Molecular reconstruction of nodes of Ranvier after remyelination by transplanted olfactory ensheathing cells in the demyelinated spinal cord.
Myelin-forming glial cells transplanted into the demyelinated spinal cord can form compact myelin and improve conduction properties. However, little is known of the expression and organization of voltage-gated ion channels in the remyelinated central axons or whether the exogenous cells provide appropriate signaling for the maturation of nodes of Ranvier. Here, we transplanted olfactory ensheathing cells from green fluorescent protein (GFP)-expressing donor rats [GFP-olfactory ensheathing cells (OECs)] into a region of spinal cord demyelination and found extensive remyelination, which included the development of mature nodal, paranodal, and juxtaparanodal domains, as assessed by ultrastructural, immunocytochemical, and electrophysiological analyses. In remyelinated axons, Nav1.6 was clustered at nodes, whereas Kv1.2 was aggregated in juxtaparanodal regions, recapitulating the distribution of these channels within mature nodes of uninjured axons. Moreover, the recruitment of Nav and Kv channels to specific membrane domains at remyelinated nodes persisted for at least 8 weeks after GFP-OEC transplantation. In vivo electrophysiological recordings demonstrated enhanced conduction along the GFP-OEC-remyelinated axons. These findings indicate that, in addition to forming myelin, engrafted GFP-OECs provide an environment that supports the development and maturation of nodes of Ranvier and the restoration of impulse conduction in central demyelinated axons.
Department of Neurology, Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Masanori
M
Sasaki
Joel A
JA
Black
Karen L
KL
Lankford
Hajime A
HA
Tokuno
Stephen G
SG
Waxman
Jeffery D
JD
Kocsis
D000818:Animals; D001369:Axons / Q000502:physiology; D003711:Demyelinating Diseases / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D009186:Myelin Sheath / Q000473:pathology / Q000502:physiology*; D009830:Olfactory Bulb / Q000502:physiology / Q000503:physiopathology; D011901:Ranvier's Nodes / Q000502:physiology* / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012903:Smell / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology* / Q000503:physiopathology