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Quantitative tracking of trans-synaptic nose-to-brain transport of nanoparticles and its modulation by odor,aging,and parkinson’s disease

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Nano Research 2023年第5期16卷 7119-7133页

作者： Alexander V.Romashchenko Dmitrii V.petrovskii Sergey Yu.Trotsky Ksenia N.Morozova Nina B.Illarionova Maria V.Zhukova Elena V.Kiseleva Marina B.Sharapova Daniil S.Zuev Konstantin E.Kuper Sergey Yu.Taskaev Anna I.Kasatova Dmitrii A.Kasatov Olga I.Solovieva Ivan A.Razumov Ludmila A.Gerlinskaya mikhail p.moshkin Yuri M.moshkin The Federal Research Center Institute of Cytology and Genetics SB RASAcademician Lavrentiev Avenue10Novosibirsk 630090Russia International tomography center Institutskaya st.3ANovosibirsk 630090Russia G.K.Boreskov Institute of Catalysis SB RASAcademician Lavrentiev Avenue5Novosibirsk 630090Russia The Federal Research Center Budker Institute of Nuclear physics SB RASAcademician Lavrentiev Avenue11Novosibirsk 630090Russia Institute of Computational Technologies Academician M.A.Lavrentiev avenue6Novosibirsk 630090Russia Institute of Gene Biology Russian Academy of SciencesMoscow 117334Russia Institute of Molecular and Cellular Biology SB RASAcad.Lavrentiev Ave8/2Novosibirsk 630090Russia Federal Research Centre of Biological Systems and Agrotechnologies RASst.January 929Orenburg 460000Russia

Nanoparticles(Nps)can be transported via the nose-to-brain(N_(2)B)***,quantitative data on their spatiotemporal dynamics and regulation of the N_(2)B transport are largely *** surveyed metal oxide/hydroxide Nps as magnetic resonance imaging(MRI)contrasts for quantitative N_(2)B *** containing divalent transition metals were the only ones capable of N_(2)B *** T1-weighted(T1W)MRI,we showed that Mn_(3)O_(4)-Nps were readily engulfed by olfactory receptor neurons(ORNs)without disrupting olfactory sensing,we mapped their N_(2)B *** neurons,the Mn_(3)O_(4)-Nps were localized to the cytosol,mitochondria,vesicles,moved at mixed fast and slow axonal transport velocities intraand extra-vesicularly through *** Nps’axonal transport is dependent on neuronal activity and microtubule *** Mn_(3)O_(4)-Nps were trans-synaptically transmitted through at least four synapses across the olfactory ***-synaptic transmission of the Nps was dependent on N-type Ca^(2+)channels and NMDA receptors but blocked by GABAB receptor activation.A five-parameter Weibull signal increase/decrease model fitted to the T1W MRI data allowed for estimating kinetic parameters of Mn_(3)O_(4)-Np accumulation/*** and relative accumulation rates,but not elimination,correlated negatively with the number of synapses from ORNs,indicating a coupling of the Nps’N_(2)B transport with spontaneous neuronal ***,olfactory stimuli(2,5-dimethylpyrazine and acetophenone)significantly modulated and rerouted the Mn_(3)O_(4)-Np N_(2)B transport odor ***,the Nps’trans-synaptic transmission was impaired by aging and the onset of parkinson’s *** data suggest new approaches to diagnostics,functional neuroimaging,controlling N_(2)B drug delivery.

关键词： Mn_(3)O_(4)nanoparticles magnetic resonance imaging(MRI) nose-to-brain transport trans-synaptic transmission olfactory stimulation

Unlocking hypoglycemia–associated brain microvascular dysfunction:critical insights from proteomic analysis

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Neural Regeneration Research 2025年第6期20卷 1707-1708页

作者： Siva S.V.p.Sakamuri Anil Sakamuri Department of Chemistry Auburn University at MontgomeryMontgomeryALUSA Vascular Biology Center and Department of Medicine Medical College of Georgia at Augusta UniversityAugustaGAUSA

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose levels below sta nda rd physiological *** hypoglycemia,classified as level 1 hypoglycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate *** hypoglycemia,denoted by blood glucose levels less than 54 mg/dL,poses a life-threatening risk if left *** with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

关键词： impaired intake critical

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

Adding new dimension to non-directed C（sp3）–H functionalizations

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Science China Chemistry 2025年

作者： Konstantin p.Bryliakov Laboratory of Selective Oxidation Catalysis N.D.Zelinsky Institute of Organic Chemistry RAS

Aliphatic C–H groups are among the most abundant yet least reactive functional groups in organic molecules. Nature has evolved metalloenzymes such as those of the cytochrome p450 superfamily that efficiently activate individual tertiary（3） and secondary （2） C（sp3）–H bonds in complex molecules with the highest level of regio-and stereoselectivity [1], thus encouraging studies aimed at engineering artificial metalloenzymes for synthetic applications [2].

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From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

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Neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital Nacional de parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for Neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural Regeneration Research 2025年第3期20卷 725-739页

作者： Benjamin R.Helmold Angela Ahrens Zachary Fitzgerald p.Hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SpAST spastin

Interactions between intruders and residents in the mole vole Ellobius talpinus

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动物学报 2004年第1期50卷 19-26页

作者： Eugene NOVIKOV Dmitry pETROVSKI Irene KOLOSOVA Stephan STEINLECHNER mikhail moshkin Institute of Animal Systematics and Ecology Siberian Branch of Russian Academy of SciencesFrunze Street 11630091Novosibirsk Russia Department of Zoology School of Veterinary MedicineHannoverGermany

We studied the behavioral and endocrine responses of the fossorial s ocial rodent, mole vole Ellobius talpinus pall., to intrusions of strangers int o burrow systems that were occupied by intact families. Both in reproductive and non-reproductive seasons, all intruders disappeared from the burrow systems of residents within two days of introduction, whereas 4 of 7 individuals introduced into empty burrows remained there at least for two days. Introduction of strang ers led to the concentration of residents at the point of release and to an incr ease of plasma corticosterone in both residents and intruders. During the breedi ng season, introduction of strangers was also accompanied by an increase of plas ma testosterone of residents on the day of introduction. Thus, simulation of int rusion of strangers demonstrated the efficient social fence of resident mole vol es that seems to be an important mechanism of stabilization of size and structur e of mole vole families. Encounters of residents and intruders resulted in activ ation of physiological mechanisms of stress, especially during the breeding seas on .

关键词： Fossorial rodents Mole vole Familiarity Social fence Stress

Impacts of pI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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Neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón pérez-Núñez María Fernanda González Ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(pI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the pI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/pI3K/AKT/connexin 43,and Notch/pI3K/AKT *** targeting the inactivation of the pI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the pI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

An application of space-filling curves to improve results of turbulent aerodynamics modeling with convolutional neural networks

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Chinese Journal of Aeronautics 2024年第2期37卷 81-92页

作者： mikhail pETROV Sofia ZIMINA Moscow Institute of physics&Technology Dolgoprudny 141701Russia

When carrying out calculations for turbulent flow simulation,one inevitably has to face the choice between accuracy and speed of *** order to simultaneously obtain both a computationally efficient and more accurate model,a surrogate model can be built on the basis of some fast special model and knowledge of previous calculations obtained by more accurate base models from various test bases or some results of serial *** objective of this work is to construct a surrogate model which allows to improve the accuracy of turbulent calculations obtained by a special model on unstructured *** this purpose,we use 1D Convolutional Neural Network(CNN)of the encoder-decoder architecture and reduce the problem to a single dimension by applying space-filling *** an approach would have the benefit of being applicable to solutions obtained on unstructured *** this work,a non-local approach is applied where entire flow fields obtained by the special and base models are used as input and ground truth output ***-Allmaras(SA)model and Near-wall Domain Decomposition(NDD)method for SA are taken as the base and special models *** efficiency and accuracy of the obtained surrogate model are demonstrated in a case of supersonic flow over a compression corner with different values for angleαand Reynolds number *** conducted an investigation into interpolation and extrapolation by Re and also into interpolation byα.

关键词： Space-filling curves Convolutional neural network Domain decomposition Turbulent flows Unstructured mesh