Antiepileptic Drug-Induced Apoptosis Was Prevented by L-Type Calcium Channel Activator in Cultured Rat Cortical CellsReport as inadecuate




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Experimental data have shown that antiepileptic drugs cause neurodegeneration in developing rats. Valproate VPA is the drug of choice in primary generalized epilepsies, and carbamazepine CBZ is one of the most prescribed drugs in partial seizures. These drugs block sodium channels, thereby reducing sustained repetitive neuronal firing. The intracellular mechanisms whereby AEDs induce neuronal cell death are unclear. We examined whether AEDs induce apoptotic cell death in cultured cortical cells and whether calcium ions are involved in the AED-induced cell death. VPA and CBZ increased apoptotic cell death and induced morphological changes that were characterized by cell shrinkage and nuclear condensation or fragmentation. Incubation of cortical cultures with VPA or CBZ decreased phospho-Akt levels. CBZ decreased the intracellular calcium levels. On the other hand, FPL64176, an L-type calcium channel activator, increased the intracellular calcium levels and prevented the AED-induced apoptosis. Glycogen synthase kinase-3 inhibitors, such as alsterpaullone and azakenpaullone, prevented the AED-induced apoptosis. These results suggest that intracellular calcium level changes are associated with AEDs and apoptosis and that the activation of glycogen synthase kinase-3 is involved in the death of rat cortical neurons.

KEYWORDS

Antiepileptic Drug, Valproate, Carbamazepine, L-Type Calcium Channel, Glycogen Synthase Kinase-3, Apoptosis

Cite this paper

Takadera, T. , Aoki, M. and Nakanishi, N. 2017 Antiepileptic Drug-Induced Apoptosis Was Prevented by L-Type Calcium Channel Activator in Cultured Rat Cortical Cells. Open Journal of Apoptosis, 6, 17-27. doi: 10.4236-ojapo.2017.62002.





Author: Tsuneo Takadera, Masashi Aoki, Naruto Nakanishi

Source: http://www.scirp.org/



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