Developmental Stage-dependent Persistent Impact of Propofol Anesthesia on Dendritic Spines in the Rat Medial Prefrontal Cortex

Background: Recent observations demonstrate that anesthetics rapidly impair synaptogenesis during neuronal circuitry development. Whether these effects are lasting and depend on the developmental stage at which these drugs are administered remains, however, to be explored. Methods: Wistar rats received propofol anesthesia at defined developmental stages during early postnatal life. The acute and long-term effects of these treatments on neuronal cytoarchitecture were evaluated by Neurolucida and confocal microscopy analysis after iontophoretic injections of Lucifer Yellow into layer 5 pyramidal neurons in the medial prefrontal cortex. Quantitative electron microscopy was applied to investigate synapse density. Results: Layer 5 pyramidal neurons of the medial prefrontal cortex displayed intense dendritic growth and spinogenesis during the first postnatal month. Exposure of rat pups to propofol at postnatal days 5 and 10 significantly decreased dendritic spine density, whereas this drug induced a significant increase in spine density when administered at postnatal days 15, 20, or 30. Quantitative electron microscopy revealed that the propofol-induced increase in spine density was accompanied by a significant increase in the number of synapses. Importantly, the propofol-induced modifications in dendritic spine densities persisted up to postnatal day 90. Conclusion: These new results demonstrate that propofol anesthesia can rapidly induce significant changes in dendritic spine density and that these effects are developmental stage-dependent, persist into adulthood, and are accompanied by alterations in synapse number. These data suggest that anesthesia in the early postnatal period might permanently impair circuit assembly in the developing brain.