Clinically relevant concentrations of propofol but not midazolam alter in vitro dendritic development of isolated γ-aminobutyric acid-positive interneurons

Laszlo Vutskits, Eduardo Gascon, E. Tassonyi, J. Kiss

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Abstract

Background: Recent laboratory studies showed that exposure to supraclinical concentrations of propofol can induce cell death of immature neurons. However, no data are available regarding the effects of clinically relevant concentrations of this agent on neuronal development. The authors addressed this issue by evaluating the effect of propofol on dendritic growth and arbor expansion of developing γ-aminobutyric acid-positive (GABAergic) interneurons. Methods: Immature neuroblasts were isolated from the newborn rat subventricular zone and differentiated into GABAergic interneurons in culture. In addition to cell death, the effects of increasing concentrations and durations of propofol exposure on neuronal dendritic development were evaluated using the following morphologic parameters: total dendritic length, primary dendrites, branching point, and Scholl analysis. Results: The authors demonstrate that propofol induced cell death of GABAergic neurons at concentrations of 50 μg/ml or greater. As little as 1 μg/ml propofol significantly altered several aspects of dendritic development, and as little as 4 h of exposure to this agent resulted in a persistent decrease in dendritic growth. In contrast, application of midazolam did not affect neuronal development. Conclusion: Short-term exposure of immature developing GABAergic neurons to clinically relevant concentrations of propofol can induce long-term changes in dendritic arbor development. These results suggest that propofol anesthesia during central nervous system development could interfere with the molecular mechanisms driving the differentiation of GABAergic neurons and thus could potentially lead to impairment of neural networks.

Original languageEnglish
Pages (from-to)970-976
Number of pages7
JournalAnesthesiology
Volume102
Issue number5
DOIs
Publication statusPublished - May 2005

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Aminobutyrates
Midazolam
Interneurons
Propofol
GABAergic Neurons
Cell Death
Lateral Ventricles
Growth
Dendrites
In Vitro Techniques
Anesthesia
Central Nervous System
Neurons

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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Clinically relevant concentrations of propofol but not midazolam alter in vitro dendritic development of isolated γ-aminobutyric acid-positive interneurons. / Vutskits, Laszlo; Gascon, Eduardo; Tassonyi, E.; Kiss, J.

In: Anesthesiology, Vol. 102, No. 5, 05.2005, p. 970-976.

Research output: Contribution to journalArticle

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