There is evidence providing a strong rationale that Curcumin (a natural phenol and the principal curcuminoid of the spice turmeric and a member of the ginger family), through its antiinflammatory and antioxidative properties, can slow down or delay the process of senescence as well as the onset or progression of many age-related diseases. Rhesus monkeys, similar to humans, undergo a cognitive decline as a function of age. Studies conducted with electron microscopy point to alterations that are most likely more pronounced in white matter, than in gray matter, and involve axonal myelin breakdown, likely initiated by the activation of microglia. Although whether these changes are localized or diffused, and what is their time course, still remains unknown with certainty, there is accruing evidence that frontal lobe circuitry is principally affected. Histological examination, while providing very high resolution microstructural data well characterizing local specificity of brain changes, cannot be performed on large populations, nor can it be easily used in a longitudinal study design, making it quite difficult to understand behavioral or metabolic consequences of specific, localized microstructural changes, and follow them over time. The purpose of this new R21 is to assess, following a cross-sectional design and using state of the art MR technologies, structural and metabolic changes related to Curcumin intervention in frontal circuity in cognitively aging rhesus monkeys. More specifically, 18 middle aged rhesus monkeys (9 treated with Curcumin and 9 with placebo), which are part of an already funded larger Boston University study (Dr. Mark Moss, PI) will undergo two additional, unique MR sessions. Diffusion MR data will be obtained at the Skyra Connectome scanner, where we will collect high definition free water imaging (biomarker sensitive to neuroinflammation). MR Spectroscopy will be obtained at the 7T magnet, where maps of glutathione and taurine (antioxidative metabolites) will be acquired. This imaging data will be collected 2 years into Curcumin treatment, and combined with cognitive data, to investigate structural and metabolite changes in frontal circuity. Finally, since these monkeys are subsequently euthanized by perfusion fixation of the brain and processed so that whole brain series of sections cryoprotected at -80 degrees C are available for histological correlation, histological validation of neuroimaging biomarkers will be also possible. Data collected here will serve as preliminary for a following RO1 application.
There is evidence providing a strong rationale that Curcumin (a natural phenol, the principal curcuminoid of the spice turmeric and a member of the ginger family) can slow down or delay the process of senescence as well as the onset or progression of many age-related diseases. Using a cross-sectional design and specific imaging biomarkers for neuroinflammation and oxidative stress, we propose to study neurobiological correlates of Curcumin intervention related to cognitive changes in rhesus monkeys. Our study is designed to benefit from availability of animals already undergoing intervention and availability of histologicl data, in efforts to provide imaging and metabolic characterization of curcumin treatment and gain insight into how to slow down the neurobiology of cognitive aging (transferable to humans).
