Grants and Contracts Details
The research objective of this proposal is to use high-field MRI/MRS and PET to investigate the brain integrity of aging mice and identify possible protective effects of caloric restriction (CR). CR is the most studied anti-aging manipulation and has been shown to increase the lifespan of a broad range of species. Although CR shows to attenuate the age-related decline in a variety of physiological functions, the effect of CR on brain metabolism and function has not been well-characterized, especially with non-invasive neuroimaging methods. The purpose of the study is to characterize the effect of CR on in vivo brain metabolic, hemodynamic, structural and functional integrity in aging using multimodal neuroimaging methods, and the association of the neuroimaging indices with the cognitive testing. The central hypothesis of this proposal is that cerebral metabolic function will decline in normal aging and consequently reduce brain structural, functional and cognitive integrity; mice with CR intervention will demonstrate: preserved cerebral metabolic rate of glucose (CMRGlc) and oxygen (CMRO2), cerebral blood flow (CBF) and total ATP concentration; and, thus preserved brain structure, functional connectivity, and cognition during aging. The hypothesis will be tested by pursuing two specific aims: 1) Determine effects of normal aging on brain metabolic and hemodynamic integrity and possible protective effects of CR; and, 2) Determine effects of normal aging on structural and functional integrity and possible protective effects of CR. Upon completion of the two Aims, the covariance of the imaging indices and the cognitive results (obtained with Morris Water Maze and Passive Avoidance Performance by Dr. Galvan, a collaborator of this project) will be determined. The approach is innovative, because it investigates the CR protective effect on in vivo brain metabolism in aging process with non-invasive neuroimaging methods; it uses complementary, multi-parametric, non-invasive imaging methods (MRI, MRS and PET) to explore the physiological effects of mitochondrial alterations, for the first time; it uses quantitative imaging techniques at ultra-high field (11.7T) and in rodents, the first time this has been done; and, it will be the first study to investigate the correlation between cognitive effects (memory and spatial information processing) and brain imaging results in the CR mouse model. The proposed research is significant because 1) physiological effects of metabolic alterations in aging and age-related neuronal disorders, disease progression and treatment efficacy can be monitored non-invasively and nondestructively; 2) the interplay between brain metabolic, structural and cognitive functions in aging can be identified; and, 3) these multi-metric imaging methods can be translated seamlessly from rodents to non-human primates and to humans.
|Effective start/end date||4/1/14 → 12/31/14|