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Journal of Neuroscience, Vol 10, 267-282, Copyright © 1990 by Society for Neuroscience
Altered patterns of dynorphin immunoreactivity suggest mossy fiber reorganization in human hippocampal epilepsy
CR Houser, JE Miyashiro, BE Swartz, GO Walsh, JR Rich and AV Delgado-Escueta
California Comprehensive Epilepsy Program, Veterans Administration Medical Center, West Los Angeles, California.
Dynorphin A(1-17), an opioid peptide that is normally present in the
hippocampal mossy fiber system, was localized immunocytochemically in the
hippocampal formation of control autopsy and temporal lobe epilepsy (TLE)
specimens. In control tissue, dynorphin-like immunoreactive (Dyn- IR)
structures were confined to the mossy fiber path and were most highly
concentrated in the polymorph (hilar) region of the dentate gyrus. Very few
Dyn-IR structures were present in the molecular and granule cell layers of
the dentate gyrus. In contrast, in all TLE specimens, Dyn-IR elements were
present in these layers. The extent of aberrant staining varied among the
TLE specimens, and 2 major patterns were observed. The first was a
relatively wide band of reaction product in the inner one-third to
one-fourth of the molecular layer (8 cases), and the second was a more
limited distribution of immunoreactive fibers and presumptive terminals in
the granule cell and immediately adjacent supragranular regions (2 cases).
The extent of aberrant Dyn-IR structures appeared to be related to the
amount of cell loss in the polymorph and CA3 fields and to dispersion of
the granule cell somata. Specimens processed with the Timm's sulfide silver
method for heavy metals provided independent evidence for the distribution
of mossy fibers. In both control and TLE specimens, the patterns of
labeling were virtually identical to those of dynorphin localization. These
findings suggest that sprouting of mossy fibers or their axon collaterals
has occurred in hippocampal epilepsy and that the reorganized fibers
contain at least one of the neuropeptides that are normally present in this
system. Such fibers could form recurrent excitatory circuits and contribute
to synchronous firing and epileptiform activity, as suggested in studies of
experimental models of epilepsy.
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