title: Influence of neonatal sevoflurane exposure on nerve development-related microRNAs and behavior of rats.
abstract: Commonly used anesthetics adversely affect the developing brain, but the mechanisms remain unknown. We previously showed that the expressions of microRNAs (miRNAs) in major organs are affected by anesthetics. Therefore, we used TaqMan low-density array (TLDA) to analyze gene expression in the hippocampus of neonatal rats exposed to sevoflurane and performed behavioral tests after they reached adulthood to evaluate cognitive and memory function. Rat male pups at postnatal day 7 were exposed to 1.9% sevoflurane for 3 h, and the hippocampus-miRNA expression profile on postnatal day 8 was determined. Open field and fear conditioning tests conducted during postnatal weeks 7 and 8 indicated that sevoflurane-exposed rats, but not controls, exhibited anxiety-like disorders. TLDA analysis identified 20 differentially expressed miRNAs, which were not shared between postnatally and maturely sevoflurane-exposed rats. The level of rno-miR-632, which targets brain-derived neurotrophic factor and calcium channel, voltage-dependent, alpha 2/delta subunit 2, increased by 10-fold, indicating that exposure to sevoflurane during early neural development alters hippocampus-miRNA expression and may induce subsequent behavioral disorders.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School.
authors.forename: Saiko
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Masashi
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nagano
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Sakamoto
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001008:Anxiety Disorders / Q000139:chemically induced / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D000077149:Sevoflurane
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C478374:Cacna2d2 protein, rat; D015220:Calcium Channels; D008738:Methyl Ethers; D035683:MicroRNAs; D000077149:Sevoflurane