Dendritic and synaptic pathology in experimental autoimmune encephalomyelitis.
Evidence has shown that excitotoxicity may contribute to the loss of central nervous system axons and oligodendrocytes in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Because dendrites and synapses are vulnerable to excitotoxicity, we examined these structures in acute and chronic models of EAE. Immunostaining for microtubule-associated protein-2 showed that extensive dendritic beading occurred in the white matter of the lumbosacral spinal cord (LSSC) during acute EAE episodes and EAE relapses. Retrograde labeling confirmed that most motoneuron dendrites were beaded in the white matter of the LSSC in acute EAE. In contrast, only mild swelling was observed in the gray matter of the LSSC. Dendritic beading showed marked recovery during EAE remission and after EAE recovery. In addition, synaptophysin, synapsin I, and PSD-95 immunoreactivities were significantly reduced in both the gray and white matter of the LSSC during acute EAE episodes and EAE relapses, but showed partial recovery during EAE remission and after EAE recovery. Pathologically, both dendritic beading and the reduction in synaptic protein immunoreactivity were well correlated with inflammatory cell infiltration in the LSSC at different EAE stages. We propose that dendritic and synaptic damage in the spinal cord may contribute to the neurological deficits in EAE.
Zhu
Bing
B
Brain Research Center, Vancouver Hospitals and Health Sciences Center, The University of British Columbia, Vancouver, Canada. bzhu@rics.bwh.harvard.edu
Luo
Liqing
L
Moore
G R Wayne
GR
Paty
Donald W
DW
Cynader
Max S
MS
D000208:Acute Disease; D000818:Animals; D001370:Axonal Transport; D002908:Chronic Disease; D003712:Dendrites / Q000473:pathology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009046:Motor Neurons / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000473:pathology*; D013569:Synapses / Q000473:pathology*