Demyelination and axonal damage in a non-human primate model of multiple sclerosis.
The demyelinating plaque is the paradigmatic lesion of multiple sclerosis (MS), but only recently attention has been given to axonal damage and to its role in the pathophysiology of disease. Albeit the possible relevance of axonal loss in MS and its experimental models, the amount and timing of axonal sufferance has been addressed only in experimental autoimmune encephalomyelitis (EAE) of rodents. In this report we observed that, in the marmoset model of EAE, axonal damage occurs early during the demyelinating process as assessed by immunoreactivity for amyloid precursor protein (APP) and non-phosphorylated neurofilaments (SMI-32 positive) detected mostly in early active lesions compared to late active and normal appearing white matter. The rare occurrence of morphological features of axonal transection, such as APP or SMI-32 positive spheroids and swellings, as well as an increase of neurofilament density in the demyelinated axons without accumulation of electron dense organelles or osmiophilic bodies, at electron microscopy, suggests that early axonal damage may be, at least in part, a reversible process. These findings are of relevance for the development of therapies, which can protect axons and enhance their function and survival.
Department of Neurological Sciences and Vision, University of Genoa, Via De Toni 5, 16132 Genoa, Italy. neurolab@cisi.unige.it
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G
Mancardi
B
B
Hart
L
L
Roccatagliata
H
H
Brok
D
D
Giunti
R
R
Bontrop
L
L
Massacesi
E
E
Capello
A
A
Uccelli
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000473:pathology; D002144:Callithrix; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology*
D016564:Amyloid beta-Protein Precursor