General anesthetics, a mixture of a hypnotic sedative that makes us sleep, an opioid analgesic to avoid pain, and a muscle relaxant to suppress muscle tone – for adults – have a more widespread effect on the brain than inducing sleep. suggests a new study carried out by scientists at the University of Queensland (Australia), a discovery that could lead to better drugs for use in surgery.
The team explains in 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 individual cells. Specifically, they studied the effect of the drug on synaptic release , a mechanism through which nerve cells or neurons communicate with each other.
“We know from previous research that general anesthetics, including propofol, act on the sleep systems in the brain, just like a sleeping pill,” says Bruno van Swinderen, a work leader.
However, in their experiment they examined the effects of the drug on rats and flies, discovering that propofol could also act quite differently. The drug “disrupts presynaptic mechanisms, likely affecting communication between neurons throughout the brain in a systematic way that differs from simply being asleep,” says van Swinderen.
Thus, propofol restricts the mobility of a protein called syntaxin 1A , necessary at neuronal synapses for neurons to communicate with each other.
Most of the signals are carried by chemical messengers called neurotransmitters. These are released by the presynaptic neuron and received in the postsynaptic cell.
The new finding is significant because, as the authors point out, “each neuron communicates with other neurons through syntaxin1A-mediated neurotransmission,” and the mechanism is the same in all species, from worms to humans.
Implications for people with Alzheimer’s
While propofol and other general anesthetics make us sleepy, it is their widespread disruption of synaptic connectivity or communication pathways throughout the brain that makes surgery possible.
“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 disease or Parkinson’s,” adds van Swinderen.
Obviously, more research is needed to determine whether or not general anesthetics produce long-term side effects in these vulnerable groups and, as van Swinderen explains, “it has never been understood why general anesthesia is sometimes problematic for patients. younger and older. This recently discovered mechanism may be one reason. “
Reference: Trapping of Syntaxin1a in Presynaptic Nanoclusters by a Clinically Relevant General Anesthetic. Adekunle T. Bademosi, James Steeves, Shanker Karunanithi, Oressia H. Zalucki, Rachel S. Gormal, Shu Liu, Elsa Lauwers, Patrik Verstreken, Victor Anggono, Frederic A. Meunier, Bruno van Swinderen. Cell Reports 2017. DOI: http://dx.doi.org/10.1016/j.celrep.2017.12.054
