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

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

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Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

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Neural Regeneration Research 2025年第1期20卷 41-53页

作者： Alessio Canovai Pete A.Williams department of biology University of PisaPisaItaly department of Clinical neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/*** quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary *** quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many *** this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian *** the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and *** quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully ***,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological *** addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

关键词： metabolism mitochondria neurodegenerative disease neuroprotection pyrroloquinoline quinone retinal diseases

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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

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Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord

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Neural Regeneration Research 2025年第7期20卷 2095-2107页

作者： Emily A.Hibbard Liwen Zhou Cathy Z.Yang Karthik Venkudusamy Yessenia Montoya Alexa Olivarez George D.Bittner Dale R.Sengelaub Program in neuroscience Indiana UniversityBloomingtonINUSA department of neuroscience University of Texas at AustinAustinTXUSA

Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically *** used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic *** have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor ***,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target *** this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic *** adult male and female rats(Sprague–Dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of *** action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury *** success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days *** 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish ***-fusion repair reestablished axonal *** to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal ***,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repa

关键词： axotomy dorsal horn peripheral nerve injury plasticity polyethylene glycol(PEG) sciatic nerve sensory terminals wheat germ agglutinin horseradish peroxidase

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Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

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Neural Regeneration Research 2025年第11期20卷 3063-3075页

作者： Stephen Vidman Yee Hang Ethan Ma Nolan Fullenkamp Giles W.Plant department of neuroscience Ohio State UniversityColumbusOHUSA

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative *** the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained *** work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as *** embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns *** barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem *** advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal *** precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed *** the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma *** of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of *** the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor ***,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support ***,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for *** to a clinical setting wi

关键词： axon regeneration central nervous system regeneration induced pluripotent stem cells neurotrauma regenerative medicine spinal cord injury stem cell therapy

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Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

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Neural Regeneration Research 2025年第9期20卷 2667-2681页

作者： Liwen Zhou Karthik Venkudusamy Emily A.Hibbard Yessenia Montoya Alexa Olivarez Cathy Z.Yang Adelaide Leung Varun Gokhale Guhan Periyasamy Zeal Pathak Dale R.Sengelaub George D.Bittner department of neuroscience University of TexasAustinTXUSA Program in neuroscience Indiana UniversityBloomingtonINUSA department of Molecular Biosciences University of TexasAustinTXUSA

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian Degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary *** preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion *** the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis *** nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the *** von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve *** withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not *** thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated *** sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the ***,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative

关键词： autophagia axotomy collateral sprouting neuropathic pain peripheral nerve repair polyethylene glycol fusion(PEG-fusion) saphenous nerve sensory neurons sex and strain Wallerian degeneration

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Calcium-sensitive protein MLC1 as a possible modulator of the astrocyte functional state

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Neural Regeneration Research 2025年第7期20卷 2008-2010页

作者： Elena Ambrosini Angela Lanciotti Maria Stefania Brignone department of neuroscience Istituto Superiore di SanitàRomeItaly

Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult *** maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.

关键词： alterations modulator maintain

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Regeneration mechanisms and therapeutic strategies for neuromuscular junctions in aging and diseases

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Neural Regeneration Research 2025年第1期20卷 193-194页

作者： Masashi Fujitani Abu Md Mamun Tarif Yoshinori Otani department of Anatomy and neuroscience Faculty of MedicineShimane UniversityShimaneJapan

The neuromuscular junction(NMJ)is an essential synaptic structure composed of motor neurons,skeletal muscles,and glial cells that orchestrate the critical process of muscle contraction(Li et al.,2018).The typical NMJ structure is classically described as having a“pretzel-like”shape in mice(Figure 1),whereas human NMJs have a smaller,fragmented structure throughout *** NMJs exhibit smaller or fragmented endplates,partial denervation,reduced numbers of synaptic vesicles,abnormal presynaptic mitochondria,and dysfunctional perisynaptic Schwann cells(Alhindi et al.,2022).

关键词： aging structure Figure

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From mice to humans:a need for comparable results in mammalian neuroplasticity

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Neural Regeneration Research 2025年第2期20卷 464-466页

作者： Marco Ghibaudi Enrica Boda Luca Bonfanti neuroscience Institute Cavalieri Ottolenghi OrbassanoItaly department of Veterinary Sciences University of TurinTurinItaly department of neuroscience Rita Levi-Montalcini University of TurinTurinItaly

Brain plasticity-A universal tool with many variations:The study of brain plasticity has been gaining interest since almost a century and has now reached a huge amount of information(>80,000 results in PubMed).Overall,different types of plasticity,including stem cell-driven genesis of new neurons(adult neurogenesis),cells in arrested maturation(dormant neurons),neuro-glial and synaptic plasticity,can coexist and contribute to grant plastic changes in the brain,from a cellular to system level(Benedetti and Couillard-Despres,2022;Bonfanti et al.,2023).

关键词： plasticity al. arrest

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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang John Marshall department of Molecular biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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