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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

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

Emerging insights into the function of very long chain fatty acids at cerebellar synapses

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Neural Regeneration Research 2025年第6期20卷 1709-1710页

作者： Martin-Paul Agbaga Mohiuddin Ahmad department of cell biology and Ophthalmology University of Oklahoma Health Sciences Centerand Dean McGee Eye InstituteOklahoma CityOKUSA

Very long chain-saturated and-polyunsaturated fatty acids(VLC-SFA and VLC-PUFA, respectively) are a functionally important class of fatty acids containing 28 carbons or more in their acyl chain. They are synthesized by the elongation of very long fatty acids-4(ELOVL4) enzyme, expressed mainly in the brain, retina, skin, testes, and meibomian gland, where these fatty acids are found(Agbaga et al., 2008). Further, these organs exhibit tissuespecific VLC-PUFA and VLC-SFA biosynthesis and incorporation into complex lipids for specific functions. In the brain, skin, and Meibomian glands, the ELOVL4 mainly makes VLC-SFA, which are incorporated into complex sphingolipids. In the retina, the ELOVL4 makes VLC-PUFA that are incorporated into phosphatidylcholine, that are critical for visual function, while in testes and sperm, the VLC-PUFA are incorporated into sphingolipids that are critical for fertility(Yeboah et al., 2021).

关键词： functions function insight

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

In vivo direct neuronal conversion as a therapeutic strategy for ischemic stroke

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Neural Regeneration Research 2025年第8期20卷 2309-2310页

作者： Takashi Irie Taito Matsuda department of Stem cell biology and Medicine Graduate School of Medical SciencesKyushu UniversityFukuokaJapan department of Neurology Neurological InstituteGraduate School of Medical SciencesKyushu UniversityFukuokaJapan

Stroke causes neuronal loss,which ultimately results in persistent neurological ***,stroke was the third-leading cause of death and disability combined in all ages in 2019,after neonatal disorders and ischemic heart *** that year,there were 12.2 million incident strokes,101 million prevalent strokes,and 143 million disability-adjusted life-years due to stroke.

关键词： neonatal death therapeutic

Single-cell and spatial omics:exploring hypothalamic heterogeneity

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Neural Regeneration Research 2025年第6期20卷 1525-1540页

作者： Muhammad Junaid Eun Jeong Lee Su Bin Lim department of biochemistry&Molecular biology Ajou University School of MedicineSuwonSouth Korea department of Biomedical Sciences Graduate School of Ajou UniversitySuwonSouth Korea department of Brain Science Ajou University School of MedicineSuwonSouth Korea

Elucidating the complex dynamic cellular organization in the hypothalamus is critical for understanding its role in coordinating fundamental body functions. Over the past decade, single-cell and spatial omics technologies have significantly evolved, overcoming initial technical challenges in capturing and analyzing individual cells. These high-throughput omics technologies now offer a remarkable opportunity to comprehend the complex spatiotemporal patterns of transcriptional diversity and cell-type characteristics across the entire hypothalamus. Current single-cell and single-nucleus RNA sequencing methods comprehensively quantify gene expression by exploring distinct phenotypes across various subregions of the hypothalamus. However, single-cell/single-nucleus RNA sequencing requires isolating the cell/nuclei from the tissue, potentially resulting in the loss of spatial information concerning neuronal networks. Spatial transcriptomics methods, by bypassing the cell dissociation, can elucidate the intricate spatial organization of neural networks through their imaging and sequencing technologies. In this review, we highlight the applicative value of single-cell and spatial transcriptomics in exploring the complex molecular-genetic diversity of hypothalamic cell types, driven by recent high-throughput achievements.

关键词： cellular diversity hypothalamus multi-omics single-cell transcriptomics spatial transcriptomics

Translational challenges in amyotrophic lateral sclerosis therapy with macrophage migration inhibitory factor

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Neural Regeneration Research 2025年第9期20卷 2583-2584页

作者： Leenor Alfahel Aleksandar Rajkovic Adrian Israelson department of Physiology and cell biology Faculty of Health SciencesBen-Gurion University of the NegevBeer ShevaIsraelThe School of Brain Sciences and CognitionBen-Gurion University of the NegevBeer ShevaIsrael

Macrophage migration inhibitory factor(MIF):MIF acts as a pleiotropic inflammatory mediator,playing regulatory roles in innate and adaptive immunity,neuroinflammation,neuroendocrine functions,and nervous system development(Matejuk et al.,2024).In recent years,MIF has attra cted significant inte rest from research groups as a potential target for the treatment of various neurodegenerative diseases,including Alzheimer's disease,Parkinson's disease,multiple sclerosis,and glioblastoma(Matejuk et al.,2024).

关键词： immunity sclerosis

Neuroinflammation revisited through the microglial lens

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Neural Regeneration Research 2025年第7期20卷 1989-1990页

作者： Renato Socodato João B.Relvas Institute of Research and Innovation in Health(i3S)and Institute for Molecular and cell biology(IBMC) University of PortoPortoPortugal department of Biomedicine Faculty of Medicine of the University of Porto(FMUP)PortoPortugal

Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune *** exploration is particularly significant in understanding microglia,the CNS’s innate immune cells,beyond the conventional conflation of“neuroinflammation”and“microglial activation.”This conflation has clouded the true complexity of these processes,potentially stalling scientific progress and the development of new *** challenge the long-standing perspectives that have oversimplified these interactions,advocating for a deeper exploration of the dynamic relationship between neuroinflammation and microglial *** dissecting specific molecular pathways,we aim to illuminate their elaborate roles in neuroinflammatory responses,especially in the context of Alzheimer’s disease(AD).Here,neuroinflammation is not merely a passive observer or a direct antagonist but a complex agent in the disease’s *** article calls for a significant paradigm shift towards an integrative,multi-omics approach to *** such a comprehensive framework is crucial for advancing our understanding of neuroinflammatory conditions and paving the way for targeted therapeutic strategies for brain diseases.

关键词： inflammation simplified activation

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