Altered patterns of dynorphin immunoreactivity suggest mossy fiber reorganization in human hippocampal epilepsy

Abstract

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.

A morphologically distinct granule cell type in the dentate gyrus of the red fox correlates with adult hippocampal neurogenesis

“…Similar to other species, dynorphin marks the terminal fields of the dentate granule cells in the hilus and mossy fiber zone of the hippocampus (Drake et al, 1994;Khachaturian et al, 1982). The staining pattern in the polymorphic cell layer corresponds to that seen in the human hippocampus (Houser et al, 1990).…”

Differential Roles of NR2A- and NR2B-Containing NMDA Receptors in Activity-Dependent Brain-Derived Neurotrophic Factor Gene Regulation and Limbic Epileptogenesis

“…Selective effects of NR2A and NR2B antagonists on mossy fiber sprouting Activation of NMDARs has been implicated in seizure-induced mossy fiber sprouting, which is also a feature of human limbic epilepsy (Sutula et al, 1989;Houser et al, 1990;Sutula et al, 1996). It is thus of interest to determine whether the selective impediment of epileptogenesis by NR2A antagonist is also reflected in seizure-induced mossy fiber sprouting, which normally occurs a few weeks after SE.…”

Transcortical Selective Amygdalohippocampectomy in Temporal Lobe Epilepsy

“…[10][11][12] More recent work has shed light on the basic physiopathological mechanisms responsible for mesio-temporal epilepsy. [13][14][15][16][17][18][19][20] Studies on mesio-temporal kindling have brought further ABSTRACT: Numerous studies of the electrophysiology and neuropathology of temporal lobe epilepsy have demonstrated the mesial temporal structures to be the site of seizure origin in the majority of cases. This is the rationale for a transcortical selective approach, first introduced by Niemeyer, for removal of the hippocampus and amygdala.…”