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Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

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Neural Regeneration research 2025年第9期20卷 2706-2726页

作者： Biao Xiao Chaoyang Chu Zhicheng Lin Tianyuan Fang Yuyu Zhou Chuxia Zhang Jianghui Shan Shiyu Chen Liping Li Department of Physiology and Pharmacology Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Ningbo Key Laboratory of Behavioral Neuroscience Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Key Laboratory of Addiction research of Zhejiang Province NingboZhejiang ProvinceChina

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's ***,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and ***,nonpharmacological interventions aimed at inducing adult neurogenesis are currently *** individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully *** this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 *** deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease ***,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus *** findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 ***,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice

关键词： acousto-optic stimulation adult neurogenesis Alzheimer's disease amyloid precursor protein/presenilin 1 mice amyloid-beta deposition brain cell apoptosis cognitive impairment depression-like behavior involuntary treadmill exercise olfactory stimulation serum metabolites

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Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration research 2025年第9期20卷 2624-2632页

作者： Jangampalli Adi Pradeepkiran Priyanka Rawat Arubala P.Reddy Erika Orlov PHemachandra Reddy Department of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA Department of Nutritional Sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA Department of Pharmacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA Department of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA Department of Speech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA Department of Public health Texas Tech University Health Sciences CenterLubbockTXUSA

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)*** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-***,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule

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Glial response in the midcingulate cortex in Huntington’s disease

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Neural Regeneration research 2025年第1期20卷 207-208页

作者： Thulani H.Palpagama Andrea Kwakowsky center for Brain research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and Therapeutics School of MedicineGalway Neuroscience CenterUniversity of GalwayGalwayIreland

Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and *** can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive *** causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.

关键词： Huntington degeneration cortex

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New insights on the role of chondroitin sulfate proteoglycans in neural stem cell–mediated repair in spinal cord injury

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Neural Regeneration research 2025年第6期20卷 1699-1700页

作者： Seyed Mojtaba Hosseini Soheila Karimi-Abdolrezaee Department of Physiology and Pathophysiology Spinal Cord Research CentreRady Faculty of Health SciencesUniversity of ManitobaWinnipegMBCanada Manitoba Multiple Sclerosis research center WinnipegMBCanada Children Hospital research Institute of Manitoba WinnipegMBCanada

Extensive neurodegeneration is a hallmark of traumatic spinal cord injury (SCI) that underlies permanent sensorimotor and autonomic impairments (Alizadeh et al.,2019).Following the primary impact,the spinal cord undergoes a cascade of secondary injury mechanisms that are driven by disruption of the blood-spinal cord ba rrier,vascula r inju ry,glial reactivity,neu roinfla mmation,oxidative stress,lipid peroxidation,and glutamate excitotoxicity that culminate in neuronal and oligodendroglial cell death,demyelination,and axonal damage(Alizadeh et al.,2019).To achieve a meaningful functional recovery after SCI,regeneration of new neurons and oligodendrocytes and their successful growth and integration within the neural network are critical steps for reconstructing the damaged spinal cord tissue (Fischer et al.,2020).

关键词： peroxidation Fischer injury

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Co-production of hydrogen, oxygen, and electricity via an integrated solar-driven system with decoupled water electrolyzer and Na-Zn ion battery

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Journal of Energy Chemistry 2025年第1期100卷 621-627页

作者： Fei Lv Longjie Liu Jiazhe Wu Pengfei Wang Lixia Pan Dengwei Jing Yubin Chen International research center for Renewable Energy State Key Laboratory of Multiphase Flow in Power Engineering Xi'an Jiaotong University

Combining water electrolysis and rechargeable battery technologies into a single system holds great promise for the co-production of hydrogen （H2） and ***,the design and development of such systems is still in its ***,an integrated hydrogen-oxygen （O2）-electricity co-production system featuring a bipolar membrane-assisted decoupled electrolyzer and a Na-Zn ion battery was established with sodium nickelhexacyanoferrate （NaNiHCF） and Zn2+/Zn as dual redox *** decoupled electrolyzer enables to produce H2and O2in different time and space with almost 100%Faradaic efficiency at 100 mA ***,the charged NaNiHCF and Zn electrodes after the electrolysis processes formed a Na-Zn ion battery,which can generate electricity with an average cell voltage of 1.75 V at 10 m A *** connecting Si photovoltaics with the modular electrochemical device,a well-matched solar driven system was built to convert the intermittent solar energy into hydrogen and electric energy with a solar to hydrogen-electricity efficiency of 16.7%,demonstrating the flexible storage and conversion of renewables.

关键词： Hydrogen Electricity Decoupled water electrolyzer Na-Zn ion battery Solar energy

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Cortical hem signaling center: functions, development, and potential implications for evolution and brain disorders

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Neural Regeneration research 2025年第4期20卷 1079-1080页

作者： Victor V.Chizhikov Igor Y.Iskusnykh Department of Anatomy and Neurobiology University of Tennessee Health Science CenterMemphisTNUSA

Development of the telencephalon relies upon several signaling centers-localized cellular populations that supply secreted factors to pattern the cortical *** such signaling center is the cortical hem,which arises during embryonic development at the telencephalic dorsal midline,adjacent to the choroid plexus and hippocampal primordium(Figure 1A).While the cortical hem has also been described in reptiles and birds,most of our knowledge about the developmental roles of the cortical hem is derived from the analysis in *** cortical hem produces several types of secreted molecules,including wingless-related integration site(Wnt)and bone morphogenetic(Bmp)*** cortical hem is particularly important for the development of the hippocampus,which is involved in learning and memory,and the neocortex,which is the most complex brain region that mediates multiple types of behavior and higher cognitive functions(Mangale et al.,2008;Dal-Valle-Anton and Borrell,2022).

关键词： epithelium Figure center

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Neuroinflammation as a therapeutic target in Huntington's disease

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Neural Regeneration research 2025年第3期20卷 817-818页

作者： Andrea Kwakowsky Thulani H.Palpagama center for Brain research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and Therapeutics School of MedicineGalway Neuroscience CentreUniversity of GalwayGalwayIreland

In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.

关键词： Huntington inflammation Medicine

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Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

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Neural Regeneration research 2025年第6期20卷 1541-1554页

作者： Jinmei Ye Cong Duan Jiaxin Han Jinrong Chen Ning Sun Yuan Li Tifei Yuan Daihui Peng Division of Mood Disorder Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychiatry First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Shanghai Key Laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Co-Innovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

关键词： biomarker cytokine exosomes inflammasome major depressive disorder microglia mitochondrial DNA mitochondrial dysfunction neuroinflammation Toll-like receptor

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Therapeutic potential of exercise-hormone irisin in Alzheimer's disease

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Neural Regeneration research 2025年第6期20卷 1555-1564页

作者： Eunhee Kim Rudolph ETanzi Se Hoon Choi Genetics and Aging research Unit MassGeneral Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMAUSA McCance center for Brain health Massachusetts General HospitalBostonMAUSA

Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.

关键词： Alzheimer's disease exercise fibronectin typeⅢdomain-containing protein 5(FNDC5) irisin

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Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

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Neural Regeneration research 2025年第11期20卷 3144-3150页

作者： Holly Flyger Samantha J.Holdsworth Alistair J.Gunn Laura Bennet Hamid Abbasi Mātai Medical research Institute Tairāwhiti GisborneNew Zealand Department of Anatomy&Medical Imaging Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand center for Brain research The University of AucklandAucklandNew Zealand Auckland Bioengineering Institute The University of AucklandAucklandNew Zealand

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental *** assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and *** present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic *** review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent *** review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic *** challenges limit the timing consistency,particularly the need for intensive care and clinical ***,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after *** suggests that in the future it will be important to explore a wider range of times after hypo

关键词： magnetic resonance imaging neonatal hypoxic-ischemic encephalopathy neurodevelopmental outcomes prognostic biomarkers in neuroimaging scan timing therapeutic hypothermia

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