ALTERATIONS OF METALLOTHIONEIN-II AND APOLIPOPROTEIN-J MESSENGER-RNA LEVELS IN KAINATE-TREATED RATS

ALTHOUGH different mechanisms have been proposed, it has been suggeste d that apolipoprotein J (ApoJ) and metallothionein II (MTII), expresse d by astrocytes, are protective proteins. Alterations in their express ion may contribute to the involvement of astrocytes in epileptogenesis . We studied the expression of MTII and ApoJ es 7 days following statu s epilepticus induced in rats by intra-amygdala injection of kainate ( KA). ApoJ mRNA levels were increased in both cortex (77%, p < 0.01) an d hippocampus (64%, p < 0.02), whereas, in contrast to previous findin gs 3 days after KA injection, DNA fragmentation was not detected on ag arose gel electrophoresis, These results show that ApoJ is induced alo ng with early genes during massive apoptosis, and remains induced afte r the acute phase. MTII mRNA levels were altered only in hippocampus ( 62%, P < 0.05), whereas KA-treated rats had no seizure for 7 days. The sustained induction of MTII mRNA shows that zinc homeostasis is not r eturned to normal or alternatively that astrocytes maintain an altered phenotype in spite of normal zinc release. Polyadenylated RNA and bet a-actin mRNA levels were in contrast unaltered in cortex or hippocampu s at this time point. These specific variations in ApoJ and MTII mRNA expression during the latent period suggest that they are part of long term biochemical and/or phenotypic alterations in astrocytes, followi ng a single episode of severe seizures.