While benzodiazepine drugs were previously thought to work on their own to calm anxiety or stave off insomnia, researchers have discovered that a “sticky gene” is actually needed in the process. This conclusion may change the view we have of these drugs and the neural circuits they affect.
The French are the second biggest consumers of benzodiazepines in Europe, behind the Spaniards. These drugs are used to treat anxiety or insomnia. However, it is also in France that the decrease in consumption is the strongest. Between 2012 and 2015, it was 10%, compared to 5.1% in Europe. In the United States, on the other hand, the trend is one of constant increase. More than one in eight Americans used benzodiazepines during 2018. Between 1999 and 2017, the number of people who died from an overdose of Valium® increased tenfold.
For years, the scientific community believed that these sedatives worked on their own to calm anxiety. But researchers at the National Institutes of Health have found in a study on mice that they actually need a “sticky gene” to be effective. The results of this work are published in the journal Science.
Shisa7 gene reduces nervous system excitability
This gene was called Shisa7, in reference to a mythological figure. “We found that Shisa7 plays an essential role in the regulation of inhibitory neural circuits and in the sedative effects that benzodiazepines have on these circuits,” says Wei Lu, lead author of the study. These drugs, by binding to a specific receptor, facilitate the action of a neurotransmitter, GABA (gamma amino butyric acid). This neurotransmitter decreases the excitability of the central nervous system. Prior to this study, scientists believed that benzodiazepines acted alone to stimulate GABA receptor responses. However, according to the findings of Dr. Lu, this response is due to the fact that the Shisa7 gene is stuck to these receptors.
A “sticky gene”, which increases the effects of the drug
To conduct this study, Dr. Lu and his team worked on mice, using advanced microscopic techniques to identify the presence of the Shisa7 gene. By eliminating subsequently this gene, the researchers found a decrease in the number of GABA neurotransmitters. Moreover, it turned out that the presence of the Shisa7 gene increased the activity of GABA neurotransmitters, and even doubled the magnitude of the responses in the presence of Valium®. This discovery shows that the “sticky gene” Shisa7 makes the receptor more sensitive to benzodiazepines. “These results suggest that Shisa7 directly determines synapse responses under various conditions, including the presence of benzodiazepines,” said Dr. McBain, one of the study’s authors.
“Our results shed light on the potential clinical importance of helper proteins such as Shisa7. Many neurological drugs we use today are designed to control synaptic receptor activity. For the first time, we are showing that researchers can Also consider proteins like Shisa7 in the development of new treatments, which target GABA neurotransmitters,” concludes Dr. Lu.
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