Benzodiazepines are among the most commonly prescribed drugs for sleep and anxiety disorders. But if you take the medication over a longer period of time, your mental performance can suffer, even to the point of dementia. A team led by Yuan Shi from the Ludwig Maximilians University in Munich has now used complex experiments to discover how these serious side effects occur.
The experts limited their experiments to the active ingredient diazepam, better known as Valium. When they gave it to mice, the spinous processes on their nerve endings regressed. The synapses through which nerve cells communicate with one another are located on these “spines”. In addition, the laboratory animals degraded cognitively. Diazepam docks not only to the GABA receptor in the contact points of neurons, but also to the “translocator protein” (TSPO). If the brain researchers only activated this protein, the spinous processes also disappeared. Genetically modified mice without TSPO, on the other hand, did not lose any spines due to diazepam.
In further studies, Shi and her colleagues demonstrated that TSPO stimulates microglia, the brain’s immune cells. These interfere with the processes at the nerve endings and prevent new spinous processes from growing. When the scientists experimentally removed most of the microglia, even more spines formed in the diazepam and control groups. It was already known that microglia attack synapses. “But what really surprised us was that well-researched drugs like benzodiazepines affect this process,” says Yuan Shi.