CRISPR Technology Targets Mood-Boosting Receptors in Brain


Source: Washington University School of Medicine in St. Louis

Summary: Using CRISPR technology, the scientists have been able to target an altogether different type of receptor called delta-type GABA receptors. They think that natural mood-boosting substances in the brain can target these receptors.


An estimated 13% of Americans take antidepressant drugs for depression, anxiety, chronic pain or sleep problems. For the 14 million Americans who have clinical depression, roughly one third don’t find relief with antidepressants. The most commonly prescribed antidepressant drugs such as Prozac, Paxil and Zoloft were approved by the FDA more than 30 years ago, and there’s been a dearth of new antidepressants since then. A completely new approach is warranted. Now researchers at Washington University School of Medicine in St. Louis and Sage Therapeutics in Boston are trying a different approach to alleviate depression. Most antidepressant drugs target serotonin receptors, aiming to boost serotonin, a chemical thought to regulate mood and social behavior. Using CRISPR technology, the scientists have been able to target an altogether different type of receptor called delta-type GABA receptors. They think that natural mood-boosting substances in the brain can target these receptors. The study findings were published in The Journal of Neuroscience.

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Pictured is a neuron, colored with dye, from the brain’s hippocampus. Credit: Mennerick lab

A new approach involves targeting GABA receptors with substances called neurosteroids, chemicals that occur naturally in the brain and are involved in emotional and motivational brain networks. In the new research, the research team focused on GABA receptors located on neurons in the brain’s hippocampus, a part of the brain involved in learning and memory. Using CRISPR, they mutated the delta-type GABA receptors to isolate and test their role in brain functioning. The drugs affect GABA receptors, but they also seem to have anti-inflammatory properties. The team explained that if further studies confirm that activating delta-type receptors has antidepressant effects, a next step would be to develop and test more compounds that activate those receptors. They said the mutant mice give them the tool they need to develop more potent drugs that also are more selective, with fewer side effects.

First author Min-Yu Sun, PhD, a postdoctoral researcher said, “It’s very difficult to differentiate among different types of GABA receptors because they share so many common properties” and further added, “Previously, scientists really had no way to isolate the subtypes, but we can do that with CRISPR/Cas9 gene editing technology to learn how particular drugs affect individual receptor subtypes.”


More Information: Min-Yu Sun et al, “Chemogenetic isolation reveals synaptic contribution of δ GABAA receptors in mouse dentate granule neurons”, The Journal of Neuroscience (2018). DOI: 10.1523/JNEUROSCI.0799-18.2018


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