Mossy fiber synaptic reorganization in the epileptic human temporal lobe

Abstract

The distribution of the mossy fiber synaptic terminals was examined using the Timm histochemical method in surgically excised hippocampus and dentate gyrus from patients who underwent lobectomy of the anterior part of the temporal lobe for refractory partial complex epilepsy. The dentate gyrus of epileptic patients demonstrated intense Timm granules and abundant mossy fiber synaptic terminals in the supragranular region and the inner molecular layer. In contrast, the dentate gyrus of presenescent nonepileptic primates demonstrated no Timm granules in the supragranular region. In nonepileptic senescent primates, occasional very sparse supragranular Timm granules were results are morphological evidence of mossy fiber synaptic reorganization in the temporal lobe of epileptic humans, and suggest the intriguing possibility that mossy fiber sprouting and synaptic reorganization induced by repeated partial complex seizures may play a role in human epilepsy.

Studies of stimulus parameters for seizure disruption using neural network simulations

“…Increasing the total number of connections results in higher frequency behaviour, and greater numbers of cells undergoing action potentials at any given time point. One interpretation for this increase in connectivity could be the axonal branch sprouting behaviour that is observed in human and animal models in both neocortex and mesial temporal structures (Sutula 2002;Longo et al 2003;Vijayalakshmi et al 2005;Sutula et al 1989;Carmichael et al 2001). Future studies of epileptic foci might incorporate isolated regions of higher connectivity representing a seizure focus adjoining regions of less excitable modeled tissue to study the spread of epilepsy into normal brain.…”

Down‐regulation of protein l‐isoaspartyl methyltransferase in human epileptic hippocampus contributes to generation of damaged tubulin

“…Microtubules are very abundant in the brain and tubulin is an in vitro and in vivo substrate of PIMT (Ohta et al 1987;Najbauer et al 1996). Previous studies on human epilepsy have reported mossy fiber synapse reorganization and dendrite swelling due to alteration in the normal arrangement of microtubules in temporal lobe epilepsy (Vaquero et al 1982;Sutula et al 1989). In addition, the pyramidal neurons of PIMT-/-mice show abnormal dendrite arborization and microtubule disorganization (Yamamoto et al 1998).…”

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.…”

“…Timm staining is used to visualize mossy fiber reorganization in the inner molecular layer of dentate gyrus that accompanies epileptogenesis (Sutula et al, 1989;Cavazos et al, 1991). Rats surviving up to 8 weeks after SE or 10 times constitutive class 5 seizures in kindling were deeply anesthetized by an overdose chloral hydrate and perfused for 2 min with 0.9% NaCl, 5 min with sulfide solution, and 30 min with 4% paraformaldehyde in 0.1 M phosphate buffer, pH 7.4.…”