Editors' ChoiceNeuroscience

Can Anesthesia Make You Spineless?

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Science Translational Medicine  03 Aug 2011:
Vol. 3, Issue 94, pp. 94ec122
DOI: 10.1126/scitranslmed.3002964

Propofol is an opaque intravenous anesthetic that is often referred to as “milk of amnesia.” Although drugs such as propofol have revolutionized modern medicine by suppressing consciousness and memory formation during surgery, there is currently debate about their neurotoxic potential, especially in the very young and the very old. Briner et al. now show that propofol can affect the formation of dendritic spines in the medial prefrontal cortex of neonatal rats, raising further concern about its toxicity.

Dendrites are projections from neuronal cell bodies that receive incoming electrochemical information from other neurons, which occurs at small protrusions called spines. Dendritic spines are key sites for processing neural information and regulating synaptic strength, so their proper development is crucial. Briner and colleagues show that propofol has effects on dendritic spines that depend on the developmental stage of the animal. Using both light and electron microscopy, they imaged dendritic spines on pyramidal neurons in layer 5 of the prefrontal cortex. At postnatal days 5 and 10, exposure to propofol reduced the density of dendritic spines—a phenomenon that appeared to be dose-dependent. In contrast, exposure to propofol 15 or 20 days after birth led to a relative increase in spine density compared with that of the control, which was correlated with increased synaptic density. Both increases and decreases in spine density persisted when the rats were assessed at about 3 months of age.

The findings of Briner et al. suggest that exposure to propofol during postnatal development can result in altered neural circuitry. The stage-dependence of these results may relate to the neurotransmitter γ-amino butyric acid (GABA), which is potentiated by propofol. GABA acts as an excitatory transmitter in early development but, as the animal ages, shifts to be an inhibitory transmitter; this switch could potentially account for the opposing effects of propofol on spines at early and later ages. These propofol-induced alterations of dendritic spine formation and synaptic organization suggest that further studies in primates are necessary to investigate the cognitive implications of anesthetic effects in infants.

A. Briner et al., Developmental stage-dependent persistent impact of propofol anesthesia on dendritic spines in the rat medial prefrontal cortex. Anesthesiology 115, 282–293 (2011). [Abstract]

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