Aug 6, 2024
New method tracks how psychedelics affect neurons in minutes
Posted by Saúl Morales Rodriguéz in categories: biotech/medical, neuroscience
Researchers at the University of California, Davis have developed a rapid, noninvasive tool to track the neurons and biomolecules activated in the brain by psychedelic drugs. The protein-based tool, which is called Ca2+-activated Split-TurboID, or CaST, is described in research published in Nature Methods.
There has been mounting interest in the value of psychedelic-inspired compounds as treatments for brain disorders including depression, post-traumatic stress disorder and substance use disorder. Psychedelic compounds like LSD, DMT and psilocybin promote the growth and strengthening of neurons and their connections in the brain’s prefrontal cortex. The new tool could help scientists unlock the benefits of psychedelic treatments for patients with brain disorders.
“It’s important to think about the cellular mechanisms that these psychedelics act upon,” said Christina Kim, an assistant professor of neurology at the UC Davis Center for Neuroscience and School of Medicine, and an affiliate of the UC Davis Institute for Psychedelics and Neurotherapeutics. “What are they? Once we know that, we can design different variants that target the same mechanism but with fewer side effects.”
The ability to accurately quantify biological age could help monitor and control healthy aging. Epigenetic clocks have emerged as promising tools for estimating biological age, yet so far, most of these clocks have been developed from heterogeneous bulk tissues, and are thus composites of two aging processes, one reflecting the change of cell-type composition with age and another reflecting the aging of individual cell-types. There is thus a need to dissect and quantify these two components of epigenetic clocks, and to develop epigenetic clocks that can yield biological age estimates at cell-type resolution. Here we demonstrate that in blood and brain, approximately 35% of an epigenetic clock’s accuracy is driven by underlying shifts in lymphocyte and neuronal subsets, respectively. Using brain and liver tissue as prototypes, we build and validate neuron and hepatocyte specific DNA methylation clocks, and demonstrate that these cell-type specific clocks yield improved estimates of chronological age in the corresponding cell and tissue-types. We find that neuron and glia specific clocks display biological age acceleration in Alzheimer’s Disease with the effect being strongest for glia in the temporal lobe. The hepatocyte clock is found accelerated in liver under various pathological conditions. In contrast, non-cell-type specific clocks do not display biological age-acceleration, or only do so more marginally. In summary, this work highlights the importance of dissecting epigenetic clocks and quantifying biological age at cell-type resolution.
