Connexin 43 gap junction proteins are up-regulated in remyelinating spinal cord.
Alterations in the expression of gap junction proteins have previously been observed in several diseases affecting the central nervous system; however, the status of connexin 43 (Cx43) has not yet been reported in spinal cord remyelination. We studied Cx43 expression in demyelination and remyelination by using a chronic guinea pig model of experimental allergic encephalomyelitis (EAE). Hartley guinea pigs were immunized with homogenized whole CNS and complete Freund's adjuvant. Animals became chronically ill by day 40 postimmunization, and animals with paralysis were entered into the study. Animals were treated on days 40-60 postimmunization with either saline or drugs that promote remyelination: an adenosine amine congener (100 mug/kg), an anti-alpha4-integrin blocker (CT301; ELN 69299; 30 mg/kg), or a combination of both drugs. Remyelination was induced in all drug-treated groups. Cx43 expression was virtually absent in demyelinated lesions of saline-treated controls compared with healthy tissue and normal appearing white matter (P < 0.001), whereas Cx43 was considerably increased (300-500%) in remyelinating lesions of all treatment groups (P < 0.001), most notably in CT301-treated animals. These changes in Cx43 expression indicate that Cx43 may beimportant for recovery from neuroinflammation.
Roscoe
W A
WA
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
Messersmith
E
E
Meyer-Franke
A
A
Wipke
B
B
Karlik
S J
SJ
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006168:Guinea Pigs; D039441:Integrin alpha4 / Q000187:drug effects / Q000276:immunology; D009186:Myelin Sheath / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology
D000906:Antibodies; D018031:Connexin 43; D017630:Connexins; D039441:Integrin alpha4; C106045:adenosine amine congener; D000241:Adenosine