KAINATE-EVOKED CHANGES IN DYSTROPHIN MESSENGER-RNA LEVELS IN THE RAT HIPPOCAMPUS

Dystrophin and dystroglycan messenger RNAs are expressed in specific b rain areas, including regions of the cortex and the hippocampus, and i n such neurons dystrophin has been localized to postsynaptic densities . In the present study we examined by in situ hybridization the effect of neuronal activation and neurotoxicity induced by kainate and penty lenetetrazole administered in vivo on dystrophin and dystroglycan expr ession in the rat brain. Kainate injection resulted in a transient but dramatic decrease in dystrophin transcript levels in the dentate gyru s granule cells, neurons nor affected by kainate neurotoxicity, 6 h af ter injection. There was also a strong, concomitant increase in dystro phin messenger RNA levels in the CA3 subfield. At 24-72 h after kainat e injection, the dystrophin transcript in the dentate granule cells re turned to control levels, while it decreased gradually in the CA subfi elds, coinciding with the neurodegeneration observed in these areas. C omparable results were obtained with pan-dystrophin probes and probes specific to the short, G-dystrophin (Dp71) isoform that predominates i n the dentate gyrus. This indicates that any dystrophin transcript tha t might be expressed in these areas responds to kainate in the same ma nner. In contrast, kainate insult had no significant effect on the dys troglycan messenger RNA levels in these hippocampal areas at 6 h post- injection. At later times, however, there was a gradual decrease in th e dystroglycan messenger RNA in those areas which respond to the kaina te insult with extensive neuronal death. For comparison, seizures whic h are not associated with progressive neurodegeneration were induced b y pentylenetetrazole: in this situation the dystrophin and dystroglyca n messenger RNA levels remained unchanged in all areas of the hippocam pal formation. Since activation of glutamate receptors is thought to b e involved in some forms of synaptic plasticity in the adult hippocamp us, our data indicate that the dystrophin gene behaves as a candidate plasticity-related gene responding to glutamate. (C) 1998 IBRO. Publis hed by Elsevier Science Ltd.