PMID- 17805013
OWN - NLM
STAT- MEDLINE
DCOM- 20071018
LR  - 20220331
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 66
IP  - 9
DP  - 2007 Sep
TI  - Sodium channel expression within chronic multiple sclerosis plaques.
PG  - 828-37
AB  - Multiple sclerosis (MS) is characterized by focal destruction of myelin sheaths, 
      gliotic scars, and axonal damage that contributes to the accumulation of 
      nonremitting clinical deficits. Previous studies have demonstrated coexpression 
      of sodium channel Nav1.6 and the sodium-calcium exchanger (NCX), together with 
      beta-amyloid precursor protein (beta-APP), a marker of axonal damage, in 
      degenerating axons within acute MS lesions. Axonal degeneration is less frequent 
      within chronic MS lesions than in acute plaques, although current evidence 
      suggests that axonal loss in chronic lesions ("slow burn") is a major contributor 
      to accumulating disability. It is not known, however, whether axonal 
      degenerations in chronic and acute lesions share common mechanisms, despite 
      radically differing extracellular milieus. In this study, the expression of 
      sodium channels Nav1.2 and Nav1.6 and of NCX was examined in chronic MS plaques 
      within the spinal cord. Nav1.2 immunostaining was not observed along demyelinated 
      axons in chronic lesions but was expressed by scar and reactive astrocytes within 
      the plaque. Nav1.6 immunoreactivity, which was intense at nodes of Ranvier in 
      normal appearing white matter in the same sections, was present in approximately 
      one-third of the demyelinated axons within these plaques in a patchy rather than 
      continuous distribution. NCX was not detected in demyelinated axons within 
      chronic lesions, although it was clearly present within the scar astrocytes 
      surrounding the demyelinated axons. beta-APP accumulation occurred in a small 
      percentage of axons within chronic lesions within the spinal cord, but beta-APP 
      was not preferentially present in axons that expressed Nav1.6. These observations 
      suggest that different mechanisms underlie axonal degeneration in acute and 
      chronic MS lesions, with axonal injury occurring at sites of coexpression of 
      Nav1.6 and NCX in acute lesions but independent of coexpression of these 2 
      molecules in chronic lesions.
FAU - Black, Joel A
AU  - Black JA
AD  - Department of Neurology and Paralyzed Veterans of America/United Spinal 
      Association Neuroscience Research Center, Yale University School of Medicine, New 
      Haven, CT, USA. joel.black@yale.edu
FAU - Newcombe, Jia
AU  - Newcombe J
FAU - Trapp, Bruce D
AU  - Trapp BD
FAU - Waxman, Stephen G
AU  - Waxman SG
LA  - eng
GR  - NS35058/NS/NINDS NIH HHS/United States
GR  - NS38667/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
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, human)
RN  - 0 (SCN8A protein, human)
RN  - 0 (Sodium Channels)
RN  - 0 (Sodium-Calcium Exchanger)
SB  - IM
MH  - Aged
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Cadaver
MH  - Humans
MH  - Immunohistochemistry
MH  - Middle Aged
MH  - Multiple Sclerosis, Chronic Progressive/*metabolism/*pathology
MH  - NAV1.2 Voltage-Gated Sodium Channel
MH  - NAV1.6 Voltage-Gated Sodium Channel
MH  - Nerve Tissue Proteins/*metabolism
MH  - Retrospective Studies
MH  - Sodium Channels/*metabolism
MH  - Sodium-Calcium Exchanger/metabolism
MH  - Spinal Cord/*metabolism/pathology
EDAT- 2007/09/07 09:00
MHDA- 2007/10/19 09:00
CRDT- 2007/09/07 09:00
PHST- 2007/09/07 09:00 [pubmed]
PHST- 2007/10/19 09:00 [medline]
PHST- 2007/09/07 09:00 [entrez]
AID - 00005072-200709000-00007 [pii]
AID - 10.1097/nen.0b013e3181462841 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2007 Sep;66(9):828-37. doi: 
      10.1097/nen.0b013e3181462841.