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. Author manuscript; available in PMC: 2017 Jun 1.
Published in final edited form as: Anesthesiology. 2016 Jun;124(6):1311–1327. doi: 10.1097/ALN.0000000000001111

Figure 12. Proposed cascade of epigenetic events responsible for anesthesia-induced neurotoxicity during critical stages of synaptogenesis.

Figure 12

Anesthesia promotes excessive cAMP-responsive element binding protein (CBP) degradation (fragmentation from 270 kDa to 148 kDa) thus down-regulating full length CBP protein with consequent decrease of its histone acetylase (HAT) activity. This decreased HAT activity, in turn, causes histone-3 hypoacetylation, an epigenetic change that leads to more condensed chromatin structure less conducive to transcription of the target genes brain-derived neurotrophic factor (BDNF) and c-Fos. BDNF and c-Fos are critical for neuronal morphological development. An impairment in proper dendritic arborization leads to impaired neuronal connectivity resulting in faulty formation of neuronal circuities and compromised synaptic neurotransmission.