Antidepressants are the most commonly used psychotropic drugs. However, they often improve the symptoms only after weeks or months, have strong side effects and do not work at all in many patients. Now, scientists at the University Hospital of Freiburg are introducing a new therapeutic approach in a mouse model that could largely solve this problem: They have linked the therapeutically active signaling protein Homer1a to a trafficking molecule that also allows the HI virus to enter cells. Thus, the active ingredient enters the nerve cell and can directly intervene in the signaling pathways of the cell.
"The active ingredient develops its anti-depressant activity without stopping and is thus significantly faster and stronger than classic antidepressants," says study leader Dr. Med. Tsvetan Serchov, Head of Research Group at the Department of Stereotactic and Functional Neurosurgery, Department of Neurosurgery, University Hospital of Freiburg. The study was published on August 13, 2019 in the reputable journal Neuron.
The 1980s approach to therapy could take on new meaning
Researchers have used a procedure known since the late 1980s but hardly used for therapeutic purposes. They have linked the tiny HI virus protein to important proteins for the treatment of Homer1a depression. HIV protein can easily penetrate the cell membrane due to its physicochemical properties. It transfers the therapeutically effective Homer protein through the blood-brain barrier and into the cell.
After the scientists injected the double molecule into the blood of the mice, it took only about an hour for the antidepressant to start acting. Researchers from Freiburg have identified Homer1a protein in recent years as an important cellular mediator in the treatment of depression. "In previous studies, we were able to show that not only drugs, but even the antidepressant effect of sleep deprivation lead to the activation of Homer proteins," Serchov says.
In a current study, developed in close collaboration with doctors and scientists at the Department of Psychiatry and Psychotherapy at the University Hospital of Freiburg, researchers also deciphered how Homer proteins develop their antidepressant activity. They activate surface proteins, called AMPA receptors, in which the cell responds more strongly to stimuli. This makes it easy to adapt and learn. If the Homer and AMPA proteins form less strongly, as in the brains of people who have severe depression, those affected will find these processes more difficult.
Use as a possible nasal spray
"The therapeutic approach has been very successful in the laboratory and animal models. More studies are now underway on possible side effects, drug metabolism and specific psychiatric use," Serchov says. "In the long run, imagine the drug would also be used as a nasal spray. It would come directly to the right brain region, the prefrontal cortex."
The Serchov research group is funded by the Deutsche Forschungsgemeinschaft and the Freiburg School of Medicine Albert-Ludwigs-Universität.
Dr. Tsvetan Serchov
Head of Research Group
Department of Stereotactic and Functional Neurosurgery
Department of Neurosurgery
Phone: 0761 270 50460
Original title: Enhanced mGlu5 signaling in excitatory neurons stimulates rapid antidepressant effects through activation of AMPA receptors
Doi: 10.1016 / j.neuron.2019.07.011
Studio Link: www.cell.com/neuron/fulltext/S0896-6273(19)30637-3