dc.contributor.author | Zimering, Jeffrey H. | en_US |
dc.contributor.author | Dong, Yuanlin | en_US |
dc.contributor.author | Fang, Fang | en_US |
dc.contributor.author | Huang, Lining | en_US |
dc.contributor.author | Zhang, Yiying | en_US |
dc.contributor.author | Xie, Zhongcong | en_US |
dc.date.accessioned | 2016-10-11T20:26:42Z | |
dc.date.issued | 2016 | en_US |
dc.identifier.citation | Zimering, Jeffrey H., Yuanlin Dong, Fang Fang, Lining Huang, Yiying Zhang, and Zhongcong Xie. 2016. “Anesthetic Sevoflurane Causes Rho-Dependent Filopodial Shortening in Mouse Neurons.” PLoS ONE 11 (7): e0159637. doi:10.1371/journal.pone.0159637. http://dx.doi.org/10.1371/journal.pone.0159637. | en |
dc.identifier.issn | 1932-6203 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:29002530 | |
dc.description.abstract | Early postnatal anesthesia causes long-lasting learning and memory impairment in rodents, however, evidence for a specific neurotoxic effect on early synaptogenesis has not been demonstrated. Drebrin A is an actin binding protein whose localization in dendritic protrusions serves an important role in dendritic spine morphogenesis, and is a marker for early synaptogenesis. We therefore set out to investigate whether clinically-relevant concentrations of anesthetic sevoflurane, widely- used in infants and children, alters dendritic morphology in cultured fetal day 16 mouse hippocampal neurons. After 7 days in vitro, mouse hippocampal neurons were exposed to four hours of 3% sevoflurane in 95% air/5% CO2 or control condition (95% air/5% CO2). Neurons were fixed in 4% paraformaldehyde and stained with Alexa Fluor555-Phalloidin, and/or rabbit anti-mouse drebrin A/E antibodies which permitted subcellular localization of filamentous (F)-actin and/or drebrin immunoreactivity, respectively. Sevoflurane caused acute significant length-shortening in filopodia and thin dendritic spines in days-in-vitro 7 neurons, an effect which was completely rescued by co-incubating neurons with ten micromolar concentrations of the selective Rho kinase inhibitor Y27632. Filopodia and thin spine recovered in length two days after sevoflurane exposure. Yet cluster-type filopodia (a precursor to synaptic filopodia) were persistently significantly decreased in number on day-in-vitro 9, in part owing to preferential localization of drebrin immunoreactivity to dendritic shafts versus filopodial stalks. These data suggest that sevoflurane induces F-actin depolymerization leading to acute, reversible length-shortening in dendritic protrusions through a mechanism involving (in part) activation of RhoA/Rho kinase signaling and impairs localization of drebrin A to filopodia required for early excitatory synapse formation. | en |
dc.language.iso | en_US | en |
dc.publisher | Public Library of Science | en |
dc.relation.isversionof | doi:10.1371/journal.pone.0159637 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956198/pdf/ | en |
dash.license | LAA | en_US |
dc.subject | Biology and Life Sciences | en |
dc.subject | Cell Biology | en |
dc.subject | Cellular Types | en |
dc.subject | Animal Cells | en |
dc.subject | Neurons | en |
dc.subject | Neuroscience | en |
dc.subject | Cellular Neuroscience | en |
dc.subject | Neuronal Dendrites | en |
dc.subject | Medicine and Health Sciences | en |
dc.subject | Anesthesiology | en |
dc.subject | Anesthesia | en |
dc.subject | Pharmaceutics | en |
dc.subject | Drug Therapy | en |
dc.subject | Anatomy | en |
dc.subject | Nervous System | en |
dc.subject | Synapses | en |
dc.subject | Physiology | en |
dc.subject | Electrophysiology | en |
dc.subject | Neurophysiology | en |
dc.subject | Pharmacology | en |
dc.subject | Drugs | en |
dc.subject | Anesthetics | en |
dc.subject | Pain Management | en |
dc.subject | Imaging Techniques | en |
dc.subject | Fluorescence Imaging | en |
dc.subject | Cellular Structures and Organelles | en |
dc.subject | Cytoskeleton | en |
dc.subject | Microtubules | en |
dc.subject | Biochemistry | en |
dc.subject | Enzymology | en |
dc.subject | Enzyme Inhibitors | en |
dc.subject | Kinase Inhibitors | en |
dc.title | Anesthetic Sevoflurane Causes Rho-Dependent Filopodial Shortening in Mouse Neurons | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | PLoS ONE | en |
dash.depositing.author | Zhang, Yiying | en_US |
dc.date.available | 2016-10-11T20:26:42Z | |
dc.identifier.doi | 10.1371/journal.pone.0159637 | * |
dash.contributor.affiliated | Zhang, Yiying | |
dash.contributor.affiliated | Xie, Zhongcong | |