Long-term fate-mapping to assess the impact of postnatal isoflurane exposure on granule cell pre- and post-synaptic terminal structure
Grade Level at Time of Presentation
Junior
Major
undeclared
Minor
undeclared
Institution
Morehead State University
KY House District #
4
KY Senate District #
11
Faculty Advisor/ Mentor
Andreas Loepke, MD, PhD, FAAP; Steve Danzer, PhD
Department
Dept. of Biology
Abstract
Use of general anesthetics in children is necessary for the treatment of conditions that require surgical intervention. Studies in developing animals, however, demonstrate that clinically relevant anesthesia-treatments increase neuronal death and alter brain structure. Notably, neuron production during development follows a complex temporal sequence, such that at any given time the developing brain can contain fully mature neurons, immature neurons, and active neural progenitors. Recent work demonstrates that anesthetics selectively disrupt neurons of distinct ages. In the hippocampal dentate gyrus, two-week-old immature granule cells were found to be selectively vulnerable to anesthesia-induced cell death. Only about 10% of these cells succumbed to acute exposure to anesthesia, raising the possibility that the surviving cells might be “injured”, and integrate abnormally into the brain. To address this possibility, we used a transgenic mouse model fate-mapping approach to identify and label immature granule cells. Cells were exposed to isoflurane for 6 hours when they were two weeks old, and then their morphology examined two months later. Exposed granule cells exhibited normal positioning, spine density, and presynaptic structure, suggesting that anesthesia does not impair the integration of this specific age-cohort of cells. Nonetheless, while two-week-old cells were found to recover from anesthesia exposure, the results should not be extrapolated to other age-cohorts, which may respond differently.
Long-term fate-mapping to assess the impact of postnatal isoflurane exposure on granule cell pre- and post-synaptic terminal structure
Use of general anesthetics in children is necessary for the treatment of conditions that require surgical intervention. Studies in developing animals, however, demonstrate that clinically relevant anesthesia-treatments increase neuronal death and alter brain structure. Notably, neuron production during development follows a complex temporal sequence, such that at any given time the developing brain can contain fully mature neurons, immature neurons, and active neural progenitors. Recent work demonstrates that anesthetics selectively disrupt neurons of distinct ages. In the hippocampal dentate gyrus, two-week-old immature granule cells were found to be selectively vulnerable to anesthesia-induced cell death. Only about 10% of these cells succumbed to acute exposure to anesthesia, raising the possibility that the surviving cells might be “injured”, and integrate abnormally into the brain. To address this possibility, we used a transgenic mouse model fate-mapping approach to identify and label immature granule cells. Cells were exposed to isoflurane for 6 hours when they were two weeks old, and then their morphology examined two months later. Exposed granule cells exhibited normal positioning, spine density, and presynaptic structure, suggesting that anesthesia does not impair the integration of this specific age-cohort of cells. Nonetheless, while two-week-old cells were found to recover from anesthesia exposure, the results should not be extrapolated to other age-cohorts, which may respond differently.