Diffuse Traumatic Injury in the Mouse Disrupts Axon-Myelin Integrity in the Cerebellum
Özen, Ilknur LU ; Arkan, Sertan LU ; Clausen, Fredrik LU ; Ruscher, Karsten LU and Marklund, Niklas LU
(2022)
In Journal of Neurotrauma
39(5-6).
p.411-422
- Abstract
Cerebellar dysfunction after traumatic brain injury (TBI) is commonly suspected based on clinical symptoms, although cerebellar pathology has rarely been investigated. To address the hypothesis that the cerebellar axon-myelin unit is altered by diffuse TBI, we used the central fluid percussion injury (cFPI) model in adult mice to create widespread axonal injury by delivering the impact to the forebrain. We specifically focused on changes in myelin components (myelin basic protein [MBP], 2′,3′-cyclic nucleotide 3′-phosphodiesterase [CNPase], nodal/paranodal domains [neurofascin (Nfasc), ankyrin-G], and phosphorylated neurofilaments [SMI-31, SMI-312]) in the cerebellum, remote from the impact, at two, seven, and 30 days post-injury (dpi).... (More)
Cerebellar dysfunction after traumatic brain injury (TBI) is commonly suspected based on clinical symptoms, although cerebellar pathology has rarely been investigated. To address the hypothesis that the cerebellar axon-myelin unit is altered by diffuse TBI, we used the central fluid percussion injury (cFPI) model in adult mice to create widespread axonal injury by delivering the impact to the forebrain. We specifically focused on changes in myelin components (myelin basic protein [MBP], 2′,3′-cyclic nucleotide 3′-phosphodiesterase [CNPase], nodal/paranodal domains [neurofascin (Nfasc), ankyrin-G], and phosphorylated neurofilaments [SMI-31, SMI-312]) in the cerebellum, remote from the impact, at two, seven, and 30 days post-injury (dpi). When compared with sham-injured controls, cerebellar MBP and CNPase protein levels were decreased at 2 dpi that remained reduced up to 30 dpi. Diffuse TBI induced different effects on neuronal (Nfasc 186, Nfasc 140) and glial (Nfasc 155) neurofascin isoforms that play a key role in the assembly of the nodes of Ranvier. Expression of Nfasc 140 in the cerebellum increased at 7 dpi, in contrast to Nfasc 155 levels, which were decreased. Although neurofascin binding partner ankyrin-G protein levels decreased acutely after cFPI, its expression levels increased at 7 dpi and remained unchanged up to 30 dpi. The TBI-induced reduction in neurofilament phosphorylation (SMI-31) observed in the cerebellum was closely associated with decreased levels of the myelin proteins MBP and CNPase. This is the first evidence of temporal and spatial structural changes in the axon-myelin unit in the cerebellum, remote from the location of the impact site, in a diffuse TBI model in mice.
(Less)
- author
- Özen, Ilknur
LU
; Arkan, Sertan
LU
; Clausen, Fredrik
LU
; Ruscher, Karsten
LU
and Marklund, Niklas
LU
- organization
- publishing date
- 2022-03
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cerebellum, CNPase, fluid percussion, myelin, myelin basic protein (MBP), neurofilament, traumatic brain injury
- in
- Journal of Neurotrauma
- volume
- 39
- issue
- 5-6
- pages
- 12 pages
- publisher
- Mary Ann Liebert, Inc.
- external identifiers
-
- pmid:35018831
- scopus:85125554080
- ISSN
- 0897-7151
- DOI
- 10.1089/neu.2021.0321
- language
- English
- LU publication?
- yes
- id
- 32d85e4d-dcf8-46bd-a0ee-13d72f11b874
- date added to LUP
- 2022-05-12 16:24:15
- date last changed
- 2024-09-19 21:37:49
@article{32d85e4d-dcf8-46bd-a0ee-13d72f11b874,
abstract = {{<p>Cerebellar dysfunction after traumatic brain injury (TBI) is commonly suspected based on clinical symptoms, although cerebellar pathology has rarely been investigated. To address the hypothesis that the cerebellar axon-myelin unit is altered by diffuse TBI, we used the central fluid percussion injury (cFPI) model in adult mice to create widespread axonal injury by delivering the impact to the forebrain. We specifically focused on changes in myelin components (myelin basic protein [MBP], 2′,3′-cyclic nucleotide 3′-phosphodiesterase [CNPase], nodal/paranodal domains [neurofascin (Nfasc), ankyrin-G], and phosphorylated neurofilaments [SMI-31, SMI-312]) in the cerebellum, remote from the impact, at two, seven, and 30 days post-injury (dpi). When compared with sham-injured controls, cerebellar MBP and CNPase protein levels were decreased at 2 dpi that remained reduced up to 30 dpi. Diffuse TBI induced different effects on neuronal (Nfasc 186, Nfasc 140) and glial (Nfasc 155) neurofascin isoforms that play a key role in the assembly of the nodes of Ranvier. Expression of Nfasc 140 in the cerebellum increased at 7 dpi, in contrast to Nfasc 155 levels, which were decreased. Although neurofascin binding partner ankyrin-G protein levels decreased acutely after cFPI, its expression levels increased at 7 dpi and remained unchanged up to 30 dpi. The TBI-induced reduction in neurofilament phosphorylation (SMI-31) observed in the cerebellum was closely associated with decreased levels of the myelin proteins MBP and CNPase. This is the first evidence of temporal and spatial structural changes in the axon-myelin unit in the cerebellum, remote from the location of the impact site, in a diffuse TBI model in mice. </p>}},
author = {{Özen, Ilknur and Arkan, Sertan and Clausen, Fredrik and Ruscher, Karsten and Marklund, Niklas}},
issn = {{0897-7151}},
keywords = {{cerebellum; CNPase; fluid percussion; myelin; myelin basic protein (MBP); neurofilament; traumatic brain injury}},
language = {{eng}},
number = {{5-6}},
pages = {{411--422}},
publisher = {{Mary Ann Liebert, Inc.}},
series = {{Journal of Neurotrauma}},
title = {{Diffuse Traumatic Injury in the Mouse Disrupts Axon-Myelin Integrity in the Cerebellum}},
url = {{http://dx.doi.org/10.1089/neu.2021.0321}},
doi = {{10.1089/neu.2021.0321}},
volume = {{39}},
year = {{2022}},
}