Abstracts

Cell adhesion molecules such as the neural cell adhesion molecule (NCAM) and especially its polysialylated form (PSA-NCAM) have been demonstrated to be involved in the regulation of neural plasticity, e.g. cell migration, neurite growth, and synaptic plasticity. The polysialylation of NCAM seems to be a presupposition for different forms of synaptic plasticity. To investigate the impact of PSA-dependant plasticity on seizure susceptibility and epileptogenesis, we enzymatically removed polysialic acid (PSA) from NCAM. Following i.c.v. administration of neuraminidase (endo-N) in male Sprague-Dawley rats, we studied the effect in two electrically-induced epilepsy models, the amygdala-kindling model and a post-status epilepticus model. In the amygdala-kindling model animals were kindled by daily constant current electrostimulation. In the post-status epilepticus model a self-sustained status epilepticus was induced by prolonged electrostimulation of the basolateral amygdala. As a consequence of the status epilepticus, spontaneous seizures occur after a latency period of several weeks in the majority of animals. Six weeks after status epilepticus spontaneous seizures were monitored during a period of two weeks by a 24 hour video and EEG recording. The results indicate that endo-N treatment decreases the initial afterdischarge threshold (ADT), but has no effect on the post ADT in the amygdala-kindling model. The post ADT was lowered as compared to the initial ADT in control rats, but not in the endo-N treated group. Although the seizure threshold was decreased, kindling progression was not influenced.
In the post-status epilepticus model, endo-N treatment significantly reduced the severity of the self-sustained status epilepticus. However, the treatment had no consequence on the development of spontaneous seizures. Reduction of the initial ADT in the amygdala-kindling model indicates a proconvulsive effect of the PSA degradation. In contrast, reduced severity of the self-sustained status epilepticus reveals anticonvulsant properties of the de-polysialylation of NCAM. Lack of differences in kindling progression and in epileptogenesis following status epilepticus indicate that PSA-dependent plasticity does not critically influence epileptogenesis. At present we perform immunhistological investigations, which aim to identify the impact of endo-N treatment on kindling-associated neural plasticity and status epilepticus-induced neural plasticity. (Supported by Deutsche Forschungsgemeinschaft DFG-GE 801/3-3; Mu 1774/2-1.)