CNS sirtuins in radiation-induced vascular permeability and neurodegeneration

Division Of Basic Sciences - Nci

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Abstract

Our laboratory has identified a novel mechanism to prevent radiation-induced changes in dendritic plasticity which preserves memory function following radiation exposures. These ongoing studies are investigating the relationships signaling in neurons, astrocytes, and microglia, and how radiation influences changes in glial crosstalk that lead to cognitive dysfunction. These studies, originally performed in vitro, have extended to our novel animal model which demonstrates resistance to radiation-induced brain injury as well as correlative analyses in patient specimens evaluating radiation dose in relation to modifiable radiation-induced subcellular signaling alterations. Additionally, these changes are being evaluated with pharmaceutical agents radiation mitigators to determine possible molecular targets of interest to preserve cognition following radiation-induced neurologic injury. These findings are critical to the understanding of the fundamental regulation of dendritic plasticity and memory and has significant potential application in conditions where dendritic plasticity is altered such as Alzheimer's, Parkinson's, attention deficit hyperactivity disorder and autism spectrum disorders, as well as instances of elevated radiation exposures such as potential space travel.