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Published on: December 3, 2021
Developmental Stage-dependent persistent impact of propofol anesthesia on dendritic spines in the rat medial
Adrian Briner1, Irina Nikonenko, Mathias De Roo
1Department of Anesthesiology, Pharmacology and Intensive Care, University Hospital of Geneva, Geneva, Switzerland.
Insights
Anesthesia with propofol during early development can alter brain circuitry, with effects on dendritic spine density persisting into adulthood. These changes depend on the specific developmental stage when the anesthesia is administered.
Area of Science:
- Neuroscience
- Developmental Biology
- Anesthesiology
Background:
- Anesthetics are known to rapidly impair synaptogenesis during neuronal development.
- The long-term consequences and developmental stage-dependency of these anesthetic effects remain largely unexplored.
Purpose of the Study:
- To investigate the acute and long-term effects of propofol anesthesia on neuronal cytoarchitecture.
- To determine if these effects are dependent on the developmental stage during early postnatal life.
Main Methods:
- Wistar rats were exposed to propofol anesthesia at specific postnatal developmental stages.
- Neuronal cytoarchitecture was analyzed using Neurolucida and confocal microscopy.
- Synapse density was quantified using electron microscopy.
Main Results:
- Propofol exposure at postnatal days 5 and 10 decreased dendritic spine density.
- Exposure at postnatal days 15, 20, and 30 increased dendritic spine density and synapse number.
- These propofol-induced modifications in spine density persisted until postnatal day 90.
Conclusions:
- Propofol anesthesia induces significant, developmental stage-dependent changes in dendritic spine density.
- These alterations in synapse number and spine density persist into adulthood.
- Early postnatal anesthesia may permanently impact brain circuit assembly.
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.
