Apoptosis of hippocampal neurons after amygdala kindled seizures.
Seizure-induced neuronal damage may involve both excitotoxic and apoptotic (programmed cell death) mechanisms. In the present study, we used an amygdala kindled seizure model to study whether apoptotic cell death occurs. To evaluate apoptosis, we counted the numbers of cells that had DNA fragments labeled at the 3' end with digoxigenin using terminal transferase (ApopTag, Oncor). Additionally, the expression of Bax and Bcl-2, two genes associated with apoptotic cell death, was also measured following kindled seizures. We found that the number of ApopTag-positive cells in the hippocampus increased 30.4% after one kindled seizure and 82.5% after 20 seizures compared to sham controls. The ApopTag-labeled cells could be mainly interneurons of the hippocampal formation, although additional studies are required. Preferential vulnerability of inhibitory interneurons is consistent with previous studies on seizure-induced cell loss. These results, coupled with our findings that the ratio of Bax/Bcl-2 expression is increased in the hippocampus by seizures, suggest that apoptosis of hippocampal interneurons may lead to dysinhibition in the hippocampus and increased seizure susceptibility.
Zhang
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LX
Biological Psychiatric Branch, NIMH, Bldg 10/Rm 3N212, Bethesda, MD 20982, USA. lzhang@mx3.usuhs.mil
Smith
M A
MA
Li
X L
XL
Weiss
S R
SR
Post
R M
RM
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000473:pathology*; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein