MBB Cluster event: Probing the molecular underpinnings of early cognitive decline

Dr Santiago Rompani from the European Molecular Biology Laboratory, Rome, will join the Mind, Brain & Behaviour Research Cluster for an informal talk/discussion on “Probing the molecular underpinnings of early cognitive decline”. All members of the College and members of Common Room are welcome.

Abstract:
The brain’s ability to drive optimal responses and react to stimuli is at a peak early in life, and while decline later in life, from the age of 60, is the most dramatic, decline in most cognitive domains starts much earlier, for many domains as early as the age of 20. Studying the molecular mechanisms of this early decline in mice is challenging, since the very initial, proximal causes of this decline are likely subtle, and quantifying animal behavior can be very variable and difficult to compare to human cognitive ability. Currently, the field deals with this difficulty by comparing very young to very old animals, equivalent to comparing human 20-year-olds to 60-year-olds. We propose that using a battery of ethologically-relevant behaviors allows us to detect cognitive decline far earlier, in animals equivalent to a human 30 and 40-year-old, or a 6-month-old animal compared to a 10-month-old one. We find a dramatic difference in not only motor decline, but also qualitative changes in curiosity-driven exploration in a complex maze, cricket hunting performance, and anxiety-like behaviors in an open field. We pair these behavioral data with RNAseq profiling of a subset of T cells in the blood that have been previously described to decline with age, together with other blood-derived hallmarks of aging, like the epigenetic clock. While analysis of these data is ongoing, we find that there is a significant senescence of naïve T cells between animals aging from 6 to 10 months old, suggesting our behavioral readout is capturing true age-related decline, not a maturation process. In conclusion, we suggest a novel model for tackling the molecular underpinnings of aging in the brain, focusing on the earliest detectable stages of decline, in order to obtain a more causal understanding of the process, and ultimately treat it.