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Presenilin mutations and their impact on neuronal differentiation in Alzheimer’s disease

Neural Regeneration Research 2022年第1期17卷 31-37页

作者： mercedes A.Hernández-Sapiéns Edwin E.Reza-Zaldívar ana l.márquez-aguirre Ulises Gómez-Pinedo Jorge matias-Guiu Ricardo R.Cevallos Juan C.mateos-Díaz Víctor J.Sánchez-González Alejandro A.Canales-aguirre Unidad de Evaluación Preclínica Unidad de Biotecnología Médica y FarmacéuticaCentro de Investigación y Asistencia en Tecnología y Diseño del Estado de JaliscoGuadalajaraMéxico Instituto de Neurociencias IdISSCHospital Clínico San CarlosMadridEspaña Biochemistry and molecular Genetics Department University of AlabamaBirminghamAlabama Unidad de Biotecnología Industrial Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de JaliscoGuadalajaraMéxico Centro Universitario de los Altos Universidad de GuadalajaraGuadalajaraMéxico

The presenilin genes(PSEN1 and PSEN2)are mainly responsible for causing early-onset familial Alzheimer’s disease,harboring~300 causative mutations,and representing~90%of all.mutations associated with a very aggressive disease form.Presenilin 1 is the catalytic core of theγ-secretase complex that conducts the intramembranous proteolytic excision of multiple transmembrane proteins like the amyloid precursor protein,Notch-1,N-and E-cadherin,lRP,Syndecan,Delta,Jagged,CD44,ErbB4,and Nectin1a.Presenilin 1 plays an essential role in neural progenitor maintenance,neurogenesis,neurite outgrowth,synaptic function,neuronal function,myelination,and plasticity.Therefore,an imbalance caused by mutations in presenilin 1/γ-secretase might cause aberrant signaling,synaptic dysfunction,memory impairment,and increased Aβ42/Aβ40 ratio,contributing to neurodegeneration during the initial stages of Alzheimer’s disease pathogenesis.This review focuses on the neuronal differentiation dysregulation mediated by PSEN1 mutations in Alzheimer’s disease.Furthermore,we emphasize the importance of Alzheimer’s disease-induced pluripotent stem cells models in analyzing PSEN1 mutations implication over the early stages of the Alzheimer’s disease pathogenesis throughout neuronal differentiation impairment.

关键词： familial Alzheimer’s disease familial Alzheimer’s disease-induced pluripotent stem cells models induced pluripotent stem cells neurogenesis neuronal differentiation Notch presenilin 1 PSEN1 mutations γ-secretase complex

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Sex differences in Alzheimer's disease:an urgent research venue to follow

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Neural Regeneration Research 2024年第12期19卷 2569-2570页

作者： Raquel Jiménez-Herrera ana Contreras Juan D.Navarro-lópez lydia Jiménez-Díaz Neurophysiology&Behavior lab University of Castilla-La ManchaSchool of Medicine of Ciudad RealCiudad RealSpain

Due to increasing life expectancy,the amount of people with dementia worldwide is expected to experience a substantial rise,with estimates indicating a growth from 55 million in 2019 to a staggering 139 million by the year 2050.Among the various forms of dementia.Alzheimer's disease(AD)stands out as the predominant and most prevalent.

关键词： Alzheimer predominant estimates

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mesenchymal stem cell-derived exosomes promote neurogenesis and cognitive function recovery in a mouse model of Alzheimer’s disease

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Neural Regeneration Research 2019年第9期14卷 1626-1634页

作者： Edwin E. Reza-Zaldivar mercedes A. Hernández-Sapiéns Yanet K. Gutiérrez-mercado Sergio Sandoval-ávila Ulises Gomez-Pinedo ana l. márquez-aguirre Estefanía Vázquez-méndez Eduardo Padilla-Camberos Alejandro A. Canales-aguirre Unidad de Evaluation Preclinica Unidad de Biotecnologia Medica y FarmaceuticaCentro de Investigation y Asistencia en Tecnologia y Diseno del Estado de JaliscoGuadalajaraMexico Regenerative medicine Unit Neuroscience InstituteDepartment of Neurosurgery and NeurologyIdlSSC Health Research Institute of the Hospital Clinico San CarlosMadridSpain

Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease.Alzheimer’s disease mouse models were established by injection of beta amyloid 1?42 aggregates into dentate gyrus bilaterally.morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration.Afterwards,neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAm antibodies.Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1?42-induced cognitive impairment,and these effects are similar to those shown in the mesenchymal stem cells.These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease.All procedures and experiments were approved by Institutional Animal Care and Use Committee(CICUAl)(approval No.CICUAl 2016-011)on April 25,2016.

关键词： Alzheimer’s disease neurodegenerative disease cognitive impairment memory Alzheimer’s disease mouse model mesenchymal stem cell exosomes neurogenesis cognitive improvement cell-free therapy neural regeneration

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Impact of payment source, referral site, and place of residence on outcomes after allogeneic transplantation in mexico

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World Journal of Transplantation 2024年第2期14卷 76-87页

作者： Andrés Gómez-De león Yesica A lópez-mora Valeria García-Zárate ana Varela-Constantino Sergio U Villegas-De leon Xitlaly J González-leal Raúl del Toro-mijares Anna C Rodríguez-Zúñiga Juan F Barrios-Ruiz Victor mingura-ledezma Perla R Colunga-Pedraza Olga G Cantú-Rodríguez César H Gutiérrez-aguirre luz Tarín-Arzaga Elías E González-lópez David Gómez-Almaguer Hematology Service Universidad Autónoma de Nuevo LeónFacultad de Medicina y Hospital Universitario Dr.JoséEleuterio GonzálezMonterrey 64460Nuevo LeónMexico Hemato-logy Service Clínica Gómez AlmaguerMonterrey 64710Nuevo LeónMexico Hematology Service Instituto Tecnológico de Estudios Superiores de MonterreyTec SaludEscuela de Medicina Ignacio SantosMonterrey 64710Nuevo LeónMexico

BACKGROUND The impact of social determinants of health in allogeneic transplant recipients in low-and middle-income countries is poorly described.This observational study analyzes the impact of place of residence,referring institution,and transplant cost coverage(out-of-pocket vs government-funded vs private insurance)on outcomes after allogeneic hematopoietic stem cell transplantation(alloHSCT)in two of mexico's largest public and private institutions.AIm To evaluate the impact of social determinants of health and their relationship with outcomes among allogeneic transplant recipients in mexico.mETHODS In this retrospective cohort study,we included adolescents and adults≥16 years who received a matched sibling or haploidentical transplant from 2015-2022.Participants were selected without regard to their diagnosis and were sourced from both a private clinic and a public University Hospital in mexico.Three payment groups were compared:Out-of-pocket(OOP),private insurance,and a federal Universal healthcare program“Seguro Popular”.Outcomes were compared between referred and institution-diagnosed patients,and between residents of Nuevo leon and out-of-state.Primary outcomes included overall survival(OS),categorized by residence,referral,and payment source.Secondary outcomes encompassed early mortality,event-free-survival,graft-versus-host-relapse-free survival,and non-relapse-mortality(NRm).Statistical analyses employed appropriate tests,Kaplan-meier method,and Cox proportional hazard regression modeling.Statistical software included SPSS and R with tidycmprsk library.RESUlTS Our primary outcome was overall survival.We included 287 patients,n=164 who lived out of state(57.1%),and n=129 referred from another institution(44.9%).The most frequent payment source was OOP(n=139,48.4%),followed by private insurance(n=75,26.1%)and universal coverage(n=73,25.4%).No differences in OS,event-free-survival,NRm,or graft-versus-host-relapse-free survival were observed for patients diagnosed locally vs in another institution,nor pat

关键词： Hematopoietic cell transplant Social determinants of health Geography Haploidentical Out-of-pocket Financial toxicity Survival Health services and outcomes Hematopoietic malignancy Aplastic anemia

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Knowledge Is Invented: Addressing Invention and the Art of Saying in the Psychoanalytic Field

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Philosophy Study 2024年第3期14卷 97-105页

作者： ana lúcia mandelli de marsillac Universidade Federal de Santa Catarina FlorianópolisBrasil

In the Freudian-lacanian field,there is an important distinction between knowledge and truth.The truth,of an unconscious nature,is something that inhabits us,directs us,but that escapes us.Knowledge,in turn,is something to be invented,from the hole of the Real,the Unconscious truth,and the subjective experience.The relationships between playing,creating,and fantasizing;the dimension of the uncanny,fiction,and imagination in subjectivity;the invention of knowledge of oneself,derived from the pains and flavors of being who one is,are creative dimensions that inhabit the subject,permeate the analytical act,and transversalize psychoanalysis.In the practice,we listen to and witness processes of analysis that awaken an invention/reinvention of oneself,in the process of remembering,repeating,and elaborating,but also in what the transference relationship summons.Knowledge of oneself,does not guarantee a life without mishaps,sadness,and illusions,but allows the invention and recognition of knowledge and a style.The concept of Sinthome(2007),coined by Jacques lacan,comes in the wake of the processes of self-invention and is a knowing-doing with the symptom,with the paradoxes of joyful suffering,producing,as a result,an art of saying.Therefore,in this communication,I will articulate el.ments of theory,practice,and psychoanalytic experience that allow us to expand knowledge of the themes of invention and imagination articulated with the concept of sinthome,their relationships with subjectivity,and the direction of psychoanalytic treatment.

关键词： psychoanalysis invention imagination knowledge sinthome

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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso Josémartínez-Hernández Alejandro martín-Belmonte Rocío Alfaro-Ruiz miriam Fernández ana Esther moreno-martínez mar Cuadrado-Tejedor ana García-Osta Rafael luján Synaptic Structure laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hal.marks can retain cognitive function.Unraveling the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic targets.Our hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD animals.Utilizing the morris Water maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 mice.While the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant fraction.To further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic methods.Our findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic controls.Intriguingly,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate receptors.Specifically,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic controls.Notably,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic mice.These subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play crucial roles in the mechanisms of cognitive resil

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

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Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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Neural Regeneration Research 2024年第11期19卷 2532-2542页

作者： Aina Bellver-Sanchis Pedro AAvila-lópez Iva Tic David Valle-García marta Ribalta-Vilella luis labrador Deb Ranjan Banerjee ana Guerrero Gemma Casadesus Coralie Poulard mercè Pallàs Christian Grinán-Ferré Department of Pharmacology and Therapeutic Chemistry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and molecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Institute of Biotechnology National Autonomous University of MexicoCuernavacaMexico Department of Pharmacology and Therapeutics Health Science Center-University of FloridaGainesvilleFLUSA Department of Chemistry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia Cancer Research Cancer lyon Universitéde LyonLyonFrance Inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRS UmR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Investigación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neuroimmunology Department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic infl.mmation and oxidative stress.likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinfl.mmation.To better understand the biology of G9a,we compared the global.microRNA expression between senescence-accelerated mouse-prone 8(SAmP8)control.mice and SAmP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAmP8 group treated with G9a inhibitor than in the SAmP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AmPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRNAs miR-128 peroxisome-proliferator activator receptorγ(PPARγ) PPARG SAmP8

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Vanadium mineralization at los Chihuidos sediment-hosted Cu-V deposit,Neuquén Basin,Argentina:An approach to vanadium ore forming processes

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Geoscience Frontiers 2024年第1期15卷 225-246页

作者： ana l.Rainoldi Daniel Beaufort marta B.Franchini Adolfo Giusiano Sabine Petit Patricia Patrier m.Josefina Pons Dpto.de Geología Universidad Nacional del Sur(UNS)8000 Bahía BlancaArgentina Consejo Nacional de Investigaciones Científicas y Técnicas Centro Patagónico de Estudios MetalogenéticosArgentina Universitéde Poitiers IC2MPCNRS-UMR 7285HydrasaF-86022 Poitiers CedexFrance Universidad Nacional del Comahue Facultad de IngenieríaDepartamento de Geología y Petróleo8300 NeuquénArgentina Consultant Geologist 8300 NeuquénArgentina Universidad Nacional de Río Negro Instituto de Investigación en Paleobiología y GeologíaRío NegroArgentina

Vanadium mineralization at los Chihuidos deposit of the Neuquén Basin is linked to the development of a redox front system related to the inflow of hydrocarbons into the red sandstone of the Huincul Formation.Interaction of hydrocarbons with oxidized red beds and connate water generated redox reactions where hematite was dissolved due to iron reduction resulting in the discoloration of the red strata.At the contact between oxidized red sandstone and reduced white sandstone,precipitation of specific mineral phases resulted in the V ore with minor amounts of Cu.With the impl.mentation of the redox interface,abundant V-montmorillonite and V-hematite precipitated at the more oxidizing conditions and Cu-V-corrensite-type at the more reducing conditions of the redox front.As the redox front advanced with fluids constantly migrating into the reservoir,more reducing conditions were stablished,promoting chloritization and minor illitization with V-Cu incorporation and continuous upgrading of the ore.main ore mineralogy consists of clay minerals including V-bearing montmorillonite,Cu-V-corrensite-type,V-di-trioctahedral chlorite and Cu-tri-trioctahedral chlorite with minor V-illite-smectite mixed-layer minerals and associated secondary V-hematite.Chloritization over illitization was favored due to high amounts of Fe and mg in detrital clasts and in connate fluids and by low K availability related to low amounts of detrital K-feldspar.The spatial transition of V and/or Cu bearing clay minerals observed through the mineralized redox front at los Chihuidos deposit(kaolinite→smectite→illite/smectite→corrensite-type→di-trioctahedral-chlorite→tri-trioctahedral-chlorite)and the related variation of V-Cu concentrations in bulk rock are indicative of increasing pH and decreasing Eh of resident solutions from red to white sandstones during the hypogene mineralization process.late influx of Cu-rich oxidized basinal brines precipitated main copper ore with Cu-sulfides in the white sandstone up to the contact with the redox front in co

关键词： Clay minerals V-chlorite Redox front Bleaching Hydrocarbons

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A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities

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military medical Research 2024年第2期11卷 228-267页

作者： miguel A.Ortega Oscar Fraile-martinez Cielo García-montero Sergio Haro miguel Ángel Álvarez-mon Diego De leon-Oliva ana m.Gomez-lahoz Jorge monserrat mar Atienza-Pérez David Díaz Elisa lopez-Dolado melchor Álvarez-mon Department of medicine and medical Specialities University of Alcala28801 Alcala de HenaresSpain Ramón y Cajal Institute of Sanitary Research(IRYCIS) 28034 MadridSpain Department of Psychiatry and mental Health Hospital Universitario Infanta Leonor28031 MadridSpain Service of Rehabilitation National Hospital for Paraplegic PatientsCarr.de la PeraledaS/N45004 ToledoSpain Immune System Diseases‑Rheumatology Service and Internal.medicine University Hospital Príncipe de Asturias(CIBEREHD)28806 Alcala de HenaresSpain

Spinal cord injury(SCI)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological.mechanisms directed to ameliorate neural damage but also exacerbate initial damage(secondary injury).The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI,explaining the progression and detrimental consequences related to this condition.Psychoneuroimmunoendocrinology(PNIE)is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism,considering the mind and the body as a whole.The initial traumatic event and the consequent neurological disruption trigger immune,endocrine,and multisystem dysfunction,which in turn affect the patient's psyche and well-being.In the present review,we will explore the most important local and systemic consequences of SCI from a PNIE perspective,defining the changes occurring in each system and how all these mechanisms are interconnected.Finally,potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical.management of these patients.

关键词： Spinal cord injury(SCI) Psychoneuroimmunoendocrinology(PNIE) Secondary injury Immunoinfl.mmatory dysfunction Gut microbiota Translational opportunities

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棒与星系整体恒星形成性质关系的统计研究

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天文学进展 2024年第1期42卷 115-127页

作者：穆子豪沈世银 Rafael S.de Souza ana l.Chies-Santos 中国科学院上海天文台星系宇宙学重点实验室上海200030 中国科学院大学北京100049 星系和宇宙学半解析研究重点实验室上海200034 赫特福德大学天体物理研究中心英国哈特菲尔德学院巷AL109AB 南里奥格兰德州联邦大学科学研究所巴西阿雷格里港9500

盘状星系中的棒结构特征与星系自身所处环境及整体恒星形成特征之间存在复杂的相互关系。利用细致的星系形态特征测量计划Galaxy Zoo DECalS中的数据构建了一组目前最大的具有同样恒星质量分布的强棒、弱棒和无棒星系样本。通过引入星... 详细信息

盘状星系中的棒结构特征与星系自身所处环境及整体恒星形成特征之间存在复杂的相互关系。利用细致的星系形态特征测量计划Galaxy Zoo DECalS中的数据构建了一组目前最大的具有同样恒星质量分布的强棒、弱棒和无棒星系样本。通过引入星系所处暗晕质量及相空间特征来控制星系所处的环境效应之后,进一步对比研究强棒、弱棒和无棒星系的恒星形成特征。研究表明,有棒星系中的恒星形成熄灭的比例系统地高于无棒星系,且强棒的效应更为明显。但是,对于仍处于恒星形成主序上的星系来说,强棒、弱棒和无棒星系的恒星形成特征并没有显著差别。以上结果表明,星系中的棒特征在其存在的时标中可能使部分星系迅速地从恒星形成转入熄灭状态。

关键词：棒旋星系恒星形成环境

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