PMID- 14662515
OWN - NLM
STAT- MEDLINE
DCOM- 20040224
LR  - 20191122
IS  - 0006-8950 (Print)
IS  - 0006-8950 (Linking)
VI  - 127
IP  - Pt 2
DP  - 2004 Feb
TI  - Co-localization of sodium channel Nav1.6 and the sodium-calcium exchanger at 
      sites of axonal injury in the spinal cord in EAE.
PG  - 294-303
AB  - Axonal degeneration contributes to the development of non-remitting neurological 
      deficits and disability in multiple sclerosis, but the molecular mechanisms that 
      underlie axonal loss in multiple sclerosis are not clearly understood. Studies of 
      white matter axonal injury have demonstrated that voltage-gated sodium channels 
      can provide a route for sodium influx into axons that triggers reverse operation 
      of the Na(+)/Ca(2+) exchanger (NCX) and subsequent influx of damaging levels of 
      intra-axonal calcium. The molecular identities of the involved sodium channels 
      have, however, not been determined. We have previously demonstrated extensive 
      regions of diffuse expression of Na(v)1.6 and Na(v)1.2 sodium channels along 
      demyelinated axons in experimental allergic encephalomyelitis (EAE). Based on the 
      hypothesis that the co-localization of Na(v)1.6 and NCX along extensive regions 
      of demyelinated axons may predispose these axons to injury, we examined the 
      expression of myelin basic protein, Na(v)1.2, Na(v)1.6, NCX and beta-amyloid 
      precursor protein (beta-APP), a marker of axonal injury, in the spinal cord 
      dorsal columns of mice with EAE. We demonstrate a significant increase in the 
      number of demyelinated axons demonstrating diffuse Na(v)1.6 and Na(v)1.2 sodium 
      channel immunoreactivity in EAE (92.2 +/- 2.1% of beta-APP positive axons were 
      Na(v)1.6-positive). Only 38.0 +/- 2.9% of beta-APP positive axons were Na(v)1.2 
      positive, and 95% of these co-expressed Na(v)1.6 together with Na(v)1.2. Using 
      triple-labelled fluorescent immunohistochemistry, we demonstrate that 73.5 +/- 
      4.3% of beta-APP positive axons co-express Na(v)1.6 and NCX, compared with 4.4 
      +/- 1.0% in beta-APP negative axons. Our results indicate that co-expression of 
      Na(v)1.6 and NCX is associated with axonal injury in the spinal cord in EAE.
FAU - Craner, Matthew J
AU  - Craner MJ
AD  - Department of Neurology, PVA/EPVA Center for Neuroscience Research, Yale School 
      of Medicine, New Haven, CT 06510, USA.
FAU - Hains, Bryan C
AU  - Hains BC
FAU - Lo, Albert C
AU  - Lo AC
FAU - Black, Joel A
AU  - Black JA
FAU - Waxman, Stephen G
AU  - Waxman SG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20031208
PL  - England
TA  - Brain
JT  - Brain : a journal of neurology
JID - 0372537
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (NAV1.2 Voltage-Gated Sodium Channel)
RN  - 0 (NAV1.6 Voltage-Gated Sodium Channel)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Scn2a protein, mouse)
RN  - 0 (Scn8a protein, mouse)
RN  - 0 (Sodium Channels)
RN  - 0 (Sodium-Calcium Exchanger)
SB  - IM
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Axons/*metabolism/pathology
MH  - Encephalomyelitis, Autoimmune, Experimental/*metabolism/pathology
MH  - Female
MH  - Male
MH  - Mice
MH  - Myelin Sheath/pathology
MH  - NAV1.2 Voltage-Gated Sodium Channel
MH  - NAV1.6 Voltage-Gated Sodium Channel
MH  - Nerve Degeneration/*metabolism/pathology
MH  - Nerve Tissue Proteins/*metabolism
MH  - Sodium Channels/*metabolism
MH  - Sodium-Calcium Exchanger/*metabolism
MH  - Spinal Cord/metabolism/pathology
EDAT- 2003/12/10 05:00
MHDA- 2004/02/26 05:00
CRDT- 2003/12/10 05:00
PHST- 2003/12/10 05:00 [pubmed]
PHST- 2004/02/26 05:00 [medline]
PHST- 2003/12/10 05:00 [entrez]
AID - awh032 [pii]
AID - 10.1093/brain/awh032 [doi]
PST - ppublish
SO  - Brain. 2004 Feb;127(Pt 2):294-303. doi: 10.1093/brain/awh032. Epub 2003 Dec 8.