Abstract SNACC-65

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Toward a mechanism underlying the effects of neonatal sevoflurane on neuropsychiatric-like behavioral changes

Lin D, Liu J, Cottrell J, Kass I
SUNY Downstate, Brooklyn, NY, United states

Converging evidence from human and animal studies show that neonatal exposure to volatile anesthetics increases the risk of learning and memory deficits during adolescence. Perturbation of neurons during a critical developmental time window is associated with numerous neuropsychological disorders in addition to learning and memory deficits. Whether exposure to anesthetics during early brain development impose similar risks and the mechanisms underlying the deleterious effects of volatile anesthetics on the developing brain remain unclear. Previous studies from our lab have shown that the signaling pathway kinase mTOR is involved in sevoflurane (sevo) mediated downstream effects. We hypothesized that exposure to volatile anesthetics such as sevo during the early postnatal period would result in changes in the mTOR-related downstream signaling pathway, resulting in behavioral changes.
Male C57BL6 mice were exposed to 2% sevo for 2 hours on postnatal day 7(P7). Starting at peri-adolescence P27 and continued until adult (2-3 months), untreated and sevo treated mice underwent a battery of behavioral tests. Hippocampal tissue samples were taken after the completion of behavior tests and examined for changes in gene expression using western blot hybridization.
The hippocampus-dependent spatial learning and memory task, Active Place Avoidance, showed that sevo treated mice had significantly more entrances into the shock zone. Social-interaction tests showed that sevo treated mice had significantly decreased interest toward novel social targets compared to the non-sevo treated mice. We confirmed that changes in these behaviors were not due to impairment of olfaction. Additional behavioral tests showed no difference in repetitive behaviors. We then examined changes in the expression of two genes, phosphorylated-mTOR and PKMzeta, a gene that is critically associated with learning and memory and a downstream effector gene of mTOR. Although adult brains showed no change in the expression of these two genes, we are still in the process of analyzing postnatal brains immediately after treatment with sevo.
Our lab has confirmed that early life anesthetic exposure impairs cognitive function during peri-adolescent age. We initiated a battery of neuropsychiatric behavioral experiments and demonstrated changes in social interaction. These behaviors have been shown to be impaired in mouse models of neuropsychological disorders, such as Autism Spectrum Disorder. In order to understand the mechanisms underlying the observed changes in behavior, we are investigating changes in genes and microRNA expression from postnatal brains immediate after sevo exposure.


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