eprintid: 177309 rev_number: 193 eprint_status: archive userid: 608 dir: disk0/00/17/73/09 datestamp: 2010-11-04 21:42:56 lastmod: 2021-09-19 23:03:06 status_changed: 2012-03-20 10:06:46 type: article metadata_visibility: show item_issues_count: 0 creators_name: Petzold, A creators_name: Gveric, D creators_name: Groves, M creators_name: Schmierer, K creators_name: Grant, D creators_name: Chapman, M creators_name: Keir, G creators_name: Cuzner, L creators_name: Thompson, EJ title: Phosphorylation and compactness of neurofilaments in multiple sclerosis: Indicators of axonal pathology ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 keywords: neurofilament phosphoforms, multiple sclerosis, axonal injury, WALLERIAN DEGENERATION, WHITE-MATTER, NOGO-A, GLUTAMATE, DAMAGE, LESIONS, PROTEINS, DISEASE, INJURY, NEURODEGENERATION abstract: Aims: Axonal pathology extends to the axonal cytoarchitecture leaving its Signature on axoskeletal proteins. This study investigated whether neurofilament (NfH) phosphorylation would relate to the dynamics of axonal pathology in multiple sclerosis (MS).Methods: NfH phosphoforms (SM132, SM134, SM135) were quantified by ELISA from microdissected samples of control and MS brain and spinal cord. Individual axons were analysed by electron microscopy, densitometrically and morphologically in adjacent tissue sections. Experiments were Carried Out pre- and post enzymatic dephosphorylation.Results: In control tissue a rostro-caudal gradient of NfH indicated an increase in axonal density from the brain gray matter towards the spinal cord. The highest levels of phosphorylated and hyperphosphorylated NfH were found in acute lesions of brain and spinal cord, in contrast to chronic lesions where levels were lower than in white matter, consistent with axonal loss. Dephosphorylated NfH was higher, but less densly packed in MS white matter axons compared to control tissue.Conclusions: The findings suggest that a less organised/compact axoskeleton or impaired axonal transport may represent an early sign of axonal pathology within the normal appearing white matter in MS. Subsequently a proportional increase of dephosphorylated NfH, aberrant phosphorylation and/or aggregation may occur whilst the protein is transported through the white matter towards the MS plaque, where hyperphosphorylated NfH dominates. (c) 2008 Elsevier Inc. All rights reserved. date: 2008-10 publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE official_url: http://dx.doi.org/10.1016/j.expneurol.2008.06.008 vfaculties: VFBRS oa_status: green pmcid: PMC2583254 language: eng primo: open primo_central: open_green article_type_text: Article verified: verified_batch elements_source: Web of Science elements_id: 96188 doi: 10.1016/j.expneurol.2008.06.008 language_elements: EN lyricists_name: Chapman, Miles lyricists_name: Cuzner, Margaret lyricists_name: Groves, Michael lyricists_name: Keir, Geoffrey lyricists_name: Petzold, Axel lyricists_name: Schmierer, Klaus lyricists_name: Thompson, Edward lyricists_id: MDCHA44 lyricists_id: MLCUZ52 lyricists_id: MJGRO65 lyricists_id: GKEIR26 lyricists_id: APETZ95 lyricists_id: KSCHM30 lyricists_id: EJTHO52 full_text_status: public publication: Experimental Neurology volume: 213 number: 2 pagerange: 326 - 335 issn: 0014-4886 citation: Petzold, A; Gveric, D; Groves, M; Schmierer, K; Grant, D; Chapman, M; Keir, G; ... Thompson, EJ; + view all <#> Petzold, A; Gveric, D; Groves, M; Schmierer, K; Grant, D; Chapman, M; Keir, G; Cuzner, L; Thompson, EJ; - view fewer <#> (2008) Phosphorylation and compactness of neurofilaments in multiple sclerosis: Indicators of axonal pathology. Experimental Neurology , 213 (2) 326 - 335. 10.1016/j.expneurol.2008.06.008 <https://doi.org/10.1016/j.expneurol.2008.06.008>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/177309/1/177309_ms6-nfh-PR-v9k.pdf