May 29, 2020 05:14 PM
Anesthesia's effect on consciousness solved, settling century-old scientific debate
https://www.eurekalert.org/pub_releases/...052920.php
INTRO: Surgery would be inconceivable without general anesthesia, so it may come as a surprise that despite its 175-year history of medical use, doctors and scientists have been unable to explain how anesthetics temporarily render patients unconscious.
A new study from Scripps Research published Thursday evening in the Proceedings of the National Academies of Sciences (PNAS) solves this longstanding medical mystery. Using modern nanoscale microscopic techniques, plus clever experiments in living cells and fruit flies, the scientists show how clusters of lipids in the cell membrane serve as a missing go-between in a two-part mechanism. Temporary exposure to anesthesia causes the lipid clusters to move from an ordered state, to a disordered one, and then back again, leading to a multitude of subsequent effects that ultimately cause changes in consciousness.
The discovery by chemist Richard Lerner, MD, and molecular biologist Scott Hansen, PhD, settles a century-old scientific debate, one that still simmers today: Do anesthetics act directly on cell-membrane gates called ion channels, or do they somehow act on the membrane to signal cell changes in a new and unexpected way? It has taken nearly five years of experiments, calls, debates and challenges to arrive at the conclusion that it's a two-step process that begins in the membrane, the duo say. The anesthetics perturb ordered lipid clusters within the cell membrane known as "lipid rafts" to initiate the signal.
"We think there is little doubt that this novel pathway is being used for other brain functions beyond consciousness, enabling us to now chip away at additional mysteries of the brain," Lerner says... (MORE)
New gut-brain link: how gut mucus could help treat brain disorders
https://www.rmit.edu.au/news/media-relea...rain-mucus
RELEASE: Mucus is the first line of defence against bad bacteria in our gut. But could it also be part of our defence against diseases of the brain? Bacterial imbalance in the gut is linked with Alzheimer’s disease, autism and other brain disorders, yet the exact causes are unclear. Now a new research review of 113 neurological, gut and microbiology studies led by RMIT University suggests a common thread – changes in gut mucus.
Senior author Associate Professor Elisa Hill-Yardin said these changes could be contributing to bacterial imbalance and exacerbating the core symptoms of neurological diseases. “Mucus is a critical protective layer that helps balance good and bad bacteria in your gut but you need just the right amount - not too little and not too much,” Hill-Yardin said.
“Researchers have previously shown that changes to intestinal mucus affect the balance of bacteria in the gut but until now, no-one has made the connection between gut mucus and the brain. Our review reveals that people with autism, Parkinson’s disease, Alzheimer’s and Multiple Sclerosis have different types of bacteria in their gut mucus compared with healthy people, and different amounts of good and bad bacteria. It’s a new gut-brain connection that opens up fresh avenues for scientists to explore, as we search for ways to better treat disorders of the brain by targeting our ‘second brain’ – the gut.”
Gut mucus is different depending on where it’s found in the gastrointestinal tract - in the small intestine it’s more porous so nutrients from food can be easily absorbed, while in the colon, the mucus is thick and should be impenetrable to bacteria. The mucus is full of peptides that kill bacteria, especially in the small intestine, but it can also act as an energy source, feeding some of the bacteria that live inside it.
Scientists are learning that brain disorders can affect neurons in the gut. For example, RMIT researchers have shown that neurons in both the brain and the gut nervous systems are affected in autism. The new review suggests that reduced gut mucus protection may make patients with neurological diseases more susceptible to gastrointestinal problems.
Hill-Yardin said severe gut dysfunction could exacerbate the symptoms of brain disorders, significantly affecting quality of life for patients and their families. “If we can understand the role that gut mucus plays in brain disease, we can try to develop treatments that harness this precise part of the gut-brain axis,” she said. “Our work shows that microbial engineering, and tweaking the gut mucus to boost good bacteria, have potential as therapeutic options for neurological disorders.”
Hill-Yardin, an ARC Future Fellow and Vice-Chancellor’s Senior Research Fellow at RMIT, led the review with collaborators from University of Melbourne and La Trobe University.
https://www.eurekalert.org/pub_releases/...052920.php
INTRO: Surgery would be inconceivable without general anesthesia, so it may come as a surprise that despite its 175-year history of medical use, doctors and scientists have been unable to explain how anesthetics temporarily render patients unconscious.
A new study from Scripps Research published Thursday evening in the Proceedings of the National Academies of Sciences (PNAS) solves this longstanding medical mystery. Using modern nanoscale microscopic techniques, plus clever experiments in living cells and fruit flies, the scientists show how clusters of lipids in the cell membrane serve as a missing go-between in a two-part mechanism. Temporary exposure to anesthesia causes the lipid clusters to move from an ordered state, to a disordered one, and then back again, leading to a multitude of subsequent effects that ultimately cause changes in consciousness.
The discovery by chemist Richard Lerner, MD, and molecular biologist Scott Hansen, PhD, settles a century-old scientific debate, one that still simmers today: Do anesthetics act directly on cell-membrane gates called ion channels, or do they somehow act on the membrane to signal cell changes in a new and unexpected way? It has taken nearly five years of experiments, calls, debates and challenges to arrive at the conclusion that it's a two-step process that begins in the membrane, the duo say. The anesthetics perturb ordered lipid clusters within the cell membrane known as "lipid rafts" to initiate the signal.
"We think there is little doubt that this novel pathway is being used for other brain functions beyond consciousness, enabling us to now chip away at additional mysteries of the brain," Lerner says... (MORE)
New gut-brain link: how gut mucus could help treat brain disorders
https://www.rmit.edu.au/news/media-relea...rain-mucus
RELEASE: Mucus is the first line of defence against bad bacteria in our gut. But could it also be part of our defence against diseases of the brain? Bacterial imbalance in the gut is linked with Alzheimer’s disease, autism and other brain disorders, yet the exact causes are unclear. Now a new research review of 113 neurological, gut and microbiology studies led by RMIT University suggests a common thread – changes in gut mucus.
Senior author Associate Professor Elisa Hill-Yardin said these changes could be contributing to bacterial imbalance and exacerbating the core symptoms of neurological diseases. “Mucus is a critical protective layer that helps balance good and bad bacteria in your gut but you need just the right amount - not too little and not too much,” Hill-Yardin said.
“Researchers have previously shown that changes to intestinal mucus affect the balance of bacteria in the gut but until now, no-one has made the connection between gut mucus and the brain. Our review reveals that people with autism, Parkinson’s disease, Alzheimer’s and Multiple Sclerosis have different types of bacteria in their gut mucus compared with healthy people, and different amounts of good and bad bacteria. It’s a new gut-brain connection that opens up fresh avenues for scientists to explore, as we search for ways to better treat disorders of the brain by targeting our ‘second brain’ – the gut.”
Gut mucus is different depending on where it’s found in the gastrointestinal tract - in the small intestine it’s more porous so nutrients from food can be easily absorbed, while in the colon, the mucus is thick and should be impenetrable to bacteria. The mucus is full of peptides that kill bacteria, especially in the small intestine, but it can also act as an energy source, feeding some of the bacteria that live inside it.
Scientists are learning that brain disorders can affect neurons in the gut. For example, RMIT researchers have shown that neurons in both the brain and the gut nervous systems are affected in autism. The new review suggests that reduced gut mucus protection may make patients with neurological diseases more susceptible to gastrointestinal problems.
Hill-Yardin said severe gut dysfunction could exacerbate the symptoms of brain disorders, significantly affecting quality of life for patients and their families. “If we can understand the role that gut mucus plays in brain disease, we can try to develop treatments that harness this precise part of the gut-brain axis,” she said. “Our work shows that microbial engineering, and tweaking the gut mucus to boost good bacteria, have potential as therapeutic options for neurological disorders.”
Hill-Yardin, an ARC Future Fellow and Vice-Chancellor’s Senior Research Fellow at RMIT, led the review with collaborators from University of Melbourne and La Trobe University.
