Now MIT researchers have found novel C. elegans neurochemical receptors, the discovery of which could lead to new therapeutic targets for psychiatric disorders if similar receptors are found in humans.
Dopamine and serotonin are members of a class of neurochemicals called biogenic amines, which function in neuronal circuitry throughout the brain. Many drugs used to treat psychiatric disorders, including depression and schizophrenia, target these signaling systems, as do cocaine and other drugs of abuse. Scientists have long known of a class of biogenic-amine receptors that are G protein-coupled receptors (GPCRs) and that, when activated, trigger a slow but long-lasting cascade of intracellular events that modulate nervous system activity.
A study in the July 3 issue of Science has found that in C. elegans these chemicals also act on receptors of a fundamentally different type. These receptors are chloride channels that open and close quickly in response to the binding of a neurochemical messenger. By allowing the passage of negatively charged chloride ions across the cell membrane, chloride channels can rapidly inactivate nerve cells.
"These results underscore the importance of determining whether, as in the C. elegans nervous system, a diversity of biogenic amine-gated chloride channels function in the human brain,” said H. Robert Horvitz of the McGovern Institute for Brain Research at MIT and senior author of the study. “If so, such channels might define novel therapeutic targets for neuropsychiatric disorders, such as depression and schizophrenia."
In 2000, Horvitz’s group discovered that serotonin activates a chloride channel they called MOD-1, which inhibits neuronal activity in C. elegans.
In the current study, Niels Ringstad and Namiko Abe, a postdoctoral researcher and an undergraduate in Horvitz’s laboratory, respectively, looked for other ion channels that could be receptors for biogenic amines. Using both in vitro and in vivo methods, they surveyed the functions of 26 ion channels similar to MOD-1 and found three additional ion channels with an affinity for biogenic amines: dopamine activates one, serotonin another, and tyramine (the role of which in the human brain is unknown) a third. All three were chloride channels, like MOD-1.
“We now have four members of a family of chloride channels that can act as receptors for biogenic amines in the worm,” Ringstad said. “That these neurochemicals activate both GPCRs and ion channels means that they can have very complex actions in the nervous system, both as slow-acting neuromodulators and as fast-acting inhibitory neurotransmitters.”
It is unknown as yet whether an equivalent to this new class of worm receptor exists in the human brain, but Horvitz points out that worms have proved remarkably informative for providing insights into human biology. In 2002, Horvitz shared the Nobel Prize in Physiology or Medicine for the discovery based on studies of C. elegans of the mechanism of programmed cell death, a central feature of some neurodegenerative diseases and many other disorders in humans.
“Historically, studies of C. elegans have delineated mechanisms of neurotransmission that subsequently proved to be conserved in humans,” says Horvitz, the David H. Koch Professor of Biology at MIT and a Howard Hughes Medical Institute Investigator. “The next step is to look for chloride channels controlled by biogenic amines in mammalian neurons.”
This study was supported by the NIH, the Howard Hughes Medical Institute, the Life Sciences Research Foundation, and The Medical Foundation.
Broadcast quality video is available upon request.
Elizabeth Thomson | Newswise Science News
Further reports about: > Brain Research > C. elegans > C. elegans nervous system > Caenorhabditis elegans > GPCRs > MOD-1 > Medical Wellness > Neurochemicals > Science TV > biogenic-amine receptors > cell membrane > chloride channels > human brain > human brain function > nervous system > neurochemical receptors > neurodegenerative disease > protein-coupled receptors > psychiatric disorder
Molecular Force Sensors
20.09.2017 | Max-Planck-Institut für Biochemie
Foster tadpoles trigger parental instinct in poison frogs
20.09.2017 | Veterinärmedizinische Universität Wien
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...
Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
20.09.2017 | Life Sciences
20.09.2017 | Power and Electrical Engineering
20.09.2017 | Physics and Astronomy