title: The proapoptotic BCL-2 homology domain 3-only protein Bim is not critical for acute excitotoxic cell death.
abstract: Prolonged and repetitive epileptic activity is causally linked to neuronal cell death in the brain and is most marked in vulnerable subfields of the hippocampus. The Bcl-2 family protein Bim, a proapoptotic member of the BCL-2 homology domain 3-only subfamily, has been implicated as an important mediator of neuronal cell damage in various pathological conditions, although its role in epilepsy-associated cell death is not understood. We performed intrahippocampal stereotaxic injections of the glutamate analog kainic acid as an in vivo model of acute excitotoxicity to assess neuronal injury in Bim-deficient and control wild-type mice. A variety of cell death parameters including chromatin condensation, TdT-mediated dUTP nick end labeling, and caspase-3 activity was assessed. We found no differences in the extent of hippocampal neuronal death parameters between the 2 groups. Moreover, electroencephalographic recordings after kainic acid injection revealed indistinguishable patterns of seizure activity in Bim-deficient and wild-type animals. These in vivo and histological data suggest that Bim is not critically involved in excitotoxicity-induced acute neuronal cell injury.
authors.affiliation: Department of Neuropathology, University of Bonn, Medical Center, Bonn, Germany.
authors.forename: Panos
authors.initials: P
authors.lastname: Theofilas
authors.forename: Peter
authors.initials: P
authors.lastname: Bedner
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hüttmann
authors.forename: Martin
authors.initials: M
authors.lastname: Theis
authors.forename: Christian
authors.initials: C
authors.lastname: Steinhäuser
authors.forename: Stephan
authors.initials: S
authors.lastname: Frank
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000502:physiology*; D000072224:Bcl-2-Like Protein 11; D053148:Caspase 3 / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D020287:In Situ Nick-End Labeling / Q000379:methods; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000503:physiopathology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced; D013238:Stereotaxic Techniques; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase; D007608:Kainic Acid