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Cumulative and Persistent Changes in the Brain in Response to Stress and Aging


The brain has a remarkable capacity for plasticity: it physically encodes lived experiences within itself, and so is constantly sculpted and shaped by the environment. On short time scales, specific experiences and events are embedded as structural changes at the level of the synapse – in other words, memory. Over longer time scales, other forms of plasticity are involved in causing cumulative and persistent structural changes that do not necessarily represent specific information or experiences per say, but rather influence the overall behavioral mode of the organism. Such changes are not limited to the synapse, but rather may involve broad changes in the cellular composition and structure of the brain. This work seeks to characterize such mechanisms of long-lasting plasticity, focusing on two major areas. Firstly, we investigate how chronic stress affects the cell fate of neural stem cells in the adult hippocampus to cause an increase in the production oligodendrocytes and a decrease in neurons. By changing the cellular composition of the hippocampus, this shift towards oligodendrogenesis may provide a structural basis for long-lasting changes in mood and behavior that can occur after stressful experiences. Secondly, we investigate biological changes in the aging brain, seeking to uncover mechanisms that are involved in cognitive decline. We find that aging involves a loss of integrity of the vascular blood-brain barrier, which allows molecules from the blood to enter into the brain. In turn, this triggers an inflammatory response the causes neural dysfunction and induces cognitive decline. Together, these studies seek to broaden the time scales on which we observe and characterize brain plasticity. By understanding persistent changes that accumulate in the brain over months or years, we may provide new insights into complex neurological diseases that manifest slowly in response to lifestyle risk factors, and ultimately develop new, more effective treatments.

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