BACKGROUND: Early postnatal exposure to general anesthesia (GA) may be detrimental to brain development, resulting in long-term cognitive impairments. Older literature suggests that in utero exposure of rodents to GA causes cognitive impairments in the first-generation as well as in the second-generation offspring never exposed to GA. Thus, the authors hypothesize that transient exposure to GA during critical stages of synaptogenesis causes epigenetic changes in chromatin with deleterious effects on transcription of target genes crucial for proper synapse formation and cognitive development. They focus on the effects of GA on histone acetyltransferase activity of cAMP-responsive element-binding protein and the histone-3 acetylation status in the promoters of the target genes brain-derived neurotrophic factor and cellular Finkel-Biskis-Jinkins murine sarcoma virus osteosarcoma oncogene (c-Fos) known to regulate the development of neuronal morphology and function. METHODS: Seven-day-old rat pups were exposed to a sedative dose of midazolam followed by combined nitrous oxide and isoflurane anesthesia for 6 h. Hippocampal neurons and organotypic hippocampal slices were cultured in vitro and exposed to GA for 24 h. RESULTS: GA caused epigenetic modulations manifested as histone-3 hypoacetylation (decrease of 25 to 30%, n = 7 to 9) and fragmentation of cAMP-responsive element-binding protein (two-fold increase, n = 6) with 25% decrease in its histone acetyltransferase activity, which resulted in down-regulated transcription of brain-derived neurotrophic factor (0.2- to 0.4-fold, n = 7 to 8) and cellular Finkel-Biskis-Jinkins murine sarcoma virus osteosarcoma oncogene (about 0.2-fold, n = 10 to 12). Reversal of histone hypoacetylation with sodium butyrate blocked GA-induced morphological and functional impairments of neuronal development and synaptic communication. CONCLUSION: Long-term impairments of neuronal development and synaptic communication could be caused by GA-induced epigenetic phenomena.
BACKGROUND: Early postnatal exposure to general anesthesia (GA) may be detrimental to brain development, resulting in long-term cognitive impairments. Older literature suggests that in utero exposure of rodents to GA causes cognitive impairments in the first-generation as well as in the second-generation offspring never exposed to GA. Thus, the authors hypothesize that transient exposure to GA during critical stages of synaptogenesis causes epigenetic changes in chromatin with deleterious effects on transcription of target genes crucial for proper synapse formation and cognitive development. They focus on the effects of GA on histone acetyltransferase activity of cAMP-responsive element-binding protein and the histone-3 acetylation status in the promoters of the target genes brain-derived neurotrophic factor and cellular Finkel-Biskis-Jinkins murine sarcoma virus osteosarcoma oncogene (c-Fos) known to regulate the development of neuronal morphology and function. METHODS: Seven-day-old rat pups were exposed to a sedative dose of midazolam followed by combined nitrous oxide and isoflurane anesthesia for 6 h. Hippocampal neurons and organotypic hippocampal slices were cultured in vitro and exposed to GA for 24 h. RESULTS: GA caused epigenetic modulations manifested as histone-3 hypoacetylation (decrease of 25 to 30%, n = 7 to 9) and fragmentation of cAMP-responsive element-binding protein (two-fold increase, n = 6) with 25% decrease in its histone acetyltransferase activity, which resulted in down-regulated transcription of brain-derived neurotrophic factor (0.2- to 0.4-fold, n = 7 to 8) and cellular Finkel-Biskis-Jinkins murine sarcoma virus osteosarcoma oncogene (about 0.2-fold, n = 10 to 12). Reversal of histone hypoacetylation with sodium butyrate blocked GA-induced morphological and functional impairments of neuronal development and synaptic communication. CONCLUSION: Long-term impairments of neuronal development and synaptic communication could be caused by GA-induced epigenetic phenomena.
Authors: María Pascual; Bruno R Do Couto; Silvia Alfonso-Loeches; Maria A Aguilar; Marta Rodriguez-Arias; Consuelo Guerri Journal: Neuropharmacology Date: 2012-02-11 Impact factor: 5.250
Authors: Justine D Landin; Magdalena Palac; Jenna M Carter; Yvette Dzumaga; Jessica L Santerre-Anderson; Gina M Fernandez; Lisa M Savage; Elena I Varlinskaya; Linda P Spear; Scott D Moore; H Scott Swartzwelder; Rebekah L Fleming; David F Werner Journal: Neuropharmacology Date: 2019-03-26 Impact factor: 5.250
Authors: Omar Hoseá Cabrera; Shawn David O'Connor; Brant Stephen Swiney; Patricia Salinas-Contreras; Francesca Maria Manzella; George Townsend Taylor; Kevin Kiyoshi Noguchi Journal: J Matern Fetal Neonatal Med Date: 2016-12-07
Authors: Srdjan M Joksimovic; Hari Prasad Osuru; Azra Oklopcic; Mark P Beenhakker; Vesna Jevtovic-Todorovic; Slobodan M Todorovic Journal: Mol Neurobiol Date: 2018-01 Impact factor: 5.590
Authors: Richard J Levy; Julie B Herbstman; Zeljko J Bosnjak; Andreas W Loepke; Francis X McGowan Journal: J Neurosurg Anesthesiol Date: 2016-10 Impact factor: 3.956
Authors: William M Jackson; Christy D B Gray; Danye Jiang; Michele L Schaefer; Caroline Connor; Cyrus D Mintz Journal: J Neurosurg Anesthesiol Date: 2016-10 Impact factor: 3.956