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Anesthetic Sevoflurane Causes Rho-Dependent Filopodial Shortening in Mouse Neurons
- Source :
- PLoS ONE, Vol 11, Iss 7, p e0159637 (2016), PLoS ONE
- Publication Year :
- 2016
- Publisher :
- Public Library of Science (PLoS), 2016.
-
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.
- Subjects :
- rho GTP-Binding Proteins
Pathology
Dendritic spine
RHOA
Physiology
Pyridines
Kinase Inhibitors
Synaptogenesis
Dendritic spine morphogenesis
lcsh:Medicine
Nervous System
Microtubules
Biochemistry
Hippocampus
0302 clinical medicine
030202 anesthesiology
Animal Cells
Anesthesiology
Medicine and Health Sciences
Anesthesia
Pseudopodia
Enzyme Inhibitors
lcsh:Science
Cytoskeleton
Neurons
Multidisciplinary
Pharmaceutics
Drugs
Cell biology
Electrophysiology
Female
Cellular Types
Anatomy
Cellular Structures and Organelles
Filopodia
Research Article
Methyl Ethers
medicine.medical_specialty
Imaging Techniques
Cell Survival
Dendritic Spines
Neurophysiology
Biology
Research and Analysis Methods
03 medical and health sciences
Sevoflurane
Drug Therapy
Cellular neuroscience
Fluorescence Imaging
medicine
Pain Management
Animals
Protein Kinase Inhibitors
Anesthetics
Pharmacology
Neuropeptides
lcsh:R
Biology and Life Sciences
Cell Biology
Neuronal Dendrites
Amides
Actins
Mice, Inbred C57BL
Rho kinase inhibitor
Cellular Neuroscience
Synapses
biology.protein
Enzymology
lcsh:Q
030217 neurology & neurosurgery
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 11
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....6e37b6a6be9a0957bbf68c2cdd8cbbff