General anesthesia activates BDNF-dependent neuroapoptosis in the developing rat brain |
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Authors: | Lucy X Lu Jun-Heum Yon Lisa B Carter Vesna Jevtovic-Todorovic |
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Institution: | (1) Department of Anesthesiology, University of Virginia Health System, P.O. Box 800710, Charlottesville, VA 22908, USA;(2) Department of Anesthesiology, Sanggye Paik Hospital, Inje University, Seoul, Korea |
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Abstract: | Brain-derived neurotrophic factor (BDNF) is important in supporting neuronal development. BDNF imbalance due to excessive
neuronal inhibition can result in the apoptotic degeneration of developing neurons. Since general anesthetics cause profound
depression of neuronal activity and are known to induce widespread degeneration in the developing brain, we studied their
potential to activate BDNF-mediated developmental neuroapoptosis. When P7 rats (at the peak of brain development) were exposed
to a commonly-used and highly pro-apoptotic anesthesia protocol (midazolam, isoflurane, nitrous oxide) for a period of 2,
4 or 6 h, we found that anesthesia modulates the key steps in BDNF-activated apoptotic cascade in two of the most vulnerable
brain regions—cerebral cortex and thalamus in time-dependent fashion by activating both Trk-dependent (in thalamus) and Trk-independent
p75NTR dependent (in cerebral cortex) neurotrophic pathways. β-estradiol, a sex hormone that upregulates the protein levels of the
activated Akt, protects against anesthesia-induced neuroapoptosis. |
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Keywords: | Akt Caspase Ceramide Neurotoxicity Neurotrophins p75NTR Synaptogenesis β estradiol |
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