Journal of Neuroscience, Vol 7, 753-759, Copyright © 1987 by Society for Neuroscience
Enkephalin biosynthesis and enkephalin gene expression are increased in hippocampal mossy fibers following a unilateral lesion of the hilus
JD White, CM Gall and JF McKelvy
The biosynthesis and posttranslational processing of proenkephalin and the
level of preproenkephalin mRNA were investigated in the mossy fiber system
of the granule cells of the hippocampus in the presence or absence of a
unilateral lesion of the hilus, a procedure that produces an episode of
recurrent bilateral hippocampal seizures lasting several hours. Both
immunocytochemistry and radioimmunoassay (RIA) have demonstrated that the
hilus lesion leads to large bilateral increases in enkephalin
immunoreactivity in the mossy fiber system. In the present study, RIA data
indicate that following an initial decline in immunoreactivity, enkephalin
content within the mossy fibers first begins to increase between 18 and 24
hr after lesioning. Using the technique of in vivo radiolabeling and
high-performance liquid chromatographic purification of identified
radiolabeled peptides, we observed a 14-fold increase in incorporation of
radiolabeled methionine into Met5-enkephalin at 24-30 hr postlesion, as
compared with control animals, when Met5-enkephalin was purified from the
mossy fiber terminal fields. To examine the posttranslational proteolytic
processing of proenkephalin, the biosynthesis of 5 additional Met5-
enkephalin-containing peptides was also examined. We determined that the
posttranslational processing of proenkephalin did not yield exclusively
penta-, hepta-, and octapeptides but larger opioid peptides as well in both
control and lesioned animals, and that the ratio of the enkephalin peptides
was not altered following the lesion. Measurement of preproenkephalin
messenger RNA levels in the granule cells by Northern analysis revealed a
marked increase following the lesion. Compared with the control animals,
preproenkephalin mRNA was 8.5-fold higher in the contralateral dentate
gyrus at 12 hr postlesion and 14- to 15-fold higher by 24 hr.(ABSTRACT
TRUNCATED AT 250 WORDS)