2 shielding gas flow rate on bowing distortion of 409m ferritic stainless steel sheets of 2 mm in thickness was discussed. The bowing distortions of the welded plates were measured using a simple device called profile tracer. An experimental regression equation was developed to predict the bowing distortion and with this equation, it is easy to select optimized process parameters to achieve minimum bowing distortion. It is revealed that the FCAW process parameters have significant influence on bead profile and the bowing distortion.

关键词： bowing distortion ferritic stainless steel flux cored arc welding statistical model rail coach distortion measurement

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Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily Firas Kobeissy Juanmarco Gutierrez Gonzalez Daniel Refai Gerald R.Rodts Christian mustroph David Gimbel Jonathan Grossberg Daniel L.Barrow matthew F.Gary Ali m.Alawieh Department of Neurosurgery Emory University School of MedicineAtlantaGAUSA Department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this *** the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing *** this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the *** study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular *** effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord *** this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human *** review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

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