TY - JOUR
T1 - Programmed cell death in the lithium pilocarpine model
T2 - Evidence for NMDA receptor and ceramide-mediated mechanisms
AU - Mikati, Mohamad A.
AU - Rizk, Elias
AU - El Dada, Shirine
AU - Zeinieh, Michele
AU - Kurdi, Rana
AU - El Hokayem, Jimmy
AU - Rahmeh, Amal
AU - Kobeissi, Mohamad
AU - Azzam, Diana
AU - Usta, Julnar
AU - El Sabban, Marwan
AU - Dbaibo, Ghassan
N1 - Funding Information:
We thank the staff of the animal care facility at the American University of Beirut for their support: Dr. Rosemarie Jaouhari, Mr. Hussein Younis, Mrs. Suha Diab, Mr. Adib Abi Mahmoud, and Mr. Badr Shakaroun. This work was supported by grants form the Lebanese National Council for Scientific Research, Diana Tamari Sabbagh, and URB.
PY - 2008/9
Y1 - 2008/9
N2 - 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, 15 min prior to pilocarpine, prevented ceramide increases, and DNA fragmentation.
AB - 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, 15 min prior to pilocarpine, prevented ceramide increases, and DNA fragmentation.
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U2 - 10.1016/j.braindev.2008.01.002
DO - 10.1016/j.braindev.2008.01.002
M3 - Article
C2 - 18295995
AN - SCOPUS:47149106104
SN - 0387-7604
VL - 30
SP - 513
EP - 519
JO - Brain and Development
JF - Brain and Development
IS - 8
ER -