NEUROTENSIN AND NEUROMEDIN-N BRAIN LEVELS AFTER FORNIX TRANSECTION - EVIDENCE FOR AN EFFICIENT NEUROTENSIN PRECURSOR PROCESSING IN SUBICULAR NEURONS

High levels of neurotensin/neuromedin N precursor mRNA, but few if any NT-positive perikarya have been detected in the dorsal subiculum of t he adult rat or human hippocampus. This apparent discrepancy was tenta tively ascribed to a lack of precursor mRNA translation or to a poor p recursor posttranslational processing in neurons of the hippocampus. A nother hypothesis is that in long neuronal pathways, maturation of neu ropeptide precursors and derived peptides occurs during axonal transpo rt to terminals, a process which accounts for the lack of peptide dete ction in cell bodies, In order to test this hypothesis, we performed s urgical transection of the fornix to interrupt axonal transport of put ative NT/NN products arising from the dorsal hippocampus and measured NT and NN levels in different brain regions. In the mamillary bodies, the main projection area of the dorsal subiculum, NN and NT levels wer e highly reduced 4 or 14 days after the septo-hippocampal transection which was correlated with a slight increase in NN and NT levels in the dorsal hippocampus and the retrosplenial cortex of 4 days lesioned an imals. An increase in hypothalamic NN levels was also detected 14 days after the lesion. These data suggest that the peptide precursor proce ssing can take place during the axonal transport, as shown here for ne urotensin and neuromedin N from subicular neurons to their efferent br ain areas such as the mamillary bodies.