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Investigation of Pain Mechanisms by Calcium Imaging Approaches

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neuroscience Bulletin 2018年第1期34卷 194-199页

作者： Michael Anderson Qin Zheng Xinzhong Dong The solomon h.snyder department of neuroscience Center for Sensory Biology School of Medicine Johns Hopkins University howard hughes Medical Institute School of Medicine Johns Hopkins University

Due to the complex circuitry and plethora of cell types involved in somatosensation, it is becoming increasingly important to be able to observe cellular activity at the population level. In addition, since cells rely on an intricate variety of extracellular factors, it is important to strive to maintain the physiological environment. Many electrophysiological techniques require the implementation of artificially-produced physiological environments and it can be difficult to assess the activity of many cells simultane- ously. Moreover, imaging Ca^2＋ transients using Ca^2＋- sensitive dyes often requires in vitro preparations or in vivo injections, which can lead to variable expression levels. With the development of more sensitive geneticallyencoded Ca^2＋ indicators （GECIs） it is now possible to observe changes in Ca^2＋ transients in large populations of cells at the same time. Recently, groups have used a GECI called GCaMP to address fundamental questions in somatosensation. Researchers can now induce GCaMP expression in the mouse genome using viral or gene knock- in approaches and observe the activity of populations of cells in the pain pathway such as dorsal root ganglia （DRG）, spinal neurons, or glia. This approach can be used in vivo and thus maintains the organism＇s biological integrity. The implementation of GCaMP imaging has led to many advances in our understanding of somatosensation. here, we review the current findings in pain research using GCaMP imaging as well as discussing potential method- ological considerations.

关键词： DRG Spinal cord GCaMP imaging Pain pathways Neural circuit

Locus coeruleus-norepinephrine: basic functions and insights into Parkinson’s disease

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Neural Regeneration Research 2020年第6期15卷 1006-1013页

作者： Bilal Abdul Bari Varun Chokshi Katharina Schmidt The solomon h.snyder department of neuroscience Brain Science InstituteKavli Neuroscience Discovery InstituteThe Johns Hopkins University School of MedicineBaltimoreMDUSA department of Physiology The Johns Hopkins University School of MedicineBaltimoreMDUSA

The locus coeruleus is a pontine nucleus that produces much of the brain's *** its small size,the locus coeruleus is critical for a myriad of functions and is involved in many neurodegenerative and neuropsychiatric *** this review,we discuss the physiology and anatomy of the locus coeruleus system and focus on norepinephrine's role in synaptic *** highlight Parkinson's disease as a disorder with motor and neuropsychiatric symptoms that may be understood as aberrations in the normal functions of locus coeruleus.

关键词： catecholamines copper neurodegenerative diseases neuromodulation neuronal circuits neuropsychiatric symptoms noradrenaline synaptic plasticity

Closed-loop control of epileptiform activities in a neural population model using a proportional-derivative controller

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Chinese Physics B 2015年第3期24卷 434-441页

作者：王俊松王美丽李小俚 Ernst Niebur School of Biomedical Engineering Tianjin Medical University Zanvyl Krieger Mind/Brain Institute and solomon snyder department of neuroscience Johns Hopkins University National Key Laboratory of Cognitive neuroscience and Learning Beijing Normal University

Epilepsy is believed to be caused by a lack of balance between excitation and inhibitation in the brain. A promising strategy for the control of the disease is closed-loop brain stimulation. how to determine the stimulation control parameters for effective and safe treatment protocols remains, however, an unsolved question. To constrain the complex dynamics of the biological brain, we use a neural population model（NPM）. We propose that a proportional-derivative（PD） type closed-loop control can successfully suppress epileptiform activities. First, we determine the stability of root loci, which reveals that the dynamical mechanism underlying epilepsy in the NPM is the loss of homeostatic control caused by the lack of balance between excitation and inhibition. Then, we design a PD type closed-loop controller to stabilize the unstable NPM such that the homeostatic equilibriums are maintained; we show that epileptiform activities are successfully suppressed. A graphical approach is employed to determine the stabilizing region of the PD controller in the parameter space, providing a theoretical guideline for the selection of the PD control parameters. Furthermore, we establish the relationship between the control parameters and the model parameters in the form of stabilizing regions to help understand the mechanism of suppressing epileptiform activities in the NPM. Simulations show that the PD-type closed-loop control strategy can effectively suppress epileptiform activities in the NPM.

关键词： neural population model epileptiform activities proportional-derivative controller stabilizing region

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

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

Sialylation of TLR2 initiates osteoclast fusion

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Bone Research 2022年第2期10卷 286-296页

作者： Ce Dou Gehua Zhen Yang Dan Mei Wan Nathachit Limjunyawong Xu Cao department of Orthopedic Surgery Institute of Cell Engineering and Department of Biomedical EngineeringJohns Hopkins University School of MedicineBaltimoreMDUSA The solomon h.snyder department of neuroscience Johns Hopkins University School of MedicineBaltimoreMDUSA

The molecular control of osteoclast formation is still not clearly elucidated. here, we show that a process of cell recognition mediated by Siglec15-TLR2 binding is indispensable and occurs prior to cell fusion in RANKL-mediated osteoclastogenesis. Siglec15 has been shown to regulate osteoclastic bone resorption. however, the receptor for Siglec15 has not been identified, and the signaling mechanism involving Siglec15 in osteoclast function remains unclear. We found that Siglec15 bound sialylated TLR2 as its receptor and that the binding of sialylated TLR2 to Siglec15 in macrophages committed to the osteoclast-lineage initiated cell fusion for osteoclast formation, in which sialic acid was transferred by the sialyltransferase ST3 Gal1. Interestingly, the expression of Siglec15 in macrophages was activated by M-CSF, whereas ST3 Gal1 expression was induced by RANKL. Both Siglec15-specific deletion in macrophages and intrafemoral injection of sialidase abrogated cell recognition and reduced subsequent cell fusion for the formation of osteoclasts, resulting in increased bone formation in mice. Thus, our results reveal that cell recognition mediated by the binding of sialylated TLR2 to Siglec15 initiates cell fusion for osteoclast formation.

关键词： osteoclast TLR2 injection

Signaling pathways that regulate axon regeneration

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neuroscience Bulletin 2013年第4期29卷 411-420页

作者： Saijilafu Bo-Yin Zhang Feng-Quan Zhou department of Orthopaedic Surgery The Johns Hopkins University department of The solomon h. snyder department of neuroscience The Johns Hopkins University

Neurons in the mammalian central nervous system （CNS） cannot regenerate axons after injury. In contrast, neurons in the mammalian peripheral nervous system and in some non-mammalian models, such as C. elegans and Drosophila, are able to regrow axons. Understanding the molecular mechanisms by which these neurons support axon regeneration will help us find ways to enhance mammalian CNS axon regeneration. here, recent studies in which signaling pathways regulating naturally-occurring axon regeneration that have been identified are reviewed, focusing on how these pathways control gene expression and growth-cone function during axon regeneration.

关键词： axon regeneration axonal growth signal transduction

heterologous expression of bovine lactoferrin C‑lobe in Bacillus subtilis and comparison of its antibacterial activity with N‑lobe

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Systems Microbiology and Biomanufacturing 2022年第2期2卷 345-354页

作者： Liang Jin Lihong Li Wenchi Zhang Rongzhen Zhang Yan Xu The Key Laboratory of Industrial Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi 214122China solomon h.snyder department of neuroscience Johns Hopkins University School of MedicineBaltimoreMD 21205USA

The natural concentration of bovine lactoferrin C-lobe is low and its separation by proteolytic enzyme digestion is ***,we expressed the codon-optimized fragment of C-lobe on plasmid pMA0911 with the P_(veg) promoter in Bacillus subtilis 168 at 20℃.The yield was 7.5 mg/L,and 90.6%purity was achieved using ammonium sulfate precipitation,Ni–NTA and molecular *** C-lobe at 10 mg/mL completely inhibited cell growth of Escherichia coli JM109(DE3)and Pseudomonas aeruginosa CGMCC 1.6740,and 48.4%of growth of Staphylococcus aureus CGMCC 1.282,the result is similar to that of 200 ng/mL *** minimum inhibitory concentrations of C-lobe were 4,8 and 16 mg/mL,while those of N-lobe were 128,256 and 512μg/mL for ***,*** and ***,*** is the frst report on bovine lactoferrin C-lobe expression and the comparative resistance of the recombinant N-and C-lobes in a food-safe strain of *** fndings ofer the potential to study the structure–function relationship of the N-and C-lobes recombinantly produced in the same host.

关键词： Bovine lactoferrin C-lobe Bacillus subtilis Expression and purifcation Codon optimization Antibacterial activity Comparative resistance

Transcription Factor MAFA Regulates Mechanical Sensation by Modulating Piezo2 Expression

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neuroscience Bulletin 2022年第8期38卷 933-937页

作者： Chang-ming Wang Dustin P.Green Xinzhong Dong The solomon h.snyder department of neuroscience Johns Hopkins University School of MedicineBaltimoreMD21205USA department of neuroscience Cell Biologyand AnatomyUniversity of Texas Medical BranchGalvestonTXUSA solomon h.snyder department of neuroscience Johns Hopkins University School of MedicineBaltimoreMD21205USA department of Dermatology Johns Hopkins University School of MedicineBaltimoreMD21205USA department of Neurosurgery Johns Hopkins University School of MedicineBaltimoreMD21205USA howard hughes Medical Institute Chevy ChaseMDUSA

Dear Editor,Essential for survival,mechanical sensation is detected and transmited to the spinal cord by primary sensory afferents and their cell bodies located in the dorsal root ganglia(DRG).Multiple types of mechanically sensitive DRG neurons have been identified that mediate various mechanosensation modalities(***-painful versus painful).

关键词： sensation modalities Essential