SPATIOTEMPORAL SELECTIVE EFFECTS ON BRAIN-DERIVED NEUROTROPHIC FACTORAND TRKB MESSENGER-RNA IN RAT HIPPOCAMPUS BY ELECTROCONVULSIVE SHOCK

Electroconvulsive therapy is used in the treatment of affective disord ers and schizophrenia and experimental electroconvulsive shock may ser ve as an animal model for this treatment. The aim of this study was to investigate a possible role for neurotrophins in the mechanism of act ion of experimental electroconvulsive shock and thus in clinical elect roconvulsive therapy. The effect of electroconvulsive shock on levels of messenger RNAs encoding the neurotrophin brain-derived neurotrophic factor and the receptor trkB in rat hippocampus was determined by in situ hybridization with RNA probes 1, 3, 9 and 27 h following the shoc k. Brain-derived neurotrophic factor messenger RNA levels were increas ed at 1, 3 and 9 h following the shock and normalized after 27 h. Gran ule cells of the dentate gyrus showed a more rapid response as compare d to hilar cells and pyramidal cells of CAI. Total trkB messenger RNA levels, including the transcripts for both the truncated and full leng th trkB receptor protein (gp95(trkB) and gp145(trkB), respectively), s howed a pattern of increase very similar to that of the brain-derived neurotrophic factor messenger RNA. However, using a probe selective fo r the full length (gp145(trkB)) trkB messenger RNA, we determined a de layed pattern of activation with significant increase only at 3 and 9 h after the shock. In hippocampus total trkB messenger RNA was found t o consist of approximately one-quarter of mRNA encoding gp145(trkB) an d three-quarters encoding gp95(trkB) as revealed by RNAase protection. While brain-derived neurotrophic factor and the truncated trkB messen ger RNAs appear to increase with a similar pattern, suggesting a simil ar mechanism of activation by electroconvulsive shock, full length rec eptor trkB messenger RNA appears to increase with a delayed pattern su ggesting a separate mechanism of activation. Electroconvulsive shock-i nduced seizures seem to include activation of a brain neurotrophin kno wn to be important for neuronal plasticity.