Abstracts

Mice lacking cellular prion protein (PrPc) are more sensible to seizures induced by four different pharmacological protocols. The hippocampal formation of these animals disclose supragranular mossy fiber sprouting which resembles those observed in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). A variant allele at position 171, absent in controls, was found in heterozygosis (Asn171Ser) in 23% of patients (p[lt] 0.0001). Patients carrying the Asn171Ser variant had a five times higher chance of continuing to have seizures after temporal lobectomy (95% CI 1.65 to 17.33, p = 0.005) than those carrying the normal allele. These findings suggest that the PrPc may be involved with epileptogenesis in MTLE-HS. Here we investigated the immunohistochemical localization of the PrPc in the hippocampus of animals submitted to the pilocarpine model of temporal lobe epilepsy. Status epilepticus (SE) was induced using pilocarpine (300 mg/kg, i.p.) in five different groups of adult Wistar rats. The survival animals ([italic]n[/italic]=3-5animals/group) were sacrificed one hour, 12 hours, 5 days, two months, and four months after the pilocarpine-induced SE for histopathological analysis. The qualitative results were compared among different groups and with the respective saline-injected controls. Brains were processed for Nissl staining, neo-Timm and imunohistochemistry for PrPc. Expression of PrPc differed according to the different phases of the pilocarpine model. In comparison with controls, no significant changes in prion protein expression were found 1 hour after SE. At 12 hours, we observed increased expression of PrPc in neurons of CA1, CA2, and CA3 regions. Neurons of the superficial layers of the neocortex were also intensively labeled. In chronic animals, (2 and 4 months after SE) prion protein expression was found in the fascia dentata inner molecular layer. Adjacent sections revealed a close co-localization with neo-Timm supragranular mossy fiber sprouting. Prion protein is differentially expressed at different phases of the pilocarpine model of epilepsy. Transient expression of prion protein in animals few hours after SE may reflect changes which may render cells more resistant to seizure-induced damage, may be related with apoptosis or may be related with initial phases of neuroplasticity. In the chronic period prion protein is co-expressed in the same regions the mossy fiber sprouting occurs. We are tempting to think that it might be related with epileptogenic processes, neurotransmission or, alternatively, it might be implicated in cellular protection against recurrent seizures. The functional roles of abnormal PrPc expression remain to be solved. (Supported by FAPESP, CAPES, CNPq)