Ketamine potential tool to treat stress-related illness

Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI), researchers at Uppsala University and Karolinska Institutet show how the drug ketamine enhances our stress resilience by modulating our brain's dorsal raphe nucleus - an area crucial for serotonin signaling that affects our mood and emotions. The study further highlights the protein p11's central role in these effects, thus providing important clues to potential treatments for stress-related diseases.

“MALDI-MSI enables detailed mapping of signaling substances and metabolites in the dorsal raphe nucleus, and our results clearly illuminate how stress affects tryptophan metabolism, with ketamine restoring the balance. Using this information, we were able to link the molecular changes to serotonergic neurons and establish the dependence on the p11 protein,” states Per Andrén, Professor of Mass Spectrometry Imaging.

The results also contribute to showcase the major importance of MALDI-MSI technology for studies of brain mechanisms and the development of precision medicine for stress-related diseases

“MALDI-MSI technology enables the analysis of molecular changes in relation to functional effects, which deepens our understanding of how ketamine influences stress resilience and depression,” say Anna Nilsson and Reza Shariatgorji, Associate Professor at the Department of Pharmaceutical Biosciences and co-authors of the article that is published in Molecular Psychiatry.

text: Magnus Alsne, photo: Mikael Wallerstedt a o