Both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis 
(EAE), its animal model, involve inflammatory attack on central nervous system 
(CNS) white matter, leading to demyelination and axonal damage. Changes in 
astrocytic morphology and function are also prominent features of MS and EAE. 
Resting astrocytes form a network that is interconnected through gap junctions, 
composed mainly of connexin43 (Cx43) protein. Although astrocytic gap junctional 
connectivity is known to be altered in many CNS pathologies, little is known 
about Cx43 expression in inflammatory demyelinating disease. Therefore, we 
evaluated the expression of Cx43 in spinal cords of EAE mice compared with 
healthy controls. Lumbar ventral white matter areas were heavily infiltrated 
with CD11beta-immunoreactive monocytes, and within these infiltrated regions 
loss of Cx43 immunoreactivity was evident. These regions also showed axonal 
dystrophy, demonstrated by the abnormally dephosphorylated heavy-chain 
neurofilament proteins. Astrocytes in these Cx43-depleted lesions were strongly 
glial fibrillary acidic protein reactive. Significant loss (38%) of Cx43 protein 
in EAE mouse at the lumbar portion of spinal cords was confirmed by Western blot 
analysis. Decreased Cx43 transcript level was also observed on cDNA microarray 
analysis. In addition to changes in Cx43 expression, numerous other genes were 
altered, including those encoding adhesion and extracellular matrix proteins. 
Our data support the notion that, in addition to damage of myelinating glia, 
altered astrocyte connectivity is a prominent feature of inflammatory 
demyelination.