Quantitative evidence for neurofilament heavy subunit aggregation in motor neurons of spinal cords of patients with amyotrophic lateral sclerosis

Mendonça, Deise M. F.; Chimelli, Leila; Martínez, Ana Maria Blanco

doi:10.1590/s0100-879x2005000600015

Cited by 37 publications

(18 citation statements)

References 36 publications

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“…Similar changes have been reported previously in spinal motor neuron perikarya in amyotrophic lateral sclerosis (ALS), where damage to lower motor neurons is a characteristic feature [22]. In our study, we also examined a case of ALS as a positive control, which indeed showed phosphorylated NF-H immunoreactivity in perikarya (not shown).…”

Section: Discussionsupporting

confidence: 85%

Multiple Sclerosis: Neurofilament Pathology in Spinal Motor Neurons

Müller-Wielsch¹,

Cannella²,

Raine³

2017

J Mult Scler

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Objective: While traditionally a disorder of myelin, in multiple sclerosis (MS) neuronal and axonal damage has in recent years become an important topic of clinical relevance. To address this, alterations in neurofilament phosphorylation, known markers of neuronal health, were investigated in anterior horn cells in MS spinal cord tissue for signs of motor neuron damage. Methods:Spinal cord tissue was examined from 13 MS and 6 control patients. Fresh frozen sections were labelled with antibodies against phosphorylated and non-phosphorylated epitopes of neurofilament H (NF-H) and analyzed by light microscopy. Results:In MS, increased expression of phosphorylated NF-H in spinal motor neuron perikarya (abnormal for neurons) occurred in 61.5% of cases, mostly in chronic active lesions, with the strongest immunoreactivity at the lumbar level. Inflammatory activity was common in chronic active but rare in chronic silent lesions. In one case with an acute lesion, we saw swollen axons positive for non-phosphorylated NF-H, a pathologic marker in axons, but no signs of perikaryal damage. Expression of non-phosphorylated NF-H in spinal motor neuron perikarya was similar in both MS and controls. Conclusion:In line with previous studies, our findings implicate anterior horn cell damage as a common feature in MS. We propose that underlying mechanisms may involve reduced synaptic input and/or retrograde degeneration, subjects which remain to be investigated. For the neuron count of a subgroup of MS cases, 5 serial sections of each patient stained with Nissl stain (0.075 % cresyl violet) were examined with stereological methods using StereoInvestigator software (MicroBrightField Inc., Williston, VT, USA). In the anterior horn as the region of interest, all neuronal perikarya were counted, measured and grouped according to their size into motor neurons (diameter ≥ 24 μm) and interneurons (diameter (≥ 10-24 μm) [21]. For evaluation, total numbers of motor neurons per patient were compared. Further details of the procedure can be found in an earlier publication [11].Images were captured with a digital camera (Axiocam and software by Carl Zeiss); GraphPadPrism software was used for graph production. ResultsEstablished, gliotic lesions devoid of myelin and displaying variable degrees of axonal degeneration were common in all cases with chronic lesions but inflammatory changes (reflecting ongoing demyelination), were only seen in chronic active lesions. Such changes comprised perivascular cuffs and scattered lipid-laden macrophages in the white matter (mainly anterior or lateral columns) and occasional collections of small lymphocytes within the meninges.By immunocytochemistry, clear differences were seen between MS and control cases in the expression of phosphorylated NF-H in anterior horn cell perikarya. Specifically, eight of thirteen MS patients showed widespread phosphorylated (abnormal) NF-H positivity compared to none of the controls (3 healthy, 2 OND: olivopontocerebellar degeneration and polyglucosan inclusion disease...

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Section: Discussionsupporting

confidence: 85%

Multiple Sclerosis: Neurofilament Pathology in Spinal Motor Neurons

Müller-Wielsch¹,

Cannella²,

Raine³

2017

J Mult Scler

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“…Neu- rofilaments are composed of three different subunits: NF-L, NF-M, and NF-H. Studies have shown that defects in NF-H might be a possible cause of amyotrophic lateral sclerosis, a degenerative disorder of motor neurons in the cortex, brainstem, and spinal cord characterized by abnormal accumulation of NFs in perikarya and proximal axons (27,28). Two peptides were identified for this protein, one covers coil 1B (peptide 205-213), and the other covers coil 2B (peptide 353-372).…”

Section: Discussionmentioning

confidence: 99%

Proteomics Identification of Proteins in Human Cortex Using Multidimensional Separations and MALDI Tandem Mass Spectrometer

Pan

Shi

Jin

et al. 2007

Molecular & Cellular Proteomics

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It is essential to characterize the proteome of various regions of human brain because most, if not all, neurodegenerative diseases are region-specific. Here we report an in-depth proteomics identification of proteins extracted from the frontal cortex, a region playing a critical role in cognitive function. The integrated proteomics analytical flow consisted of biochemical fractionation, strong cation exchange chromatography, reverse phase liquid chromatography, and MALDI-TOF/TOF mass spectrometric analysis. In total, 812 proteins were confidently identified with two or more peptides. These proteins demonstrated diverse isoelectric points and molecular weights and are involved in several molecular functions, including protein binding, catalytic activity, transport, structure, and signal transduction. A number of proteins known to be associated with neurodegenerative diseases were also identified. Detailed characterization of these proteins will supply the necessary information to appropriately interpret proteins associated with aging and/or age-related neurodegenerative diseases. Finally 140 proteins found in the cortical proteome were present in the proteome of cerebrospinal fluid, providing tissue-specific candidates for biomarker discovery in body fluid.

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“…Each analyzed area was approximately the same in size. In the given region, we evaluated the sum of all the pixel intensity or optical density values (Mendonça et al, 2005). We obtained the numerical values from twenty different regions in each tissue, and then calculated the average, which represented the specified marker in the given tissue.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Effects of sodium ferulate on preventing steroid-induced femoral head osteonecrosis in rabbits

Tian

Dang

Wang

et al. 2013

J. Zhejiang Univ. Sci. B

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Abstract:The aim of this study is to investigate the effects and possible mechanisms of sodium ferulate (SF) on anti-apoptosis in steroid-induced femoral head osteonecrosis in rabbits. Japanese white rabbits were randomly divided into three groups (control group, treatment group, and model group), each with 24 rabbits. The model and treatment groups were first injected with an intravenous dose of horse serum, 10 ml/kg, three weeks later with an intravenous dose of 7.5 ml/kg, and two weeks later with an intramuscular dose of methylprednisolone, 45 mg/kg, three times in order to establish rabbit models of osteonecrosis. Concurrently, the treatment group was injected with intravenous doses of SF 20 mg/kg for two weeks, once per day. Three time points, Weeks 2, 4, and 8, were selected after modeling was completed. Osteonecrosis was verified by histopathology with haematoxylin-eosin (HE) staining. The apoptosis rate of osteonecrosis was observed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The apoptosis expressions of caspase-3 and Bcl-2 were analyzed by immunohistochemistry and Western blot. The rabbit models of osteonecrosis were successfully established and observed by HE staining. SF was effective in intervening in apoptosis and decreasing the apoptosis rate in femoral head necrosis by the immunohistochemistry and TUNEL assay (P<0.01). Western blot analysis indicated that there were statistical significances in the protein levels of caspase-3 and Bcl-2 (P<0.01). SF has a protective effect by reducing the incidence of early steroid-induced femoral head necrosis in rabbits, effectively intervening in apoptosis through decreasing caspase-3 expression and up-regulating Bcl-2 expression.

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Quantitative evidence for neurofilament heavy subunit aggregation in motor neurons of spinal cords of patients with amyotrophic lateral sclerosis

Cited by 37 publications

References 36 publications

Multiple Sclerosis: Neurofilament Pathology in Spinal Motor Neurons

Multiple Sclerosis: Neurofilament Pathology in Spinal Motor Neurons

Proteomics Identification of Proteins in Human Cortex Using Multidimensional Separations and MALDI Tandem Mass Spectrometer

Effects of sodium ferulate on preventing steroid-induced femoral head osteonecrosis in rabbits

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