Abstracts

Rationale: The ciliary neurotrophic growth factor (CNTF) is a neurotrophic cytokine which plays an important role in the development of neuronal cells. CNTF protects neurons from glutamate excitotoxicity and improves learning and memory. Therefore, it is of specific interest to determine whether the CNTF-derived peptide Cintrofin can influence epileptogenesis, neuronal alterations and associated behavioral deficits in a chronic epilepsy model. Methods: Male NMRI mice received either Cintrofin or vehicle-injections (2 mg/kg, 10 mg/kg s.c.) once daily for 3 weeks in the BLA-kindling model. The impact of Cintrofin on seizure severity was investigated. Furthermore, the development of kindling-associated alterations in behavior and on neuronal alterations was analyzed Results: Cintrofin did not affect the progression of seizure severity in the amygdala-kindling model. As a consequence of kindling, locomotion in the open field and the elevated-plus-maze were significantly increased. Cintrofin did not attenuate these behavioral alterations. On the other hand, time spent in the inner zone of the open field was significantly increased in Cintrofin-treated control animals. In addition, Cintrofin significantly reduced the number of persistent basal dendrites in kindled animals. Conclusions: In summary, the results argue against a disease-modifying and antiepileptogenic effect of the CNTF-derived peptide mimetic Cintrofin. However, Cintrofin decreases seizure-associated alterations in hippocampal neurogenesis such as persistence of basal dendrites. Acknowledgement: We thank Marion Fisch and Angela Vicidomini for their excellent technical assistance. The authors are grateful for support by a grant from the Deutsche Forschungsgemeinschaft (DFG FOR1103;PO-681/5-1)