General anesthetics have a more widespread effect on the brain than inducing sleep, suggests a new study that could lead to improved drugs for use in surgery. Researchers now suggest that general anesthetics do much more than simply induce sleep. The team, from the University of Queensland in Australia, write in the journal Cell Reports that their "findings may provide a more complete understanding of general anesthesia." Using a technique known as single-molecule imaging microscopy, the scientists were able to explore the effect of propofol, a common general anesthetic, on single cells. Specifically, they studied the effect of the drug on synaptic release, which is a mechanism through which nerve cells, or neurons, communicate with one another. "We know from previous research," says senior study author Bruno van Swinderen, an associate professor in the Queensland Brain Institute, "that general anesthetics including propofol act on sleep systems in the brain, much like a sleeping pill." Disruption to synaptic mechanisms But, in the new study — in which they examined the drug's effects in rats and flies — the scientists found that propofol can also act in another, quite different, way. As Prof. van Swinderen explains, the team found that the drug "disrupts presynaptic mechanisms, probably affecting communication between neurons across the entire brain in a systematic way that differs from just being asleep." He and his team found that propofol restricts the mobility of a protein called syntaxin1A, which is needed at neuron synapses in order for neurons to communicate with each other. Synapses are junctions at which neurons transmit signals to other neurons as well as other types of cell, such as gland and muscle cells. Most signals are carried by chemical messengers called neurotransmitters. These are released by the presynaptic neuron and received at the postsynaptic cell. The new finding is significant because, as Prof. van Swinderen and his colleagues note in their study paper, "Every neuron communicates with other neurons by way of syntaxin1A-mediated neurotransmission," and the mechanism is the same across species, ranging from "worms to humans." Implications for people with Alzheimer's Prof. van Swinderen says that the team's recent discovery might explain some of the side effects of general anesthesia, such as why we feel groggy and disoriented after surgery. While propofol and other general anesthetics do put us to sleep, it is their "widespread disruption to synaptic connectivity" — or the communication pathways throughout the brain — that make surgery possible, he suggests. "The discovery has implications for people whose brain connectivity is vulnerable, for example in children whose brains are still developing or for people with Alzheimer's or Parkinson's disease," Prof. van Swinderen adds. He says that more work is needed to determine whether or not general anesthetics produce long-term side effects in these vulnerable groups. "It has never been understood why general anesthesia is sometimes problematic for the very young and the old. This newly discovered mechanism may be a reason." Prof. Bruno van Swinderen Source
