Details

Autor(en) / Beteiligte

• Thal, Simone E.
• Zhu, Changlian
• Thal, Serge C.
• Blomgren, Klas
• Plesnila, Nikolaus

Titel

Role of apoptosis inducing factor (AIF) for hippocampal neuronal cell death following global cerebral ischemia in mice

Ist Teil von

• Neuroscience letters, 2011-07, Vol.499 (1), p.1-3

Ort / Verlag

Shannon: Elsevier Ireland Ltd

Erscheinungsjahr

2011

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• ► Apoptosis-inducing factor (AIF) translocates from mitochondria to the nucleus in dying neurons following global cerebral ischemia. ► In mice with low AIF expression hippocampal neuronal cell death is reduced by over 60%. ► Current findings suggest that AIF is a significant mediator of neuronal cell death in a model of cardiac-arrest-induced brain injury. The molecular mechanisms of neuronal cell death following circulatory arrest are still not fully understood. In the current study we investigated the role of apoptosis-inducing factor (AIF), a major caspase-independent mitochondrial cell death protein, for neuronal cell death following global cerebral ischemia (GCI). C57/Bl6 or low AIF expressing Harlequin mutant mice (AIF low) and their wild-type littermates were subjected to 10 min of GCI. DNA damage, nuclear pathology, and localization of AIF were investigated 6, 24, and 72 h after GCI by TUNEL and DAPI staining, and immunohistochemistry, respectively. Cell death of hippocampal CA1 neurons following GCI was associated with nuclear translocation of AIF, nuclear pyknosis, and DNA fragmentation, i.e. ∼80% of all TUNEL-positive neurons had nuclear AIF staining. In AIF low mice neuronal cell loss was reduced by 60% ( p < 0.02). The current experiments suggest that AIF-mediated signaling represents a novel mechanism of neuronal cell death following GCI.