An acid-sensitive protein in the brain may represent a new target for the treatment of depression, according to animal research in the April 29 issue of The Journal of Neuroscience.
The study shows that disrupting acid-sensitive ion channel-1a (ASIC1a) produces antidepressant-like effects in mice. The findings may one day benefit people who do not respond to traditional antidepressants or who cannot tolerate their side effects.
"Depression is one of the most devastating and difficult-to-treat disorders known to man," said John F. Cryan, PhD, at University College Cork in Ireland, who was not affiliated with the study. "Despite much research, all antidepressant medications that are currently prescribed work in much the same way and are of limited efficacy in more than a third of all patients. The development of antidepressants that act on other molecular targets in the brain would be a major breakthrough," Cryan said.
Although animal models cannot reproduce all of the symptoms of human depression, several behavioral tests in rodents are sensitive to antidepressant treatment, suggesting that they address important aspects of the disease. For example, chronically stressed mice lose their normal preference for sugary drinks, and mice repeatedly placed in a pool of water tend to give up and float rather than swim in the hopes of escaping.
These mouse behaviors are thought to reflect loss of interest in pleasurable activities and hopelessness or despair. But traditional antidepressants are able to restore the mouse preference for sweet treats and reduce the amount of time that they float rather than swim.
The researchers, led by Matthew Coryell, PhD and senior researcher John Wemmie, MD, PhD, at the University of Iowa, found that mice lacking the ASIC1a gene and normal mice treated with drugs that inhibit ASIC1a showed reduced depression-like behaviors. These mice showed increased sweet taste preference and reduced immobility, consistent with antidepressant treatment.
Mice lacking the ASIC1a gene also failed to show a known biomarker for depression. Chronic stress normally decreases the amount of the BDNF gene in the brain, but mice lacking ASIC1a failed to show this change.
The researchers found that ASIC1a-based treatment works through a different biological pathway than traditional antidepressants, suggesting that it may benefit people who do not respond to traditional therapies.
ASIC1a is located in brain structures associated with mood, including the amygdala, which is critical for so-called negative emotions such as anger, anxiety, and fear. The researchers previously showed reduced amygdala activity in animals that lacked the ASIC1a gene. In the current study, they reversed the antidepressant effect of ASIC1a gene deletion by turning the ASIC1a gene back on only in the amygdala. These findings support the idea that depression could be caused, at least in part, by hyperactivity of the amygdala.
"ASIC1a inhibitors may combat depression by reducing amygdala activity. Because of the importance of the amygdala in negative emotions and fear, we speculate that ASIC1a inhibition increases the brain's resistance to the negative effects of stress, perhaps reducing the likelihood of developing depression," said study author Wemmie.
The research was supported by the National Institute of Mental Health, the National Alliance for Research on Schizophrenia and Depression, and the Department of Veteran Affairs.
The Journal of Neuroscience is published by the Society for Neuroscience, an organization of more than 38,000 basic scientists and clinicians who study the brain and nervous system. Wemmie can be reached at firstname.lastname@example.org.
Todd Bentsen | EurekAlert!
Further reports about: > ASIC1a > ASIC1a-based treatment > Amygdala > Chronic Stress > Cryan > Depression > acid-sensitive protein > amygdala activity > antidepressant effects > antidepressant treatment > brain structure > difficult-to-treat disorders > hopelessness > hyperactivity > molecular targets > negative emotions > pleasurable activities > schizophrenia > symptoms of human depression > traditional therapies
Advanced analysis of brain structure shape may track progression to Alzheimer's disease
26.10.2016 | Massachusetts General Hospital
Indian roadside refuse fires produce toxic rainbow
26.10.2016 | Duke University
Physicists from the University of Würzburg have designed a light source that emits photon pairs. Two-photon sources are particularly well suited for tap-proof data encryption. The experiment's key ingredients: a semiconductor crystal and some sticky tape.
So-called monolayers are at the heart of the research activities. These "super materials" (as the prestigious science magazine "Nature" puts it) have been...
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
28.10.2016 | Power and Electrical Engineering
28.10.2016 | Physics and Astronomy
28.10.2016 | Life Sciences