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Growth associated protein 43 and neurofilament immunolabeling in the transected lumbar spinal cord of lizard indicates limited axonal regeneration

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Neural Regeneration Research 2022年第5期17卷 1034-1041页

作者： Lorenzo Alibardi Comparative Histolab Padova and Department of Biology University of BolognaBolognaItaly

Previous cytological studies on the transected lumbar spinal cord of lizards have shown the presence of differentiating glial cells,few neurons and axons in the bridge region between the proximal and distal stumps of the spinal cord in some cases.A limited number of axons(20-50)can cross the bridge and re-connect the caudal stump of the spinal cord with small neurons located in the rostral stump of the spinal cord.This axonal regeneration appears to be related to the recovery of hind-limb movements after initial paralysis.The present study extends previous studies and shows that after transection of the lumbar spinal cord in lizards,a glial-connective tissue bridge that reconnects the rostral and caudal stumps of the interrupted spinal cord is formed at 11-34 days post-injury.Following an initial paralysis some recovery of hindlimb movements occurs within 1-3 months post-injury.Immunohistochemical and ultrastructural analysis for a growth associated protein 43(GAP-43)of 48-50 k Da shows that sparse GAP-43 positive axons are present in the proximal stump of the spinal cord but their number decreased in the bridge at 11-34 days post-transection.Few immunolabeled axons with a neurofilament protein of 200-220 k Da were seen in the bridge at 11-22 days post-transection but their number increased at 34 days and 3 months post-amputation in lizards that have recovered some hindlimb movements.Numerous neurons in the rostral and caudal stumps of the spinal cord were also labeled for GAP43,a cytoplasmic protein that is trans-located into their axonal growth cones.This indicates that GAP-43 biosynthesis is related to axonal regeneration and sprouting from neurons that were damaged by the transection.Taken together,previous studies that utilized tract-tracing technique to label the present observations confirm that a limited axonal re-connection of the transected spinal cord occurs 1-3 months post-injury in lizards.The few regenerating-sprouting axons within the bridge reconnect the caudal with the rostral stumps of the spina

关键词： GAP-43 immunocytochemistry lizard neurofilaments regeneration spinal cord

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Assembly and structure of neurofilaments isolated from bovine spinal cord

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Science China(Life Sciences) 1999年第3期42卷 233-239页

作者：佟向军陈建国刘洁庞世瑾翟中和

neurofilaments (NFs) are neuron-specific intermediate filaments. The NFs were isolated from bovine spinal cord by differential centrifugation. The NFs were detected with electron microscopy and scanning tunneling microscopy (STM). Under STM, two kinds of sidearm of NFs were revealed: one was short, the other was long. They were arrayed along the 10-nm width core filaments one by one. The intervals between two adjacent long sidearms or two short sidearms were 20—22 nm, while those between two adjacent long and short sidearms were 10—11 nm. It was proposed that the rod domain of NF triplet prnteins was 3/4-staggered. The assembly properties of NF triplet proteins were also studied. Immuno-colloidal-gold labeling assay showed that NF-M and NF-H are able to co-assemble into long filaments with NF-L. NF-M and NF-H can also co-constitute into winding filaments.

关键词： neurofilaments (NFs) STM sidearm structure assembly immunogold.

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Effects of estrogen receptor modulators on cytoskeletal proteins in the central nervous system

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Neural Regeneration Research 2017年第8期12卷 1231-1240页

作者： Julia J.Segura-Uribe Rodolfo Pinto-Almazán Angélica Coyoy-Salgado Claudia E.Fuentes-Venado Christian Guerra-Araiza Unidad de Investigacion Modica en Enfermedades Neurologicas Hospital de Especialidades Centro Medico Nacional Siglo XXI Instituto Mexicano del Seguro Social Mexico City Mexico Seccion de Estudios de Posgrado e Investigacion Escuela Superior de Medicina Instituto Politecnico Nacional Mexico City Mexico Unidad de Investigacion Hospital Regional de Alta Especialidad Ixtapaluca Ixtapaluca Mexico Institute for the Developing Mind Children's Hospital Los Angeles Los Angeles CA USA Department of Pediatrics Keck School of Medicine University of Southern California Los Angeles CA USA Consejo Nacional de Ciencia y Tecnologia Mexico City Mexico Clinica de Trastornos del Sueno Universidad Autonoma Metropolitana-Iztapalapa Mexico City Mexico Servicio de Medicina Fisica y Rehabilitacion Hospital General de Zona No. 197 Texcoco Mexico Unidad de Investigacion Modica en Farmacologla Hospital de Especialidades Centro Medico Nacional Siglo XXI Instituto Mexicano del Seguro Social Mexico City Mexico

Estrogen receptor modulators are compounds of interest because of their estrogenic agonistic/antagonistic effects and tissue specificity. These compounds have many clinical applications, particularly for breast cancer treatment and osteoporosis in postmenopausal women, as well as for the treatment of climacteric symptoms. Similar to estrogens, neuroprotective effects of estrogen receptor modulators have been described in different models. However, the mechanisms of action of these compounds in the central nervous system have not been fully described. We conducted a systematic search to investigate the effects of estrogen receptor modulators in the central nervous system, focusing on the modulation of cytoskeletal proteins. We found that raloxifene, tamoxifen, and tibolone modulate some cytoskeletal proteins such as tau, microtuble-associated protein 1（MAP1）, MAP2, neurofilament 38（NF38） by different mechanisms of action and at different levels： neuronal microfilaments, intermediate filaments, and microtubule-associated proteins. Finally, we emphasize the importance of the study of these compounds in the treatment of neurodegenerative diseases since they present the benefits of estrogens without their side effects.

关键词： estrogen receptor modulators selective estrogen receptor modulators microtubules neurofilaments tibolone tamoxifen raloxifene

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Detecting neurodegenerative pathology in multiple sclerosis before irreversible brain tissue loss sets in

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Translational Neurodegeneration 2019年第1期8卷 466-482页

作者： Jeroen Van Schependom Kaat Guldolf Marie Béatrice D’hooghe Guy Nagels Miguel D’haeseleer Neurology Department Universitair Ziekenhuis BrusselCenter for NeurosciencesVrije Universiteit BrusselLaarbeeklaan 1011090 BrusselBelgium Radiology Department Universitair Ziekenhuis Brussel BrusselsBelgium Nationaal Multiple Sclerose Centrum MelsbroekBelgium

Background:Multiple sclerosis(MS)is a complex chronic inflammatory and degenerative disorder of the central nervous system.Accelerated brain volume loss,or also termed atrophy,is currently emerging as a popular imaging marker of neurodegeneration in affected patients,but,unfortunately,can only be reliably interpreted at the time when irreversible tissue damage likely has already occurred.Timing of treatment decisions based on brain atrophy may therefore be viewed as suboptimal.Main body:This Narrative Review focuses on alternative techniques with the potential of detecting neurodegenerative events in the brain of subjects with MS prior to the atrophic stage.First,metabolic and molecular imaging provide the opportunity to identify early subcellular changes associated with energy dysfunction,which is an assumed core mechanism of axonal degeneration in MS.Second,cerebral hypoperfusion has been observed throughout the entire clinical spectrum of the disorder but it remains an open question whether this serves as an alternative marker of reduced metabolic activity,or exists as an independent contributing process,mediated by endothelin-1 hyperexpression.Third,both metabolic and perfusion alterations may lead to repercussions at the level of network performance and structural connectivity,respectively assessable by functional and diffusion tensor imaging.Fourth and finally,elevated body fluid levels of neurofilaments are gaining interest as a biochemical mirror of axonal damage in a wide range of neurological conditions,with early rises in patients with MS appearing to be predictive of future brain atrophy.Conclusions:Recent findings from the fields of advanced neuroradiology and neurochemistry provide the promising prospect of demonstrating degenerative brain pathology in patients with MS before atrophy has installed.Although the overall level of evidence on the presented topic is still preliminary,this Review may pave the way for further longitudinal and multimodal studies exploring the relationships between the above

关键词： Brain atrophy magnetic resonance imaging multiple sclerosis neurodegeneration neurofilaments

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Are neurofilaments,Neuron-Specific Enolase and S100B Biomarkers of Chronic Insomnia Disorder?

Are Neurofilaments,Neuron-Specific Enolase and S100B Biomark...

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华东六省一市第二十三次神经病学学术会议暨2016年浙江...

作者： Ping Zhang Gui-Hai Chen Lan Xia Fang Wang Qi-Guo Wei Department of Neurology the Affiliated Chaohu Hospital of Anhui Medical Universityand the Center in Psychologic Medicine of Anhui Province Department of Neurology the First Affiliated Hospital of Anhui Medical University Department of Neurology the Second Affiliated Hospital of Anhui Medical University

Objectives:The aim of this study was to investigate whether serum neurofilaments(Nfs),neuron-specific enolase(NSE) and S100 calcium binding protein B(S100 B) in patients with chronic insomnia disorder(CID) were:(1) higher than those in healthy individuals;(2) lower in post-therapy CID patients than free-therapy patients;(3)associated with their impaired functions,including poor sleep quality,and reduced cognitive function(comprehensive cognition and memory performance in a specific task).Methods:Forty insomniac outpatients were categorized into free-therapy CID group(ft-CID,n = 40) and among forty insomniac outpatients,twenty-four patients were selected after six months treatment as re-visiting CID group(rv-CID,n = 24).Twenty demographically similar healthy subjects who accompanied the patients or had a medical examination were selected as negative controls.These subjects were assessed with the polysomnography(PSG) for 2 consecutive nights,On the morning following the second night,they completed a series of questionnaires assessing and neuropsychological tests,Pittsburgh Sleep Quality Index(PSQI),the 17-item Hamilton Depression Rating Scale(HAMD-17),the 14-item Hamilton Anxiety Scale(HAMA-14),and the Chinese-Beijing Version of Montreal Cognitive Assessment(MoCA-C).The special memory was evaluated with the Nine Box Maze Test.Serum Nfs,NSE and S100 B levels were quantified with a quantitative sandwich enzyme-linked immunosorbent assay(ELISA).Results:① Compared to the controls,the PSQI,HAMD-17,HAMD-S,HAMA-S,HAMA-17 and MoCA-C scores were significantly higher in the ft-CID and rv-CID group(Ps 0.05) was insignificant.② The ft-CID group and the rv-CID group had higher serum NfH,NfL and S100 B than the HC group(Ps < 0.05).Furthermore,the rv-CID patients had lower serum NfL,NfH,NSE than the ft-CID patients(Ps <

关键词： Chronic insomnia disorder neurofilaments Neuron-specific enolase S100 calcium binding protein B Serum

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CSF biomarkers in multiple sclerosis:beyond neuroinflammation

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Neuroimmunology and Neuroinflammation 2021年第1期8卷 14-41页

作者： Simona Toscano Francesco Patti Department"GF Ingrassia" Section of NeurosciencesMultiple Sclerosis CenterUniversity of CataniaCatania 95123Italy

For many years,quantifiable biomarkers in neurological diseases have represented a hot topic.In multiple sclerosis(MS),cerebrospinal fluid biomarkers have played a diagnostic role since the introduction of Poser's criteria in 1983,with IgG oligoclonal bands playing a supporting role in an epoch prior to magnetic resonance imaging and a complementary one after the introduction of McDonald criteria in 2001.Nowadays,that supporting role has turned into a main one in substituting for dissemination in time and defining the diagnosis of MS in patients with a first clinical event,according to the 2017 revised McDonald criteria.Possibly kappa free light chains,N-CAM,chitinase 3-like protein 1 and IgM oligoclonal bands,not yet implemented in clinical practice,could similarly gain importance in the near future.Furthermore,the increasing knowledge of molecular mechanisms leading to chronic inflammation has enhanced interest in looking for biomarkers of disease activity,better defining the MS phenotype and patients with highly active disease.Accordingly,myelin proteins,intermediate filaments,metalloproteinases and other molecules involved in the inflammatory cascade,are currently under investigation.Finally,it has long been known that axonal loss occurs from the early phases,leading to a progressive neurological deterioration.Since established criteria to assess treatment failure and transition to progressive forms are still lacking,both treatment response and prognostic biomarkers would be useful to predict MS course,and neurofilaments seem to have this potential.The purpose of this review article was to illustrate biomarkers that have been already validated or require further validation after proving to be useful in exploratory studies and potentially could prove useful in clinical practice in the coming years.

关键词： Multiple sclerosis biomarkers cerebrospinal fluid neurofilaments oligoclonal bands disease activity

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