Psychedelic-induced proteome changes in rodent brain regions

In recent decades, significant progress has been made in the field of psychedelics research. However, the short- and long-term cellular responses to psychedelics at the level of proteome remodeling remain largely unexplored. In this study, we utilized a rodent model to investigate alterations in the proteome of four brain regions involved in the response to psychedelic administration, including psilocybin.

Psychedelic substances, including psilocybin, were administered to rodents at doses consistent with those reported in the literature as acute dosages, mirroring their application in psychotherapy. Animals were sacrificed, and their brains were promptly extracted, snap-frozen, and sectioned using a cryotome, and the selected brain regions were isolated. The tissues were processed, digested, and analyzed using an ultra-high-performance liquid chromatography (uHPLC) system coupled with a ThermoScientific Tribrid Orbitrap mass spectrometer. Data was collected in data-independent acquisition (DIA) mode and analyzed using PEAKS and FragPipe software.

Our preliminary data highlight specific changes in protein abundance that are intricately tied to distinct brain regions. Notably, these alterations are predominantly observed in structural and membrane proteins, underscoring their significance in the context of our study. The lack of comprehensive proteomics research in this area emphasizes the need for further investigations to enhance the identification of membrane proteins within our samples.

An intriguing aspect of our findings is the annotation of proteins exhibiting increased levels, which suggests a potential induction of neural plasticity. These observed changes may be linked to associations with receptors commonly involved in long-term potentiation (LTP), a crucial mechanism underlying learning and memory processes. Furthermore, these proteins may interact with other molecules integral to neural plasticity, indicating a complex network of interactions that warrant further investigation to elucidate their precise role in psychedelics-induced alterations in brain proteomics.