General Anesthetics Impair Presynaptic Neurotransmitter Release

A team of researchers from University of Queensland have overturned previous understanding of what general anaesthetics do to the brain, finding the drugs do much more than induce sleep.

A new understanding of the complex ways in which general anaesthetics act on the brain could eventually lead to improved drugs for surgery. It remains unclear how general anaesthesia works, even though it is one of the most common medical procedures worldwide.

“We looked at the effects of propofol – one of the most common general anaesthetic drugs used during surgery – on synaptic release,”

said Associate Professor Bruno van Swinderen, of the UQ Queensland Brain Institute.

Synaptic Release

Synaptic release is the mechanism by which neurons communicate with each other.

“We know from previous research that general anaesthetics including propofol act on sleep systems in the brain, much like a sleeping pill. But our study found that propofol also disrupts presynaptic mechanisms, probably affecting communication between neurons across the entire brain in a systematic way that differs from just being asleep. In this way it is very different than a sleeping pill,”

Associate Professor van Swinderen said.

PhD student Adekunle Bademosi added the discovery shed new light on how general anaesthetics worked on the brain.

“We found that propofol restricts the movement of a key protein (syntaxin1A) required at the synapses of all neurons. This restriction leads to decreased communication between neurons in the brain.”

van Swinderen said the finding contributed to understanding how general anaesthetics worked, and could explain why people experienced grogginess and disorientation after coming out of surgery:

“We think that widespread disruption to synaptic connectivity – the brain’s communication pathways – is what makes surgery possible, although effective anaesthetics such as propofol do put you to sleep first. 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.

It has never been understood why general anaesthesia is sometimes problematic for the very young and the old. This newly discovered mechanism may be a reason.”

More research is needed to determine if general anaesthetics had any lasting effects in these vulnerable groups of people.

Bademosi, Adekunle T. et al.
Trapping of Syntaxin1a in Presynaptic Nanoclusters by a Clinically Relevant General Anesthetic
Cell Reports, Volume 22 , Issue 2 , 427 – 440

Image: thousands of tracked syntaxin1A molecules in a neuron exposed to propofol. Credit: Associate Professor Bruno van Swinderen