文章基本信息

标题：Elevated preoptic brain activity in zebrafish glial glycine transporter mutants is linked to lethargy-like behaviors and delayed emergence from anesthesia
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作者：Michael J. Venincasa ; Owen Randlett ; Sureni H. Sumathipala 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2021
卷号：11
期号：1
页码：3148
DOI：10.1038/s41598-021-82342-w
出版社：Springer Nature
摘要：Abstract Delayed emergence from anesthesia was previously reported in a case study of a child with Glycine Encephalopathy. To investigate the neural basis of this delayed emergence, we developed a zebrafish glial glycine transporter ( glyt1 − / − ) mutant model. We compared locomotor behaviors; dose–response curves for tricaine, ketamine, and 2,6-diisopropylphenol (propofol); time to emergence from these anesthetics; and time to emergence from propofol after craniotomy in glyt1−/− mutants and their siblings. To identify differentially active brain regions in glyt1−/− mutants, we used pERK immunohistochemistry as a proxy for brain-wide neuronal activity. We show that glyt1−/− mutants initiated normal bouts of movement less frequently indicating lethargy-like behaviors. Despite similar anesthesia dose–response curves, glyt1−/− mutants took over twice as long as their siblings to emerge from ketamine or propofol, mimicking findings from the human case study. Reducing glycine levels rescued timely emergence in glyt1−/− mutants, pointing to a causal role for elevated glycine. Brain-wide pERK staining showed elevated activity in hypnotic brain regions in glyt1−/− mutants under baseline conditions and a delay in sensorimotor integration during emergence from anesthesia. Our study links elevated activity in preoptic brain regions and reduced sensorimotor integration to lethargy-like behaviors and delayed emergence from propofol in glyt1−/− mutants.
其他摘要：Abstract Delayed emergence from anesthesia was previously reported in a case study of a child with Glycine Encephalopathy. To investigate the neural basis of this delayed emergence, we developed a zebrafish glial glycine transporter ( glyt1 − / − ) mutant model. We compared locomotor behaviors; dose–response curves for tricaine, ketamine, and 2,6-diisopropylphenol (propofol); time to emergence from these anesthetics; and time to emergence from propofol after craniotomy in glyt1−/− mutants and their siblings. To identify differentially active brain regions in glyt1−/− mutants, we used pERK immunohistochemistry as a proxy for brain-wide neuronal activity. We show that glyt1−/− mutants initiated normal bouts of movement less frequently indicating lethargy-like behaviors. Despite similar anesthesia dose–response curves, glyt1−/− mutants took over twice as long as their siblings to emerge from ketamine or propofol, mimicking findings from the human case study. Reducing glycine levels rescued timely emergence in glyt1−/− mutants, pointing to a causal role for elevated glycine. Brain-wide pERK staining showed elevated activity in hypnotic brain regions in glyt1−/− mutants under baseline conditions and a delay in sensorimotor integration during emergence from anesthesia. Our study links elevated activity in preoptic brain regions and reduced sensorimotor integration to lethargy-like behaviors and delayed emergence from propofol in glyt1−/− mutants.