114 results on '"Susuki K"'
Search Results
2. Intractable chronic inflammatory demyelinating polyneuropathy treated successfully with ciclosporin
- Author
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Odaka, M., Tatsumoto, M., Susuki, K., Hirata, K., and Yuki, N.
- Subjects
Prednisolone -- Observations ,Polyneuropathies -- Drug therapy ,Cyclosporine -- Patient outcomes ,Health ,Psychology and mental health - Published
- 2005
3. ‘ANKYRIN' THE PARANODE: S02-04
- Author
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Chang, K.-J., Zollinger, D., Susuki, K., Ho, T., Cooper, E. C., Mohler, P. J., Bennett, V., and Rasband, M. N.
- Published
- 2013
4. Three mechanisms assemble central nervous system nodes of Ranvier: S13–04
- Author
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Susuki, K., Chang, K. J., Zollinger, D., Liu, Y., Ogawa, Y., Eshed-Eisenbach, Y., Dours-Zimmerman, M., Oses-Prieto, J., Burlingame, A., Seidenbecher, C., Zimmerman, D., Oohashi, T., Pelés, E., and Rasband, M. N.
- Published
- 2013
5. CHARACTERIZATION OF THE SPECTRIN-BASED CYTOSKELETON IN MYELINATING GLIAL CELLS: YIC02-04
- Author
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Susuki, K.
- Published
- 2009
6. THE EXTRACELLULAR MATRIX AND CNS NODES OF RANVIER: C01-03
- Author
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Rasband, M. N., Ogawa, Y., and Susuki, K.
- Published
- 2009
7. COMPLEMENT INHIBITOR PREVENTS SODIUM CHANNEL DISRUPTION IN ACUTE MOTOR AXONAL NEUROPATHY MODEL
- Author
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Phongsisay, V, Susuki, K, Yamahashi, T, Okamoto, S, Funakoshi, K, Hirata, K, Matsuno, K, Shinoda, M, and Yuki, N
- Published
- 2008
8. Rhinolalia after diarrhea: a sole motor symptom occurring in post-infectious neuropathy associated with anti-ganglioside antibodies
- Author
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Kamitani, T., Kuroiwa, Y., Susuki, K., Kishida, H., Miyazaki, Y., and Yuki, N.
- Published
- 2006
9. GANGLIOSIDES ARE IMPORTANT FOR FORMATION AND MAINTENANCE OF ION CHANNEL CLUSTERS IN MYELINATED PERIPHERAL NERVES
- Author
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Susuki, K, Baba, H, Tohyama, K, Furukawa, K, Hirata, K, and Yuki, N
- Published
- 2005
10. Post-infectious acute ataxia and facial diplegia associated with anti-GD1a IgG antibody
- Author
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Galassi, G., Susuki, K., Quaglino, D., and Yuki, N.
- Published
- 2004
11. Overlapping Guillain-Barré syndrome and Bickerstaff's brainstem encephalitis associated with anti-GQ1b IgG antibody after herpes simplex virus infection
- Author
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Yuki, N., Susuki, K., Odaka, M., and Hirata, K.
- Published
- 2001
12. Leukocyte and complement activation by GM1-specific antibodies is associated with acute motor axonal neuropathy in rabbits
- Author
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Sorge, N.M. van, Yuki, N., Jansen, M.D., Nishimoto, Y., Susuki, K., Wokke, J.H., Winkel, J.G.J. van de, and Berg, L.H. van den
- Subjects
carbohydrates (lipids) ,Geneeskunde ,Econometric and Statistical Methods: General ,Immunology ,lipids (amino acids, peptides, and proteins) ,algemeen onderzoek ,Geneeskunde(GENK) ,General [Econometric and Statistical Methods] - Abstract
Acute motor axonal neuropathy (AMAN) in humans is associated with the presence of GM1-specific antibodies. Immunization of rabbits with GM1-containing ganglioside mixtures, purified GM1, or Campylobacter jejuni lipo-oligosaccharide exhibiting a GM1-like structure elicits GM1-specific antibodies, but axonal polyneuropathy only occurs in a subset of animals. This study aimed to dissect the molecular basis for the variable induction of AMAN in rabbits. Therefore, we analyzed the pro-inflammatory characteristics of GM1-specific antibodies in plasma samples from ganglioside-immunized rabbits with and without neurological deficits. GM1-specific plasma samples from all rabbits with AMAN were capable of activating both complement and leukocytes, in contrast to none of the plasma samples from rabbits without paralysis. Furthermore, GM1-specific IgG-mediated activation of leukocytes was detected before the onset of clinical signs. These data suggest that AMAN only occurs in rabbits that develop GM1-specific antibodies with pro-inflammatory properties.
- Published
- 2007
13. Ganglioside-specific IgG and IgA recruit leukocyte effector functions in Guillain-Barre syndrome
- Author
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Sorge, N.M. van, Yuki, N., Koga, M., Susuki, K., Jansen, M.D., Kooten, C. van, Wokke, J.H., Winkel, J.G.J. van de, Pol, W.L. van der, and Berg, L.H. van den
- Subjects
Geneeskunde ,Econometric and Statistical Methods: General ,Immunology ,Geneeskunde(GENK) ,General [Econometric and Statistical Methods] ,Algemeen onderzoek - Abstract
The capacity of ganglioside-specific autoantibodies to recruit leukocyte effector functions was studied. Serum samples from 87 patients with Guillain–Barré (GBS) or Miller Fisher syndrome (MFS), containing GM1-, GQ1b-, or GD1b-specific IgG or IgA, were tested for leukocyte activating capacity. Ganglioside-specific IgG antibodies generally induced leukocyte activation, irrespective of specificity. The magnitude of leukocyte degranulation correlated with GM1- and GQ1b-specific IgG titers, but not with disease severity. Finally, GM1- specific IgA activated leukocytes through the IgA receptor, FcαRI (CD89). Therefore, both ganglioside-specific IgG and IgA can recruit leukocyte effector functions, which may be relevant in the pathogenesis of GBS and MFS. © 2006 Elsevier B.V. All rights reserved. Keywords: Guillain–Barré syndrome; Autoantibodies; Pathogenicity; Gangliosides; FcγR
- Published
- 2007
14. Effect of methylprednisolone in patients with Guillain-Barré syndrome [2] (multiple letters)
- Author
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Susuki, K., Yuki, N., Rossi, G., Locatelli, F., Van Doorn, P. A., Van Koningsveld, R., and Schmitz, P. I. M.
- Published
- 2004
15. Acute facial diplegia and hyperreflexia: A Guillain-Barré syndrome variant.
- Author
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Susuki K, Atsumi M, Koga M, Hirata K, Yuki N, Susuki, K, Atsumi, M, Koga, M, Hirata, K, and Yuki, N
- Published
- 2004
- Full Text
- View/download PDF
16. Acute motor axonal neuropathy after Mycoplasma infection: Evidence of molecular mimicry.
- Author
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Susuki, K, Odaka, M, Mori, M, Hirata, K, and Yuki, N
- Published
- 2004
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17. Effect of methylprednisolone in patients with Guillain-Barré syndrome.
- Author
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Susuki K, Yuki N, Rossi G, Locatelli F, van Doorn PA, van Koningsveld R, and Schmitz PIM
- Published
- 2004
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18. Ataxic Guillain-Barré syndrome with anti-GQ1b antibody: relation to Miller Fisher syndrome.
- Author
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Yuki, N, Susuki, K, and Hirata, K
- Published
- 2000
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19. Encephalopathy in scleromyxedema.
- Author
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Johkura, K, Susuki, K, Hasegawa, O, Kuroiwa, Y, and Komatsumoto, S
- Published
- 1999
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20. Catatonia complicated by pneumothorax successfully treated with electroconvulsive therapy.
- Author
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Susuki K, Katsura M, Ebina Y, Takano T, and Matsuoka H
- Published
- 2007
21. Pharyngeal-brachial palsy after cytomegalovirus colitis.
- Author
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Pan, C-L, Shun, C-T, Susuki, K, Yuki, N, and Hsieh, S-T
- Published
- 2004
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22. Cerebral white matter lesions in acute motor axonal neuropathy.
- Author
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Sekiguchi, K, Susuki, K, Funakawa, I, Jinnai, K, and Yuki, N
- Published
- 2003
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- View/download PDF
23. Unilateral oculomotor nerve palsy associated with anti-GQ1b IgG antibody.
- Author
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Ichikawa, H, Kamiya, Y, Susuki, K, Suzuki, M, Yuki, N, and Kawamura, M
- Published
- 2002
- Full Text
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24. Ataxic form of Guillain-Barr syndrome associated with anti-GD1b IgG antibody.
- Author
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Yuki, N, Susuki, K, and Hirata, K
- Published
- 2000
25. Epidural compression of the cauda equina caused by vertebral osteoblastic metastasis of prostatic carcinoma: resolution by hormonal therapy.
- Author
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Susuki, K, Matsumoto, S, Kitagawa, N, Shinohara, H, Hasegawa, O, and Kuroiwa, Y
- Abstract
A 59 year old man with prostatic carcinoma developed epidural compression of the cauda equina caused by bony expansion from a vertebral osteoblastic metastasis. For medical reasons he could not undergo radiation or surgery. Hormonal therapy alone relieved his low back pain and restored ambulation and urinary function. Postmyelography CT showed that the bony expansion from the vertebra had completely disappeared after treatment. This is the first report of remarkable improvement due to hormonal therapy alone. [ABSTRACT FROM AUTHOR]
- Published
- 2000
26. 187 EFFICIENCY OF DIAGNOSIS OF CLINICAL AND SUBCLINICAL ENDOMETRITIS IN CATTLE EVALUATED BY HYSTEROSCOPY.
- Author
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Madoz, L. V., de la Sota, R. L, Susuki, K., Heuwieser, W., and Drillich, M.
- Subjects
DIAGNOSIS of endometrial diseases ,DIAGNOSIS ,HYSTEROSCOPY ,CYTOLOGY ,PALPATION ,PUERPERIUM ,HOLSTEIN-Friesian cattle ,DISEASES ,CATTLE diseases - Abstract
The objective of this study was to evaluate the efficiency of vaginoscopy and rectal palpation (palpable liquid in uterine horns) compared with hysteroscopy (presence of pus in the uterine lumen) for the diagnosis of clinical endometritis (CE), and hysteroscopy compared with endometrial cytology for the diagnosis of subclinical endometritis (SE) in postpartum dairy cows. Thirty Holstein cows between 20 and 35 days postpartum were examined for diagnosis of CE with a vaginal speculum, by rectal palpation, and by hysteroscopy; and examined for diagnosis of SE with hysteroscopy and endometrial cytology. Categorical data were analyzed with PROC CATMOD (SAS®, SAS Institute, Cary, NC, USA) and continuous data were analyzed with PROC GLM (SAS®, SAS Institute, Cary, NC, USA). Sensitivity, specificity, predicted value of a positive and negative result, and efficiency were calculated using Win Episcope®2.0 software (Clive, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK). Prevalence of CE diagnosed by vaginoscopy was 27%, by rectal palpation was 23%, and by hysteroscopy was 13%. When hysteroscopy, the only tool for direct examination of the endometrium, was used as the gold standard for diagnosis of CE, vaginoscopy had 100% sensitivity, 85% specificity, and 87% efficiency, and rectal palpation had 75% sensitivity, 85% specificity, and 83% efficiency. Prevalence of SE diagnosed by endometrial cytology was 35.3%. When endometrial cytology was used as the gold standard for diagnosis of SE, hysteroscopy had 11% sensitivity, 92% specificity, and 59% efficiency. In conclusion, vaginoscopy had higher sensitivity than, and similar specificity and efficiency to, rectal palpation for diagnosis of CE. Conversely, hysteroscopy, although having high specificity, had low sensitivity and efficiency for diagnosis of SE. Hysteroscopy proved to be efficient for diagnosis of CE but inefficient for diagnosis of SE. The authors gratefully acknowledge the support of the study by World of Medicine (WOM), Berlin, Germany, for providing all endoscopic equipment and the cooperation with the dairy farm in Brandenburg, Germany. Vanina Madoz visit to the Freie Universität Berlin was supported by a fellowship from the Deutscher Akademischer Austauschdienst, DAAD. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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27. Probe measurements of hydrogen fluxes during discharge cleaning in JFT-2M
- Author
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JFT-2M Team, Maeda, H., Susuki, K., Hasegawa, K., Honda, A., Ishibori, I., Kashiwa, Y., Kazawa, M., Kikuchi, K., Ohuchi, K., Okano, F., Sato, E., Shibata, T., Tani, T., Uno, S., Hoshino, K., Kasai, S., Kawakami, T., Kawashima, K., Matsuda, T., Matsumoto, H., Miura, Y., Mori, M., Nakazawa, I., Odajima, K., Ogawa, H., Ogawa, T., Ohasa, K., Ohtsuka, H., Sengoku, S., Shoji, T., Suzuki, N., Tamai, H., Uesugi, Y., Yamamoto, T., Yamauchi, T., and Matsuzaki, Y.
- Published
- 1989
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28. Tacrolimus induces fibroblast-to-myofibroblast transition via a TGF-β-dependent mechanism to contribute to renal fibrosis.
- Author
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Ume AC, Wenegieme TY, Shelby JN, Paul-Onyia CDB, Waite AMJ 3rd, Kamau JK, Adams DN, Susuki K, Bennett ES, Ren H, and Williams CR
- Subjects
- Animals, Mice, Actins metabolism, Calcineurin Inhibitors pharmacology, Fibroblasts metabolism, Fibrosis, Mice, Inbred C57BL, Receptors, Transforming Growth Factor beta metabolism, Myofibroblasts metabolism, Tacrolimus pharmacology, Transforming Growth Factor beta1 metabolism, Renal Insufficiency pathology
- Abstract
Use of immunosuppressant calcineurin inhibitors (CNIs) is limited by irreversible kidney damage, hallmarked by renal fibrosis. CNIs directly damage many renal cell types. Given the diverse renal cell populations, additional targeted cell types and signaling mechanisms warrant further investigation. We hypothesized that fibroblasts contribute to CNI-induced renal fibrosis and propagate profibrotic effects via the transforming growth factor-β (TGF-β)/Smad signaling axis. To test this, kidney damage-resistant mice (C57BL/6) received tacrolimus (10 mg/kg) or vehicle for 21 days. Renal damage markers and signaling mediators were assessed. To investigate their role in renal damage, mouse renal fibroblasts were exposed to tacrolimus (1 nM) or vehicle for 24 h. Morphological and functional changes in addition to downstream signaling events were assessed. Tacrolimus-treated kidneys displayed evidence of renal fibrosis. Moreover, α-smooth muscle actin expression was significantly increased, suggesting the presence of fibroblast activation. TGF-β receptor activation and downstream Smad2/3 signaling were also upregulated. Consistent with in vivo findings, tacrolimus-treated renal fibroblasts displayed a phenotypic switch known as fibroblast-to-myofibroblast transition (FMT), as α-smooth muscle actin, actin stress fibers, cell motility, and collagen type IV expression were significantly increased. These findings were accompanied by concomitant induction of TGF-β signaling. Pharmacological inhibition of the downstream TGF-β effector Smad3 attenuated tacrolimus-induced phenotypic changes. Collectively, these findings suggest that 1 ) tacrolimus inhibits the calcineurin/nuclear factor of activated T cells axis while inducing TGF-β1 ligand secretion and receptor activation in renal fibroblasts; 2 ) aberrant TGF-β receptor activation stimulates Smad-mediated production of myofibroblast markers, notable features of FMT; and 3 ) FMT contributes to extracellular matrix expansion in tacrolimus-induced renal fibrosis. These results incorporate renal fibroblasts into the growing list of CNI-targeted cell types and identify renal FMT as a process mediated via a TGF-β-dependent mechanism. NEW & NOTEWORTHY Renal fibrosis, a detrimental feature of irreversible kidney damage, remains a sinister consequence of long-term calcineurin inhibitor (CNI) immunosuppressive therapy. Our study not only incorporates renal fibroblasts into the growing list of cell types negatively impacted by CNIs but also identifies renal fibroblast-to-myofibroblast transition as a process mediated via a TGF-β-dependent mechanism. This insight will direct future studies investigating the feasibility of inhibiting TGF-β signaling to maintain CNI-mediated immunosuppression while ultimately preserving kidney health.
- Published
- 2023
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29. Distinct Changes in Calpain and Calpastatin during PNS Myelination and Demyelination in Rodent Models.
- Author
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Miller JA, Drouet DE, Yermakov LM, Elbasiouny MS, Bensabeur FZ, Bottomley M, and Susuki K
- Subjects
- Animals, Mice, Rats, Calpain metabolism, Calcium-Binding Proteins genetics, Calcium-Binding Proteins metabolism, Axons metabolism, Myelin Sheath metabolism, Sciatic Nerve metabolism, Rodentia metabolism, Demyelinating Diseases chemically induced, Demyelinating Diseases metabolism
- Abstract
Myelin forming around axons provides electrical insulation and ensures rapid and efficient transmission of electrical impulses. Disruptions to myelinated nerves often result in nerve conduction failure along with neurological symptoms and long-term disability. In the central nervous system, calpains, a family of calcium dependent cysteine proteases, have been shown to have a role in developmental myelination and in demyelinating diseases. The roles of calpains in myelination and demyelination in the peripheral nervous system remain unclear. Here, we show a transient increase of activated CAPN1, a major calpain isoform, in postnatal rat sciatic nerves when myelin is actively formed. Expression of the endogenous calpain inhibitor, calpastatin, showed a steady decrease throughout the period of peripheral nerve development. In the sciatic nerves of Trembler-J mice characterized by dysmyelination, expression levels of CAPN1 and calpastatin and calpain activity were significantly increased. In lysolecithin-induced acute demyelination in adult rat sciatic nerves, we show an increase of CAPN1 and decrease of calpastatin expression. These changes in the calpain-calpastatin system are distinct from those during central nervous system development or in acute axonal degeneration in peripheral nerves. Our results suggest that the calpain-calpastatin system has putative roles in myelination and demyelinating diseases of peripheral nerves.
- Published
- 2022
- Full Text
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30. The Type 2 Diabetes Factor Methylglyoxal Mediates Axon Initial Segment Shortening and Alters Neuronal Function at the Cellular and Network Levels.
- Author
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Griggs RB, Nguyen DVM, Yermakov LM, Jaber JM, Shelby JN, Steinbrunner JK, Miller JA, Gonzalez-Islas C, Wenner P, and Susuki K
- Subjects
- Animals, Female, Male, Mice, Neurons, Pyruvaldehyde, Axon Initial Segment, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2
- Abstract
Recent evidence suggests that alteration of axon initial segment (AIS) geometry (i.e., length or location along the axon) contributes to CNS dysfunction in neurological diseases. For example, AIS length is shorter in the prefrontal cortex of type 2 diabetic mice with cognitive impairment. To determine the key type 2 diabetes-related factor that produces AIS shortening we modified levels of insulin, glucose, or the reactive glucose metabolite methylglyoxal in cultures of dissociated cortices from male and female mice and quantified AIS geometry using immunofluorescent imaging of the AIS proteins AnkyrinG and βIV spectrin. Neither insulin nor glucose modification altered AIS length. Exposure to 100 but not 1 or 10 μm methylglyoxal for 24 h resulted in accumulation of the methylglyoxal-derived advanced glycation end-product hydroimidazolone and produced reversible AIS shortening without cell death. Methylglyoxal-evoked AIS shortening occurred in both excitatory and putative inhibitory neuron populations and in the presence of tetrodotoxin (TTX). In single-cell recordings resting membrane potential was depolarized at 0.5-3 h and returned to normal at 24 h. In multielectrode array (MEA) recordings methylglyoxal produced an immediate ∼300% increase in spiking and bursting rates that returned to normal within 2 min, followed by a ∼20% reduction of network activity at 0.5-3 h and restoration of activity to baseline levels at 24 h. AIS length was unchanged at 0.5-3 h despite the presence of depolarization and network activity reduction. Nevertheless, these results suggest that methylglyoxal could be a key mediator of AIS shortening and disruptor of neuronal function during type 2 diabetes., (Copyright © 2021 Griggs et al.)
- Published
- 2021
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31. TDP-43 maximizes nerve conduction velocity by repressing a cryptic exon for paranodal junction assembly in Schwann cells.
- Author
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Chang KJ, Agrawal I, Vainshtein A, Ho WY, Xin W, Tucker-Kellogg G, Susuki K, Peles E, Ling SC, and Chan JR
- Subjects
- Animals, DNA-Binding Proteins metabolism, Female, Male, Mice, DNA-Binding Proteins genetics, Exons, Intercellular Junctions metabolism, Neural Conduction, Schwann Cells metabolism
- Abstract
TDP-43 is extensively studied in neurons in physiological and pathological contexts. However, emerging evidence indicates that glial cells are also reliant on TDP-43 function. We demonstrate that deletion of TDP-43 in Schwann cells results in a dramatic delay in peripheral nerve conduction causing significant motor deficits in mice, which is directly attributed to the absence of paranodal axoglial junctions. By contrast, paranodes in the central nervous system are unaltered in oligodendrocytes lacking TDP-43. Mechanistically, TDP-43 binds directly to Neurofascin mRNA, encoding the cell adhesion molecule essential for paranode assembly and maintenance. Loss of TDP-43 triggers the retention of a previously unidentified cryptic exon, which targets Neurofascin mRNA for nonsense-mediated decay. Thus, TDP-43 is required for neurofascin expression, proper assembly and maintenance of paranodes, and rapid saltatory conduction. Our findings provide a framework and mechanism for how Schwann cell-autonomous dysfunction in nerve conduction is directly caused by TDP-43 loss-of-function., Competing Interests: KC, IA, AV, WH, WX, GT, KS, EP, SL, JC No competing interests declared, (© 2021, Chang et al.)
- Published
- 2021
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32. Precise Spatiotemporal Control of Nodal Na + Channel Clustering by Bone Morphogenetic Protein-1/Tolloid-like Proteinases.
- Author
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Eshed-Eisenbach Y, Devaux J, Vainshtein A, Golani O, Lee SJ, Feinberg K, Sukhanov N, Greenspan DS, Susuki K, Rasband MN, and Peles E
- Subjects
- Animals, Bone Morphogenetic Protein 1 metabolism, Mice, Mice, Knockout, Neural Conduction, Peripheral Nervous System, Protein Transport, Schwann Cells metabolism, Tolloid-Like Metalloproteinases metabolism, Bone Morphogenetic Protein 1 genetics, Cell Adhesion Molecules, Neuronal metabolism, Myelin Sheath metabolism, Ranvier's Nodes metabolism, Tolloid-Like Metalloproteinases genetics, Voltage-Gated Sodium Channels metabolism
- Abstract
During development of the peripheral nervous system (PNS), Schwann-cell-secreted gliomedin induces the clustering of Na
+ channels at the edges of each myelin segment to form nodes of Ranvier. Here we show that bone morphogenetic protein-1 (BMP1)/Tolloid (TLD)-like proteinases confine Na+ channel clustering to these sites by negatively regulating the activity of gliomedin. Eliminating the Bmp1/TLD cleavage site in gliomedin or treating myelinating cultures with a Bmp1/TLD inhibitor results in the formation of numerous ectopic Na+ channel clusters along axons that are devoid of myelin segments. Furthermore, genetic deletion of Bmp1 and Tll1 genes in mice using a Schwann-cell-specific Cre causes ectopic clustering of nodal proteins, premature formation of heminodes around early ensheathing Schwann cells, and altered nerve conduction during development. Our results demonstrate that by inactivating gliomedin, Bmp1/TLD functions as an additional regulatory mechanism to ensure the correct spatial and temporal assembly of PNS nodes of Ranvier., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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33. Impairment of cognitive flexibility in type 2 diabetic db/db mice.
- Author
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Yermakov LM, Griggs RB, Drouet DE, Sugimoto C, Williams MT, Vorhees CV, and Susuki K
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- Animals, Brain physiology, Cognition Disorders physiopathology, Diabetes Mellitus, Experimental metabolism, Diabetes Mellitus, Type 2 psychology, Disease Models, Animal, Executive Function physiology, Hippocampus physiology, Male, Maze Learning physiology, Memory Disorders physiopathology, Mice, Mice, Inbred Strains, Prefrontal Cortex physiology, Cognition physiology, Diabetes Mellitus, Experimental psychology, Memory, Short-Term physiology
- Abstract
Impaired executive function is a major peril for patients with type 2 diabetes, reducing quality of life and ability for diabetes management. Despite the significance of this impairment, few animal models of type 2 diabetes examine domains of executive function such as cognitive flexibility or working memory. Here, we evaluated these executive function domains in db/db mice, an established model of type 2 diabetes, at 10 and 24 weeks of age. The db/db mice showed impaired cognitive flexibility in the Morris water maze reversal phase. However, the db/db mice did not show apparent working memory disturbance in the spatial working memory version of the Morris water maze or in the radial water maze. We also examined axon initial segments (AIS) and nodes of Ranvier, key axonal domains for action potential initiation and propagation. AIS were significantly shortened in medial prefrontal cortex and hippocampus of 26-week-old db/db mice compared with controls, similar to our previous findings in 10-week-old mice. Nodes of Ranvier in corpus callosum, previously shown to be unchanged at 10 weeks, were elongated at 26 weeks, suggesting an important role for this domain in disease progression. Together, the findings help establish db/db mice as a model of impaired cognitive flexibility in type 2 diabetes and advance our understanding of its pathophysiology., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
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34. Methylglyoxal and a spinal TRPA1-AC1-Epac cascade facilitate pain in the db/db mouse model of type 2 diabetes.
- Author
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Griggs RB, Santos DF, Laird DE, Doolen S, Donahue RR, Wessel CR, Fu W, Sinha GP, Wang P, Zhou J, Brings S, Fleming T, Nawroth PP, Susuki K, and Taylor BK
- Subjects
- Animals, Avoidance Learning drug effects, Avoidance Learning physiology, Behavior, Animal drug effects, Behavior, Animal physiology, Cyclic AMP-Dependent Protein Kinases metabolism, Diabetes Mellitus, Type 2 complications, Male, Mice, Pain Measurement, Posterior Horn Cells drug effects, Posterior Horn Cells metabolism, Pyruvaldehyde pharmacology, Signal Transduction drug effects, Signal Transduction physiology, Adenylyl Cyclases metabolism, Diabetes Mellitus, Type 2 metabolism, Diabetic Neuropathies metabolism, Guanine Nucleotide Exchange Factors metabolism, Pyruvaldehyde metabolism, TRPA1 Cation Channel metabolism
- Abstract
Painful diabetic neuropathy (PDN) is a devastating neurological complication of diabetes. Methylglyoxal (MG) is a reactive metabolite whose elevation in the plasma corresponds to PDN in patients and pain-like behavior in rodent models of type 1 and type 2 diabetes. Here, we addressed the MG-related spinal mechanisms of PDN in type 2 diabetes using db/db mice, an established model of type 2 diabetes, and intrathecal injection of MG in conventional C57BL/6J mice. Administration of either a MG scavenger (GERP10) or a vector overexpressing glyoxalase 1, the catabolic enzyme for MG, attenuated heat hypersensitivity in db/db mice. In C57BL/6J mice, intrathecal administration of MG produced signs of both evoked (heat and mechanical hypersensitivity) and affective (conditioned place avoidance) pain. MG-induced Ca
2+ mobilization in lamina II dorsal horn neurons of C57BL/6J mice was exacerbated in db/db, suggestive of MG-evoked central sensitization. Pharmacological and/or genetic inhibition of transient receptor potential ankyrin subtype 1 (TRPA1), adenylyl cyclase type 1 (AC1), protein kinase A (PKA), or exchange protein directly activated by cyclic adenosine monophosphate (Epac) blocked MG-evoked hypersensitivity in C57BL/6J mice. Similarly, intrathecal administration of GERP10, or inhibitors of TRPA1 (HC030031), AC1 (NB001), or Epac (HJC-0197) attenuated hypersensitivity in db/db mice. We conclude that MG and sensitization of a spinal TRPA1-AC1-Epac signaling cascade facilitate PDN in db/db mice. Our results warrant clinical investigation of MG scavengers, glyoxalase inducers, and spinally-directed pharmacological inhibitors of a MG-TRPA1-AC1-Epac pathway for the treatment of PDN in type 2 diabetes., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2019
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35. Functional Domains in Myelinated Axons.
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Yermakov LM, Hong LA, Drouet DE, Griggs RB, and Susuki K
- Subjects
- Axons pathology, Humans, Nerve Fibers, Myelinated pathology, Neuroglia pathology, Neuroglia physiology, Axons physiology, Nerve Fibers, Myelinated physiology, Neural Conduction
- Abstract
Propagation of action potentials along axons is optimized through interactions between neurons and myelinating glial cells. Myelination drives division of the axons into distinct molecular domains including nodes of Ranvier. The high density of voltage-gated sodium channels at nodes generates action potentials allowing for rapid and efficient saltatory nerve conduction. At paranodes flanking both sides of the nodes, myelinating glial cells interact with axons, forming junctions that are essential for node formation and maintenance. Recent studies indicate that the disruption of these specialized axonal domains is involved in the pathophysiology of various neurological diseases. Loss of paranodal axoglial junctions due to genetic mutations or autoimmune attack against the paranodal proteins leads to nerve conduction failure and neurological symptoms. Breakdown of nodal and paranodal proteins by calpains, the calcium-dependent cysteine proteases, may be a common mechanism involved in various nervous system diseases and injuries. This chapter reviews recent progress in neurobiology and pathophysiology of specialized axonal domains along myelinated nerve fibers.
- Published
- 2019
- Full Text
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36. Glial βII Spectrin Contributes to Paranode Formation and Maintenance.
- Author
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Susuki K, Zollinger DR, Chang KJ, Zhang C, Huang CY, Tsai CR, Galiano MR, Liu Y, Benusa SD, Yermakov LM, Griggs RB, Dupree JL, and Rasband MN
- Subjects
- Animals, Female, Male, Mice, Mice, Knockout, Ranvier's Nodes, Axons metabolism, Cytoskeleton metabolism, Neuroglia metabolism, Spectrin metabolism
- Abstract
Action potential conduction along myelinated axons depends on high densities of voltage-gated Na
+ channels at the nodes of Ranvier. Flanking each node, paranodal junctions (paranodes) are formed between axons and Schwann cells in the peripheral nervous system (PNS) or oligodendrocytes in the CNS. Paranodal junctions contribute to both node assembly and maintenance. Despite their importance, the molecular mechanisms responsible for paranode assembly and maintenance remain poorly understood. βII spectrin is expressed in diverse cells and is an essential part of the submembranous cytoskeleton. Here, we show that Schwann cell βII spectrin is highly enriched at paranodes. To elucidate the roles of glial βII spectrin, we generated mutant mice lacking βII spectrin in myelinating glial cells by crossing mice with a floxed allele of Sptbn1 with Cnp-Cre mice, and analyzed both male and female mice. Juvenile (4 weeks) and middle-aged (60 weeks) mutant mice showed reduced grip strength and sciatic nerve conduction slowing, whereas no phenotype was observed between 8 and 24 weeks of age. Consistent with these findings, immunofluorescence microscopy revealed disorganized paranodes in the PNS and CNS of both postnatal day 13 and middle-aged mutant mice, but not in young adult mutant mice. Electron microscopy confirmed partial loss of transverse bands at the paranodal axoglial junction in the middle-aged mutant mice in both the PNS and CNS. These findings demonstrate that a spectrin-based cytoskeleton in myelinating glia contributes to formation and maintenance of paranodal junctions. SIGNIFICANCE STATEMENT Myelinating glia form paranodal axoglial junctions that flank both sides of the nodes of Ranvier. These junctions contribute to node formation and maintenance and are essential for proper nervous system function. We found that a submembranous spectrin cytoskeleton is highly enriched at paranodes in Schwann cells. Ablation of βII spectrin in myelinating glial cells disrupted the paranodal cell adhesion complex in both peripheral and CNSs, resulting in muscle weakness and sciatic nerve conduction slowing in juvenile and middle-aged mice. Our data show that a spectrin-based submembranous cytoskeleton in myelinating glia plays important roles in paranode formation and maintenance., (Copyright © 2018 the authors 0270-6474/18/386063-13$15.00/0.)- Published
- 2018
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37. Type 2 Diabetes Leads to Axon Initial Segment Shortening in db/db Mice.
- Author
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Yermakov LM, Drouet DE, Griggs RB, Elased KM, and Susuki K
- Abstract
Cognitive and mood impairments are common central nervous system complications of type 2 diabetes, although the neuronal mechanism(s) remains elusive. Previous studies focused mainly on neuronal inputs such as altered synaptic plasticity. Axon initial segment (AIS) is a specialized functional domain within neurons that regulates neuronal outputs. Structural changes of AIS have been implicated as a key pathophysiological event in various psychiatric and neurological disorders. Here we evaluated the structural integrity of the AIS in brains of db/db mice, an established animal model of type 2 diabetes associated with cognitive and mood impairments. We assessed the AIS before (5 weeks of age) and after (10 weeks) the development of type 2 diabetes, and after daily exercise treatment of diabetic condition. We found that the development of type 2 diabetes is associated with significant AIS shortening in both medial prefrontal cortex and hippocampus, as evident by immunostaining of the AIS structural protein βIV spectrin. AIS shortening occurs in the absence of altered neuronal and AIS protein levels. We found no change in nodes of Ranvier, another neuronal functional domain sharing a molecular organization similar to the AIS. This is the first study to identify AIS alteration in type 2 diabetes condition. Since AIS shortening is known to lower neuronal excitability, our results may provide a new avenue for understanding and treating cognitive and mood impairments in type 2 diabetes.
- Published
- 2018
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38. Methylglyoxal Disrupts Paranodal Axoglial Junctions via Calpain Activation.
- Author
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Griggs RB, Yermakov LM, Drouet DE, Nguyen DVM, and Susuki K
- Subjects
- Animals, Axons metabolism, Cytoskeletal Proteins metabolism, Dipeptides pharmacology, Dose-Response Relationship, Drug, Female, Gene Expression Regulation drug effects, In Vitro Techniques, Male, Membrane Proteins metabolism, Membrane Proteins pharmacology, Mice, Mice, Inbred C57BL, Muscle Proteins metabolism, Neuroglia metabolism, Optic Nerve cytology, Pan paniscus metabolism, Phosphate Transport Proteins metabolism, Sciatic Nerve cytology, Zonula Occludens-1 Protein metabolism, Axons drug effects, Calpain metabolism, Neuroeffector Junction drug effects, Neuroglia drug effects, Pyruvaldehyde pharmacology, Ranvier's Nodes drug effects
- Abstract
Nodes of Ranvier and associated paranodal and juxtaparanodal domains along myelinated axons are essential for normal function of the peripheral and central nervous systems. Disruption of these domains as well as increases in the reactive carbonyl species methylglyoxal are implicated as a pathophysiology common to a wide variety of neurological diseases. Here, using an ex vivo nerve exposure model, we show that increasing methylglyoxal produces paranodal disruption, evidenced by disorganized immunostaining of axoglial cell-adhesion proteins, in both sciatic and optic nerves from wild-type mice. Consistent with previous studies showing that increase of methylglyoxal can alter intracellular calcium homeostasis, we found upregulated activity of the calcium-activated protease calpain in sciatic nerves after methylglyoxal exposure. Methylglyoxal exposure altered clusters of proteins that are known as calpain substrates: ezrin in Schwann cell microvilli at the perinodal area and zonula occludens 1 in Schwann cell autotypic junctions at paranodes. Finally, treatment with the calpain inhibitor calpeptin ameliorated methylglyoxal-evoked ezrin loss and paranodal disruption in both sciatic and optic nerves. Our findings strongly suggest that elevated methylglyoxal levels and subsequent calpain activation contribute to the disruption of specialized axoglial domains along myelinated nerve fibers in neurological diseases.
- Published
- 2018
- Full Text
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39. Comparative anatomy of the dorsal hump in mature Pacific salmon.
- Author
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Susuki K, Ban M, Ichimura M, and Kudo H
- Subjects
- Animals, Fish Proteins metabolism, Japan, Lipids analysis, Male, Oncorhynchus keta anatomy & histology, Salmon anatomy & histology, Water analysis, Anatomy, Comparative, Oncorhynchus anatomy & histology, Sexual Maturation
- Abstract
Mature male Pacific salmon (Genus Oncorhynchus) demonstrate prominent morphological changes, such as the development of a dorsal hump. The degree of dorsal hump formation depends on the species in Pacific salmon. It is generally accepted that mature males of sockeye (O. nerka) and pink (O. gorbuscha) salmon develop most pronounced dorsal humps. The internal structure of the dorsal hump in pink salmon has been confirmed in detail. In this study, the dorsal hump morphologies were analyzed in four Pacific salmon species inhabiting Japan, masu (O. masou), sockeye, chum (O. keta), and pink salmon. The internal structure of the dorsal humps also depended on the species; sockeye and pink salmon showed conspicuous development of connective tissue and growth of bone tissues in the dorsal tissues. Masu and chum salmon exhibited less-pronounced increases in connective tissues and bone growth. Hyaluronic acid was clearly detected in dorsal hump connective tissue by histochemistry, except for in masu salmon. The lipid content in dorsal hump connective tissue was richer in masu and chum salmon than in sockeye and pink salmon. These results revealed that the patterns of dorsal hump formation differed among species, and especially sockeye and pink salmon develop pronounced dorsal humps through both increases in the amount of connective tissue and the growth of bone tissues. In contrast, masu and chum salmon develop their dorsal humps by the growth of bone tissues, rather than the development of connective tissue., (© 2017 Wiley Periodicals, Inc.)
- Published
- 2017
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- View/download PDF
40. Thickness control of 3-dimensional mesoporous silica ultrathin films by wet-etching.
- Author
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Kobayashi M, Susuki K, Otani T, Enomoto S, Otsuji H, Kuroda Y, Wada H, Shimojima A, Homma T, and Kuroda K
- Abstract
The thickness of 3-dimensional (3D) mesoporous silica ultrathin films was controlled at a single-nanometer scale by wet-etching. A drop casting method with an aqueous etchant of ammonium fluoride was effective in etching the surfaces of films in the direction perpendicular to their substrates. The decrease in the film thickness depends on the interface tension of etching solutions. The wettability of thin films also influences the etching. CoPt nanodots were electrodeposited within ultrathin silica films on Ru substrates to form CoPt nanodot patterns.
- Published
- 2017
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41. Chronic peripheral nerve compression disrupts paranodal axoglial junctions.
- Author
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Otani Y, Yermakov LM, Dupree JL, and Susuki K
- Subjects
- Animals, Ankyrins metabolism, Cell Adhesion Molecules, Neuronal metabolism, Disease Models, Animal, Female, Functional Laterality, Gene Expression Regulation, Mice, Mice, Inbred C57BL, Microscopy, Electron, Transmission, Nerve Growth Factors metabolism, Neural Conduction physiology, Ranvier's Nodes pathology, Ranvier's Nodes ultrastructure, Sciatic Nerve pathology, Sciatic Nerve physiopathology, Sciatic Nerve ultrastructure, Shab Potassium Channels metabolism, Arthrogryposis pathology, Arthrogryposis physiopathology, Cell Adhesion Molecules metabolism, Evoked Potentials, Motor physiology, Hereditary Sensory and Motor Neuropathy pathology, Hereditary Sensory and Motor Neuropathy physiopathology, Ranvier's Nodes metabolism
- Abstract
Introduction: Peripheral nerves are often exposed to mechanical stress leading to compression neuropathies. The pathophysiology underlying nerve dysfunction by chronic compression is largely unknown., Methods: We analyzed molecular organization and fine structures at and near nodes of Ranvier in a compression neuropathy model in which a silastic tube was placed around the mouse sciatic nerve., Results: Immunofluorescence study showed that clusters of cell adhesion complex forming paranodal axoglial junctions were dispersed and overlapped frequently with juxtaparanodal components. These paranodal changes occurred without internodal myelin damage. The distribution and pattern of paranodal disruption suggests that these changes are the direct result of mechanical stress. Electron microscopy confirmed loss of paranodal axoglial junctions., Conclusions: Our data show that chronic nerve compression disrupts paranodal junctions and axonal domains required for proper peripheral nerve function. These results provide important clues toward better understanding of the pathophysiology underlying nerve dysfunction in compression neuropathies. Muscle Nerve 55: 544-554, 2017., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2017
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42. Direct Observation of the Outermost Surfaces of Mesoporous Silica Thin Films by High Resolution Ultralow Voltage Scanning Electron Microscopy.
- Author
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Kobayashi M, Susuki K, Otsuji H, Sakuda Y, Asahina S, Kikuchi N, Kanazawa T, Kuroda Y, Wada H, Shimojima A, and Kuroda K
- Abstract
The properties of the outermost surfaces of mesoporous silica thin films are critical in determining their functions. Obtaining information on the presence or absence of silica layers on the film surfaces and on the degree of mesopore opening is essential for applications of surface mesopores. In this study, the outermost surfaces of mesoporous silica thin films with 3-dimensional orthorhombic and 2-dimensional hexagonal structures were observed using ultralow voltage high resolution scanning electron microscopy (HR-SEM) with decelerating optics. SEM images of the surfaces before and after etching with NH
4 F were taken at various landing voltages. Comparing the images taken under different conditions indicated that the outermost surfaces of the nonetched mesoporous silica thin films are coated with a thin layer of silica. The images taken at an ultralow landing voltage (i.e., 80 V) showed that the presence or absence of surface silica layers depends on whether the film was etched with an aqueous solution of NH4 F. The mesostructures of both the etched and nonetched films were visible in images taken at a conventional landing voltage (2 kV); hence, the ultralow landing voltage was more suitable for analyzing the outermost surfaces. The SEM observations provided detailed information about the surfaces of mesoporous silica thin films, such as the degree of pore opening and their homogeneities. AFM images of nonetched 2-dimensional hexagonal mesoporous silica thin films show that the shape of the silica layer on the surface of the films reflects the curvature of the top surface of the cylindrical mesochannels. SEM images taken at various landing voltages are discussed, with respect to the electron penetration range at each voltage. This study increases our understanding of the surfaces of mesoporous silica thin films, which may lead to potential applications utilizing the periodically arranged mesopores on these surfaces.- Published
- 2017
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43. Formation and disruption of functional domains in myelinated CNS axons.
- Author
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Griggs RB, Yermakov LM, and Susuki K
- Subjects
- Action Potentials, Alzheimer Disease metabolism, Alzheimer Disease pathology, Animals, Brain Injuries metabolism, Brain Injuries pathology, Calpain metabolism, Humans, Mitochondria metabolism, Multiple Sclerosis metabolism, Multiple Sclerosis pathology, Ranvier's Nodes physiology, Axons physiology, Central Nervous System metabolism, Myelin Sheath physiology
- Abstract
Communication in the central nervous system (CNS) occurs through initiation and propagation of action potentials at excitable domains along axons. Action potentials generated at the axon initial segment (AIS) are regenerated at nodes of Ranvier through the process of saltatory conduction. Proper formation and maintenance of the molecular structure at the AIS and nodes are required for sustaining conduction fidelity. In myelinated CNS axons, paranodal junctions between the axolemma and myelinating oligodendrocytes delineate nodes of Ranvier and regulate the distribution and localization of specialized functional elements, such as voltage-gated sodium channels and mitochondria. Disruption of excitable domains and altered distribution of functional elements in CNS axons is associated with demyelinating diseases such as multiple sclerosis, and is likely a mechanism common to other neurological disorders. This review will provide a brief overview of the molecular structure of the AIS and nodes of Ranvier, as well as the distribution of mitochondria in myelinated axons. In addition, this review highlights important structural and functional changes within myelinated CNS axons that are associated with neurological dysfunction., (Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.)
- Published
- 2017
- Full Text
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44. Submembranous cytoskeletons stabilize nodes of Ranvier.
- Author
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Susuki K, Otani Y, and Rasband MN
- Subjects
- Animals, Ankyrins metabolism, Gap Junctions metabolism, Humans, Ion Channels physiology, Spectrin metabolism, Cell Membrane metabolism, Cytoskeleton metabolism, Ranvier's Nodes physiology
- Abstract
Rapid action potential propagation along myelinated axons requires voltage-gated Na(+) (Nav) channel clustering at nodes of Ranvier. At paranodes flanking nodes, myelinating glial cells interact with axons to form junctions. The regions next to the paranodes called juxtaparanodes are characterized by high concentrations of voltage-gated K(+) channels. Paranodal axoglial junctions function as barriers to restrict the position of these ion channels. These specialized domains along the myelinated nerve fiber are formed by multiple molecular mechanisms including interactions between extracellular matrix, cell adhesion molecules, and cytoskeletal scaffolds. This review highlights recent findings into the roles of submembranous cytoskeletal proteins in the stabilization of molecular complexes at and near nodes. Axonal ankyrin-spectrin complexes stabilize Nav channels at nodes. Axonal protein 4.1B-spectrin complexes contribute to paranode and juxtaparanode organization. Glial ankyrins enriched at paranodes facilitate node formation. Finally, disruption of spectrins or ankyrins by genetic mutations or proteolysis is involved in the pathophysiology of various neurological or psychiatric disorders., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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45. Activity-dependent regulation of excitable axonal domains.
- Author
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Susuki K and Kuba H
- Subjects
- Animals, Myelin Sheath physiology, Neuroglia physiology, Neuronal Plasticity physiology, Action Potentials physiology, Axons physiology
- Abstract
Rapid action potential propagation along myelinated axons requires voltage-gated Na(+) channel clustering at the axon initial segments (AISs) and nodes of Ranvier. The AIS is intrinsically defined by cytoskeletal proteins expressed in axons, whereas nodes of Ranvier are formed by interaction between neurons and myelinating glia. These axonal domains have long been considered stable structures, but recent studies revealed that they are plastic and contribute to fine adjustment of neuronal activities and circuit function. The AIS changes its distribution and maintains neural circuit activity at a constant level. Morphological changes in myelinated nerve structures presumably modulate the excitability of nodal regions and regulate the timing of activity, thereby optimizing signal processing in a neural circuit. This review highlights recent findings on the structural plasticity of these excitable axonal domains.
- Published
- 2016
- Full Text
- View/download PDF
46. Sialylation regulates brain structure and function.
- Author
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Yoo SW, Motari MG, Susuki K, Prendergast J, Mountney A, Hurtado A, and Schnaar RL
- Subjects
- Animals, Astrocytes metabolism, Behavior, Animal physiology, Demyelinating Diseases genetics, Demyelinating Diseases metabolism, Demyelinating Diseases pathology, Gangliosides metabolism, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Mutant Strains, Microglia metabolism, Models, Animal, Mutant Proteins genetics, Mutant Proteins metabolism, Nerve Tissue Proteins metabolism, Neurons metabolism, Sialoglycoproteins metabolism, Sialyltransferases metabolism, beta-Galactoside alpha-2,3-Sialyltransferase, Brain anatomy & histology, Brain metabolism, Sialic Acids metabolism, Sialyltransferases deficiency, Sialyltransferases genetics
- Abstract
Every cell expresses a molecularly diverse surface glycan coat (glycocalyx) comprising its interface with its cellular environment. In vertebrates, the terminal sugars of the glycocalyx are often sialic acids, 9-carbon backbone anionic sugars implicated in intermolecular and intercellular interactions. The vertebrate brain is particularly enriched in sialic acid-containing glycolipids termed gangliosides. Human congenital disorders of ganglioside biosynthesis result in paraplegia, epilepsy, and intellectual disability. To better understand sialoglycan functions in the nervous system, we studied brain anatomy, histology, biochemistry, and behavior in mice with engineered mutations in St3gal2 and St3gal3, sialyltransferase genes responsible for terminal sialylation of gangliosides and some glycoproteins. St3gal2/3 double-null mice displayed dysmyelination marked by a 40% reduction in major myelin proteins, 30% fewer myelinated axons, a 33% decrease in myelin thickness, and molecular disruptions at nodes of Ranvier. In part, these changes may be due to dysregulation of ganglioside-mediated oligodendroglial precursor cell proliferation. Neuronal markers were also reduced up to 40%, and hippocampal neurons had smaller dendritic arbors. Young adult St3gal2/3 double-null mice displayed impaired motor coordination, disturbed gait, and profound cognitive disability. Comparisons among sialyltransferase mutant mice provide insights into the functional roles of brain gangliosides and sialoglycoproteins consistent with related human congenital disorders., (© FASEB.)
- Published
- 2015
- Full Text
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47. Glial ankyrins facilitate paranodal axoglial junction assembly.
- Author
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Chang KJ, Zollinger DR, Susuki K, Sherman DL, Makara MA, Brophy PJ, Cooper EC, Bennett V, Mohler PJ, and Rasband MN
- Subjects
- Animals, Ankyrins analysis, Ankyrins genetics, Axons chemistry, Cells, Cultured, Mice, Mice, Inbred C57BL, Mice, Knockout, Neuroglia chemistry, Oligodendroglia chemistry, Rats, Sprague-Dawley, Ankyrins biosynthesis, Axons metabolism, Neuroglia metabolism, Oligodendroglia metabolism
- Abstract
Neuron-glia interactions establish functional membrane domains along myelinated axons. These include nodes of Ranvier, paranodal axoglial junctions and juxtaparanodes. Paranodal junctions are the largest vertebrate junctional adhesion complex, and they are essential for rapid saltatory conduction and contribute to assembly and maintenance of nodes. However, the molecular mechanisms underlying paranodal junction assembly are poorly understood. Ankyrins are cytoskeletal scaffolds traditionally associated with Na(+) channel clustering in neurons and are important for membrane domain establishment and maintenance in many cell types. Here we show that ankyrin-B, expressed by Schwann cells, and ankyrin-G, expressed by oligodendrocytes, are highly enriched at the glial side of paranodal junctions where they interact with the essential glial junctional component neurofascin 155. Conditional knockout of ankyrins in oligodendrocytes disrupts paranodal junction assembly and delays nerve conduction during early development in mice. Thus, glial ankyrins function as major scaffolds that facilitate early and efficient paranodal junction assembly in the developing CNS.
- Published
- 2014
- Full Text
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48. Dorsal hump morphology in pink salmon (Oncorhynchus gorbuscha).
- Author
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Susuki K, Ichimura M, Koshino Y, Kaeriyama M, Takagi Y, Adachi S, and Kudo H
- Subjects
- Animals, Bone and Bones physiology, Cartilage chemistry, Collagen analysis, Connective Tissue chemistry, Male, Salmon physiology, Sexual Maturation, Water analysis, Salmon anatomy & histology
- Abstract
Mature male Pacific salmon (Genus Oncorhynchus) develop a dorsal hump, as a secondary male sexual characteristic, during the spawning period. Previous gross anatomical studies have indicated that the dorsal humps of salmon are mainly composed of cartilaginous tissue (Davidson [1935] J Morphol 57:169-183.) However, the histological and biochemical characteristics of such humps are poorly understood. In this study, the detailed microstructures and components of the dorsal humps of pink salmon were analyzed using histochemical techniques and electrophoresis. In mature males, free interneural spines and neural spines were located in a line near to the median septum of the dorsal hump. No cartilaginous tissue was detected within the dorsal hump. Fibrous and mucous connective tissues were mainly found in three regions of the dorsal hump: i) the median septum, ii) the distal region, and iii) the crescent-shaped region. Both the median septum and distal region consisted of connective tissue with a high water content, which contained elastic fibers and hyaluronic acid. It was also demonstrated that the lipid content of the dorsal hump connective tissue was markedly decreased in the mature males compared with the immature and maturing males. Although, the crescent-shaped region of the hump consisted of connective tissue, it did not contain elastic fibers, hyaluronic acid, or lipids. In an ultrastructural examination, it was found that all of the connective tissues in the dorsal hump were composed of collagen fibers. Gel electrophoresis of collagen extracts from these tissues found that the collagen in the dorsal hump is composed of Type I collagen, as is the case in salmon skin. These results indicate that in male pink salmon the dorsal hump is formed as a result of an increase in the amount of connective tissue, rather than cartilage, and the growth of free interneural spines and neural spines., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2014
- Full Text
- View/download PDF
49. Membrane domain organization of myelinated axons requires βII spectrin.
- Author
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Zhang C, Susuki K, Zollinger DR, Dupree JL, and Rasband MN
- Subjects
- Animals, Carrier Proteins genetics, Cell Adhesion Molecules, Neuronal, Cell Membrane, Cells, Cultured, Mice, Mice, Knockout, Microfilament Proteins genetics, Myelin Sheath metabolism, Nerve Tissue Proteins metabolism, Ranvier's Nodes, Axons metabolism, Carrier Proteins metabolism, Microfilament Proteins metabolism, Nerve Fibers, Myelinated metabolism, Potassium Channels physiology
- Abstract
The precise and remarkable subdivision of myelinated axons into molecularly and functionally distinct membrane domains depends on axoglial junctions that function as barriers. However, the molecular basis of these barriers remains poorly understood. Here, we report that genetic ablation and loss of axonal βII spectrin eradicated the paranodal barrier that normally separates juxtaparanodal K(+) channel protein complexes located beneath the myelin sheath from Na(+) channels located at nodes of Ranvier. Surprisingly, the K(+) channels and their associated proteins redistributed into paranodes where they colocalized with intact Caspr-labeled axoglial junctions. Furthermore, electron microscopic analysis of the junctions showed intact paranodal septate-like junctions. Thus, the paranodal spectrin-based submembranous cytoskeleton comprises the paranodal barriers required for myelinated axon domain organization.
- Published
- 2013
- Full Text
- View/download PDF
50. Nodo-paranodopathy: beyond the demyelinating and axonal classification in anti-ganglioside antibody-mediated neuropathies.
- Author
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Uncini A, Susuki K, and Yuki N
- Subjects
- Animals, Axons immunology, Disease Models, Animal, Guillain-Barre Syndrome immunology, Humans, Neural Conduction immunology, Autoantibodies immunology, Gangliosides immunology, Polyneuropathies immunology, Ranvier's Nodes immunology
- Abstract
In some anti-ganglioside antibody-mediated neuropathies, human and experimental data suggest a common pathogenic mechanism of dysfunction/disruption at the node of Ranvier resulting in a pathophysiologic continuum from transitory nerve conduction failure to axonal degeneration. The traditional classification of polyneuropathies into demyelinating or axonal may generate some confusion in the electrophysiological diagnosis of Guillain-Barré syndrome subtypes associated with anti-ganglioside antibodies. The axonal forms show, besides axonal degeneration, promptly reversible nerve conduction failure. This may be interpreted, by a single electrophysiological study, as demyelinating conduction block or distal axonal degeneration leading to errors in classification and in establishing prognosis. Moreover the term axonal may be misleading as it is commonly associated to axonal degeneration and not to a transitory, promptly reversible, dysfunction of the excitable axolemma. To focus on the site of nerve injury and overcome the classification difficulties, we propose the new category of nodo-paranodopathy which seems appropriate to various acute and chronic neuropathies associated with anti-ganglioside antibodies and we think better systematizes the neuropathies characterized by an autoimmune attack targeting the nodal region., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
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