PHOSPHORYLATED NEUROFILAMENT EXPRESSION AND RESISTANCE TO KAINATE TOXICITY

Antibodies directed against phosphorylated neurofilaments, which are m ajor proteins of the neuronal cytoskeleton, usually do not label neuro nal cell bodies except in some neurological diseases. In the present s tudy, we show that in rat cortical cell cultures exposed to kainate th ere is an inverse relation between neuronal survival and the proportio n of neuronal cell bodies stained by a monoclonal antibody (clone SMI( 31)) that recognizes extensively phosphorylated neurofilament proteins (150 kDa and 200 kDa). The immunoblot analysis also revealed an incre ase in 150-kDa phosphorylated neurofilament expression in kainate-trea ted cell cultures. Furthermore, the direct quantification of viable ne urons SMI(31)-immunopositive or immunonegative in perikarya showed tha t the majority of neurons resistant to kainate toxicity expressed phos phorylated neurofilaments in their cell bodies. The percentage of viab le neurons displaying SMI(31)-immunoreactivity in their cell bodies in creased from 14.7% in control cultures to 30.0% in cultures treated wi th 10 mu M kainate. These data suggest that phosphorylated neurofilame nt expression is associated with a reduced cell vulnerability to excit otoxicity induced by kainate. Copyright (C) 1996 Elsevier Science Inc.