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Journal of Neuroscience, Vol 8, 1852-1862, Copyright © 1988 by Society for Neuroscience
Seizures induce dramatic and distinctly different changes in enkephalin, dynorphin, and CCK immunoreactivities in mouse hippocampal mossy fibers
C Gall
Department of Anatomy and Neurobiology, University of California, Irvine 92717.
Light microscopic immunocytochemical techniques were used to evaluate the
influence of recurrent limbic seizure activity on the immunoreactivity for
3 neuropeptides--enkephalin, dynorphin, and cholecystokinin
(CCK)--contained within the mouse hippocampal mossy fiber axonal system.
Seizures were induced either by the placement of a small unilateral
electrolytic lesion in the dentate gyrus hilus or by intraventricular
injection of kainic acid. Both treatments induce epileptiform activity in
hippocampus lasting several hours. Four days after either lesion placement
or injection of 0.05-0.1 microgram kainic acid, immunoreactivity for all 3
peptides was altered throughout the intact mossy fiber system, bilaterally,
but in distinctly different ways: enkephalin immunoreactivity (ENK-I) was
dramatically elevated, dynorphin immunoreactivity was reduced, and CCK
immunoreactivity (CCK- I) was either severely reduced or completely absent
in the mossy fiber system. ENK-I was also clearly increased in other areas,
including the lateral septum, the entorhinal cortex, and within the
entorhinal (perforant path) efferents to temporal hippocampus. In contrast,
the loss of CCK seemed restricted to the mossy fiber system in that
immunostaining appeared normal in scattered hippocampal perikarya, within
the dentate gyrus commissural system, as well as within other limbic
structures. Four days after injections of 0.2 or 0.25 microgram kainic
acid, mossy fiber ENK-I was greatly elevated, dynorphin immunoreactivity
was reduced, but, unlike the situation with lower kainic acid doses, CCK-I
was only modestly reduced in the mossy fibers and was clearly reduced in
other hippocampal systems as well. These data indicate that epileptiform
physiological activity differentially affects the regulation of 3
neuroactive peptides contained within the hippocampal mossy fiber system
and suggest a mechanism through which seizurelike episodes can have a
lasting influence on the operation of specific hippocampal circuitries.
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