Neurology: Long-term benzodiazepine use attacks synapses
LMU and DZNE scientists show in animal models that benzodiazepines lead to the loss of neural connections in the brain.
© E. Fessler, Jae Lab
DELE1 (green) is constantly imported into mitochondria (magenta) and degraded there. Errors in this process warn the cell nucleus (blue).
“While it was known that microglia play an important role in the elimination of synapses both during brain development and in neurodegenerative diseases. What was very surprising to us, however, was that drugs as well-studied as benzodiazepines affect this process.”
Yuan Shi and Mochen Cui
co-authors of the study
Especially in elderly people, long-term use of the widely used tranquilizers can lead to cognitive impairment. The study provides the first mechanistic explanation and may influence future treatment of people at risk for dementia, according to the authors. Benzodiazepines may lead to cognitive impairment
Benzodiazepines may lead to cognitive impairment
Benzodiazepines are effective and widely used medications to treat anxiety and sleep disorders. While short-term treatments are considered safe, their long-term use can lead to physical dependence and, especially in the elderly, cognitive impairment. The way in which benzodiazepines trigger these changes was previously unknown. Researchers led by Prof. Jochen Herms and Dr. Mario Dorostkar from the Center for Neuropathology and Prion Research at LMU and the German Center for Neurodegenerative Diseases have now been able to demonstrate in an animal model that the drug leads to the loss of nerve connections in the brain.
Synapses are degraded and recycled by activated microglia
Immune cells of the brain, so-called microglia, play a central role in this process. Benzodiazepines bind to a specific protein – the translocator protein (TSPO) – on the surface of cell organelles of the microglia. This binding activates the microglia, which then break down and recycle synapses, connections between neurons. Experiments by the scientists showed that synapse loss led to cognitive impairment in mice that had received a sleep-inducing dose of the benzodiazepine diazepam daily for several weeks.
“While it was known that microglia play an important role in the elimination of synapses both during brain development and in neurodegenerative diseases,” said Drs. Yuan Shi and Mochen Cui, co-authors of the study. “But what was very surprising to us was that drugs as well-studied as benzodiazepines affect this process.” After stopping diazepam, the effect lasted even longer, but was ultimately reversible.
New insights for treatment of sleep disorders and anxiety
According to the researchers, the study could have implications for the treatment of sleep disorders and anxiety in people at risk for dementia. “Drugs known to have no affinity for TSPO should be preferred when possible,” the authors said.
Dr. Mario Dorostkar
Zentrum für Neuropathologie
T: +49 89 2180 78065
Prof. Dr. Jochen Herms
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) und
Munich Cluster for Systems Neurology (SyNergy)
T: +49 89 4400 46427