کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2036700 1072276 2010 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Caspase-3 Activation via Mitochondria Is Required for Long-Term Depression and AMPA Receptor Internalization
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی، ژنتیک و زیست شناسی مولکولی (عمومی)
پیش نمایش صفحه اول مقاله
Caspase-3 Activation via Mitochondria Is Required for Long-Term Depression and AMPA Receptor Internalization
چکیده انگلیسی

SummaryNMDA receptor-dependent synaptic modifications, such as long-term potentiation (LTP) and long-term depression (LTD), are essential for brain development and function. LTD occurs mainly by the removal of AMPA receptors from the postsynaptic membrane, but the underlying molecular mechanisms remain unclear. Here, we show that activation of caspase-3 via mitochondria is required for LTD and AMPA receptor internalization in hippocampal neurons. LTD and AMPA receptor internalization are blocked by peptide inhibitors of caspase-3 and -9. In hippocampal slices from caspase-3 knockout mice, LTD is abolished whereas LTP remains normal. LTD is also prevented by overexpression of the anti-apoptotic proteins XIAP or Bcl-xL, and by a mutant Akt1 protein that is resistant to caspase-3 proteolysis. NMDA receptor stimulation that induces LTD transiently activates caspase-3 in dendrites, without causing cell death. These data indicate an unexpected causal link between the molecular mechanisms of apoptosis and LTD.

Graphical AbstractFigure optionsDownload high-quality image (302 K)Download as PowerPoint slideHighlights
► Caspase-3 inhibitor, Bcl-xL or XIAP overexpression block long-term depression
► LTD is abolished in caspase-3 knockout mice, whereas LTP is intact
► LTD-like stimulation induces transient activation of caspase-3
► A mutant Akt1 resistant to caspase-3 cleavage prevents LTD

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 141, Issue 5, 28 May 2010, Pages 859–871
نویسندگان
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