Programmed cell death in the lithium pilocarpine model: evidence for NMDA receptor and ceramide-mediated mechanisms.
Ceramide is known to induce programmed cell death (PCD) in neural and non-neural tissues and to increase after kainic acid (KA) status epilepticus (SE). Ceramide increases have been shown to depend on NMDA receptor activation in the KA model, but these changes have not been studied in the lithium pilocarpine (LiPC) model. Thus, the purpose of this study was to determine if hippocampal ceramide levels increase after LiPC induced SE and if NMDA receptor blockade prevents PCD and any such ceramide increases. We found that LiPC induced SE resulted in ceramide increases and DNA fragmentation in the hippocampus of adult, P21, and P7 rats. The administration of MK-801, the NMDA receptor antagonist, in adults, 15min prior to pilocarpine, prevented ceramide increases, and DNA fragmentation.
Mikati
Mohamad A
MA
Department of Pediatrics and Adolescent Medicine, American University of Beirut, Faculty of Medicine, Beirut 1107-2020, Lebanon. mamikati@aub.edu.lb
Rizk
Elias
E
El Dada
Shirine
S
Zeinieh
Michele
M
Kurdi
Rana
R
El Hokayem
Jimmy
J
Rahmeh
Amal
A
Koubeissi
Mohamad
M
Kobeissi
Mohamad
M
Azzam
Diana
D
Usta
Julnar
J
El Sabban
Marwan
M
Dbaibo
Ghassan
G
D000818:Animals; D016923:Cell Death / Q000502:physiology*; D002518:Ceramides / Q000378:metabolism*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D007608:Kainic Acid / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D010862:Pilocarpine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism
D002518:Ceramides; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D010862:Pilocarpine; D016291:Dizocilpine Maleate; D008094:Lithium; D007608:Kainic Acid