INIMEC - CONICET   05467
INSTITUTO DE INVESTIGACION MEDICA MERCEDES Y MARTIN FERREYRA
Unidad Ejecutora - UE
artículos
Título:
Myelin-associated glycoprotein protects neurons from excitotoxicity
Autor/es:
PABLO HECTOR HORACIO LOPEZ; ABDULAH S. AHMAD; NIRAJ R. MEHTA; MAYU TONER; ELIZABETH A. ROWLAND; JIANSANG ZHANG; SYLVAIN DORE; RONALD L. SCHNAAR
Revista:
JOURNAL OF NEUROCHEMISTRY
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Año: 2011 vol. 116 p. 900 - 908
ISSN:
0022-3042
Resumen:
In addition to supporting rapid nerve conduction, myelination nurtures
and stabilizes axons and protects them from acute toxic insults. One
myelin molecule that protects and sustains axons is myelin-associated
glycoprotein (MAG). MAG is expressed on the innermost wrap of myelin,
apposed to the axon surface, where it interacts with axonal receptors
that reside in lateral membrane domains including gangliosides, the
glycosylphosphatidylinositol-anchored Nogo receptors, and β1-integrin.
We report here that MAG protection extends beyond the axon to the
neurons from which those axons emanate, protecting them from
excitotoxicity. Compared to wild type mice, Mag-null mice displayed
markedly increased seizure activity in response to intraperitoneal
injection of kainic acid, an excitotoxic glutamate receptor agonist.
Mag-null mice also had larger lesion volumes in response to
intrastriatal injection of the excitotoxin NMDA. Prior injection of a
soluble form of MAG partially protected Mag-null mice from NMDA-induced
lesions. Hippocampal neurons plated on proteins extracted from wild-type
rat or mouse myelin were resistant to kainic acid-induced
excitotoxicity, whereas neurons plated on proteins from Mag-null myelin
were not. Protection was reversed by anti-MAG antibody and replicated by
addition of soluble MAG. MAG-mediated protection from excitotoxicity
was dependent on Nogo receptors and β1-integrin. We conclude that MAG
engages membrane-domain resident neuronal receptors to protect neurons
from excitotoxicity, and that soluble MAG mitigates excitotoxic damage
in vivo.