Document Detail


Preservation of mitochondrial integrity and energy metabolism during experimental status epilepticus leads to neuronal apoptotic cell death in the hippocampus of the rat.
MedLine Citation:
PMID:  19375359     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Status epilepticus results in mitochondrial damage or dysfunction and preferential neuronal cell loss in the hippocampus. Since a critical determinant of the eventual cell death fate resides in intracellular ATP concentration, we investigated whether mitochondrial integrity and level of energy metabolism are related with apoptotic cell death in specific hippocampal neuronal populations. A kainic acid (KA)-induced experimental temporal lobe status epilepticus model was used. Qualitative and quantitative analysis of DNA fragmentation, TUNEL immunohistochemistry, double immunofluorescence staining for activated caspase-3, electron microscopy or measurement of ATP level in the bilateral hippocampus was carried out 1, 3 or 7 days after microinjection unilaterally of a low dose of KA (0.5 nmol) into the CA3 hippocampal subfield. Characteristic biochemical (DNA fragmentation), histochemical (TUNEL or activated caspase-3 staining) or ultrastructural (electron microscopy) features of apoptotic cell death were presented bilaterally in the hippocampus 7 days after the elicitation of sustained hippocampal seizure activity by microinjection of KA into the unilateral CA3 subfield. At the same time, CA3 or CA1 subfield on either side manifested a maintained ATP level; alongside relatively intact mitochondria, rough endoplasmic reticulum, Golgi apparatus or cytoplasmic membrane in hippocampal neurons that exhibited ultrastructural features of apoptotic cell death. Our results demonstrated that preserved mitochondrial ultrastructural integrity and maintained energy metabolism during experimental temporal lobe status epilepticus is associated specifically with apoptotic, not necrotic, cell death in hippocampal CA3 or CA1 neurons.
Authors:
Yao-Chung Chuang; Jui-Wei Lin; Shang-Der Chen; Tsu-Kung Lin; Chia-Wei Liou; Cheng-Hsien Lu; Wen-Neng Chang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-17
Journal Detail:
Title:  Seizure : the journal of the British Epilepsy Association     Volume:  18     ISSN:  1532-2688     ISO Abbreviation:  Seizure     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-08     Completed Date:  2009-09-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9306979     Medline TA:  Seizure     Country:  England    
Other Details:
Languages:  eng     Pagination:  420-8     Citation Subset:  IM    
Affiliation:
Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan. ycchuang@adm.cgmh.org.tw
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Analysis of Variance
Animals
Apoptosis / drug effects,  physiology*
Caspase 3 / metabolism
DNA Fragmentation / drug effects
Disease Models, Animal
Energy Metabolism / physiology*
Excitatory Amino Acid Agonists / pharmacology
Hippocampus / drug effects,  pathology*
In Situ Nick-End Labeling / methods
Kainic Acid / pharmacology
Male
Microscopy, Electron, Transmission / methods
Mitochondria / pathology*,  ultrastructure
Neurons / drug effects,  pathology*,  ultrastructure
Phosphopyruvate Hydratase / metabolism
Rats
Rats, Sprague-Dawley
Status Epilepticus* / chemically induced,  metabolism,  pathology,  physiopathology
Time Factors
Chemical
Reg. No./Substance:
0/Excitatory Amino Acid Agonists; 487-79-6/Kainic Acid; 56-65-5/Adenosine Triphosphate; EC 3.4.22.-/Caspase 3; EC 4.2.1.11/Phosphopyruvate Hydratase

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