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TET1 Participates in Complete Freund’s Adjuvant-induced Trigeminal Inflammatory Pain by Regulating Kv7.2 in a Mouse Model

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neuroscience Bulletin 2024年第6期40卷 707-718页

作者： Dengcheng Zhan Jingjing Zhang Songxue Su Xiuhua Ren Sen Zhao Weidong Zang Jing Cao department of Human anatomy School of Basic Medical SciencesZhengzhou UniversityZhengzhou450001China neuroscience Research Institute Zhengzhou UniversityZhengzhou450001China

Trigeminal inflammatory pain is one of the most severe pain-related disorders in humans;however,the underlying mechanisms remain largely *** this study,we investigated the possible contribution of interaction between ten-eleven translocation methylcytosine dioxygenase 1(TET1)and the voltage-gated K^(+)channel Kv7.2(encoded by Kcnq2)to orofacial inflammatory pain in *** found that complete Freund’s adjuvant(CFA)injection reduced the expression of Kcnq2/Kv7.2 in the trigeminal ganglion(TG)and induced orofacial inflammatory *** involvement of Kv7.2 in CFA-induced orofacial pain was further confirmed by Kv7.2 knockdown or ***,TET1 knockdown in Tet1^(flox/flox)mice significantly reduced the expression of Kv7.2 and M currents in the TG and led to pain-like ***,TET1 overexpression by lentivirus rescued the CFA-induced decreases of Kcnq2 and M currents and alleviated mechanical *** data suggest that TET1 is implicated in CFA-induced trigeminal inflammatory pain by positively regulating Kv7.2 in TG neurons.

关键词： Facial pain KCNQ2 potassium channel TET1 protein

Unraveling the potential of acute intermittent hypoxia as a strategy for inducing robust repair in multiple sclerosis

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Neural Regeneration Research 2024年第11期19卷 2339-2340页

作者： Valerie M.K.Verge Nataliya Tokarska Justin M.Naniong department of anatomy Physiology and PharmacologyUniversity of SaskatchewanSaskatoonSKCanada Cameco MS neuroscience Research Center University of SaskatchewanSaskatoonSKCanada

Multiple sclerosis(MS)is a debilitating inflammatory disease of the central nervous system characterized by immune-mediated segmental demyelination and variable degrees of axonal and neuronal degeneration that contribute to *** efficient and effective repair programs following demyelination is a major goal and challenge in *** MS therapies focus largely on modulating the immune aspects of the disease contributing to *** this alleviates some symptoms and mitigates damage,it does not tackle the fundamental challenge of effective remyelination,which few MS patients experience,especially in the progressive phase of the disease.

关键词： sclerosis degeneration damage

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

Blood-brain barrier pathology in cerebral small vessel disease

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Neural Regeneration Research 2024年第6期19卷 1233-1240页

作者： Ruxue Jia Gemma Solé-Guardia Amanda J.Kiliaan department of Medical Imaging AnatomyRadboud University Medical CenterDonders Institute for BrainCognition&BehaviorCenter for Medical NeurosciencePreclinical Imaging Center PRIMERadboud Alzheimer CenterNijmegenthe Netherlands

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the *** at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of *** signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease *** pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier ***,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel ***,the purpose of this review is to provide a new foundation in the study of small vessel disease ***,we discuss the main structural domains and functions of the blood-brain ***,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel ***,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

关键词： blood-brain barrier dysfunction cerebral blood flow cerebral hypoperfusion endothelial dysfunction hypertension inflammation magnetic resonance imaging neurovascular unit oxidative stress small vessel disease tight junctions transcytosis

The physiological role of the unfolded protein response in the nervous system

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Neural Regeneration Research 2024年第11期19卷 2411-2420页

作者： Shuangchan Wu Wensheng Lin department of neuroscience University of MinnesotaMinneapolisMNUSA Institute for Translational neuroscience University of MinnesotaMinneapolisMNUSA

The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded *** UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein *** also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum *** research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous ***,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.

关键词： myelin neuron oligodendrocyte Schwann cell unfolded protein response

Changes in structural plasticity of hippocampal neurons in an animal model of multiple sclerosis

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Zoological Research 2024年第2期45卷 398-414页

作者： Poornima D.E.Weerasinghe-Mudiyanselage Sohi Kang Joong-Sun Kim Sung-Ho Kim Hongbing Wang Taekyun Shin Changjong Moon department of Veterinary anatomy and Animal Behavior College of Veterinary Medicine and BK21 FOUR ProgramChonnam National UniversityGwangju 61186Republic of Korea department of anatomy and Convergence Medical Science Institute of Health SciencesCollege of MedicineGyeongsang National UniversityJinju 52727Republic of Korea department of Physiology and neuroscience Program Michigan State UniversityEast LansingMI 48824USA department of Veterinary anatomy College of Veterinary Medicine and Veterinary Medical Research InstituteJeju National UniversityJeju 63243Republic of Korea

Structural plasticity is critical for the functional diversity of neurons in the *** autoimmune encephalomyelitis(EAE)is the most commonly used model for multiple sclerosis(MS),successfully mimicking its key pathological features(inflammation,demyelination,axonal loss,and gliosis)and clinical symptoms(motor and non-motordysfunctions).Recentstudieshave demonstrated the importance of synaptic plasticity in EAE *** the present study,we investigated the features of behavioral alteration and hippocampal structural plasticity in EAE-affected mice in the early phase(11 days post-immunization,DPI)and chronic phase(28DPI).EAE-affected mice exhibited hippocampus-related behavioral dysfunction in the open field test during both early and chronic *** complexity was largely affected in the cornu ammonis 1(CA1)and CA3 apical and dentate gyrus(DG)subregions of the hippocampus during the chronic phase,while this effect was only noted in the CA1 apical subregion in the early ***,dendritic spine density was reduced in the hippocampal CA1 and CA3 apical/basal and DG subregions in the early phase of EAE,but only reduced in the DG subregion during the chronic ***,mRNA levels of proinflammatory cytokines(Il1β,Tnfα,and Ifnγ)and glial cell markers(Gfap and Cd68)were significantly increased,whereas the expression of activity-regulated cytoskeletonassociated protein(ARC)was reduced during the chronic ***,exposure to the aforementioned cytokines in primary cultures of hippocampal neurons reduced dendritic complexity and ARC *** cultures of hippocampal neurons also showed significantly reduced extracellular signal-regulated kinase(ERK)phosphorylation upon treatment with proinflammatory ***,these results suggest that autoimmune neuroinflammation alters structural plasticity in the hippocampus,possibly through the ERK-ARC pathway,indicating that this alteration may be associated with hi

关键词： Activity-regulated cytoskeleton-associated protein Anxiety-like behavior Experimental autoimmune encephalomyelitis Hippocampal dysfunction Neuroinflammation

Adenosine A_(2A)receptor blockade attenuates excitotoxicity in rat striatal medium spiny neurons during an ischemic-like insult

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Neural Regeneration Research 2024年第2期19卷 255-257页

作者： Elisabetta Coppi Federica Cherchi Alasdair J.Gibb department of neuroscience PsychologyDrug Research and Child HealthUniversity of FlorenceFlorenceItaly department of neuroscience Physiology and PharmacologyUniversity College LondonLondonUK

During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue ***,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy *** neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic *** indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 *** recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose *** demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor *** present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.

关键词： adenosine A_(2A)receptors anoxic depolarization brain ischemia glutamate excitotoxicity medium spiny neurons oxygen and glucose deprivation

Premature axon-oligodendrocyte interaction contributes to stalling of experimental axon regeneration after injury to the white matter

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Neural Regeneration Research 2024年第3期19卷 469-470页

作者： Ephraim F.Trakhtenberg department of neuroscience University of Connecticut School of MedicineFarmingtonCTUSA

Studies from nearly 3 decades ago suggested that,in the central nervous system(CNS),myelination of axons by oligodendrocytes not only helps improve axonal conductivity but also stabilizes circuitry(Colello and Schwab,1994).Over the years,myelin sheaths produced by oligodendrocytes have been found to contain multiple molecules that are inhibitory to axonal growth(e.g.,MAG,NogoA,OMgp,Semaphorins)(Yiu and He,2006;Silver et al.,2014).After white matter injury in the adult CNS,myelin debris from damaged axons and dead oligodendrocytes accumulates in the forming glial scar and exposes these myelin-associated axon growth-inhibitory molecules to the injured axonal stumps,thereby contributing to the inhibition of axonal *** development,CNS axons reach their postsynaptic targets and stop growing before oligodendrocytes appear and myelinate them(Foran and Peterson,1992;Dangata et al.,1996).Therefore,myelin-associated axon growth-inhibitory molecules interacting with already grown axons during myelination were thought to block axons from promiscuous sprouting and miswiring,thereby stabilizing neural circuitry in the CNS(Colello and Schwab,1994).

关键词： thereby white injury

Beyond functional MRI signals:molecular and cellular modifiers of the functional connectome and cognition

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Neural Regeneration Research 2024年第5期19卷 937-938页

作者： Lorenzo Pini Alessandro Salvalaggio Maurizio Corbetta Padova neuroscience Center University of PadovaItaly Veneto Institute of Molecular Medicine VIMMPadovaItaly department of neuroscience University of PadovaItaly

Our brain is constantly *** at rest,the brain carries out essential functions such as maintenance of resting potentials,subthreshold synaptic activity,and spiking activity related to information *** resting activity can be assessed with several in vivo tools,such as resting-state functional magnetic resonance *** technique measures subtle changes in blood flow,volume,and oxygenation that occur over *** vascular in nature,resting-state functional magnetic resonance imaging is considered a reliable proxy of neural activity and several studies have shown that the brain is functionally divided into interacting neural networks called the“functional connectome”.

关键词： functional neural measures