Elevated preoptic brain activity in zebrafish glial glycine transporter mutants is linked to lethargy-like behaviors and delayed emergence from anesthesia
| Autor: | Stephan Züchner, Owen Randlett, Steven A. Sloan, Julia E. Dallman, Matthew J. Stark, Qing Cheng Meng, Max B. Kelz, Florian Engert, Qing Yan, Richard Bindernagel, Michael J. Venincasa, Sheyum Syed, Elena Buglo, Sureni Sumathipala |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Hyperglycinemia Nonketotic Science Mutant Glycine Gene Expression Anesthesia General Glycine encephalopathy Delayed Emergence from Anesthesia Article Glycine transporter Animals Genetically Modified 03 medical and health sciences eIF-2 Kinase 0302 clinical medicine Glycine Plasma Membrane Transport Proteins medicine Genetics Premovement neuronal activity Animals Ketamine Aminobenzoates Zebrafish Propofol Anesthetics Neurons Multidisciplinary biology Zebrafish Proteins medicine.disease biology.organism_classification Preoptic Area Disease Models Animal 030104 developmental biology Anesthesia Medicine 030217 neurology & neurosurgery Craniotomy Locomotion Neurological disorders medicine.drug Neuroscience |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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