Abstracts

The neural cell adhesion molecule (NCAM) is an important regulator of cell-cell interactions involved in neuritic growth, cell migration, and synaptic plasticity. In the adult brain polysialylation of NCAM is predominantly mediated by polysialyltransferase ST8SiaIV. This coupling of polysialic acid (PSA) to NCAM by ST8SiaIV seems to be a presupposition for different forms of plasticity. Seizure activity proved to enhance polysialylation of NCAM. Aim of the present study was to identify the consequences of a deficiency of polysialylation on seizure susceptibility. ST8SiaIV knockout mice and wildtype litter mates were used for the experiments. Seizures were induced by the chemoconvulsants pentylenetetrazole (i.v. infusion), pilocarpine (fractionated administration of 100 mg/kg i.p. every 30 min until the first seizure), or kainic acid (25 mg/kg i.p.). Furthermore groups of animals were kindled by twice daily stimulation via corneal electrodes. ST8SiaIV knockout mice did not differ from wildtype mice with regard to kindling progression. Furthermore there were only slight differences in the amount of pentylenetetrazole required to induce different seizure stages in both groups of mice.
Following administration of kainic acid, about the same percentage of animals developed a status epilepticus. However, the latency to the first generalized seizure was significantly shortened in ST8SiaIV deficient mice. Twentyeight percent of the ST8SiaIV knockout mice died during status epilepticus, whereas none of the wildtype animals died. About the same amount of pilocarpine was necessary to induce generalized seizure activity in knockout mice and wildtype mice. However, following pilocarpine administration significantly more animals died in the group of ST8SiaIV knockout mice. The results indicate that genetic deficiency of ST8SiaIV does not change the susceptibility to the induction of acute seizures. However, during ongoing seizure activity lack of ST8SiaIV predisposes to death. Thus, the deficiency in polysialylation may result in the loss of seizure-induced PSA-dependent plastic changes, which are capable of mediating endogenous protection to seizure-associated damage. In future studies, we will investigate the impact of ST8SiaIV deficiency on seizure-induced plasticity. (Supported by RGS: Deutsche Forschungsgemeinschaft GE 801/3-3.)