Traumatic brain injury (TBI) accounts for more than 90,000 newly disabled persons annually in the USA with the upsurge in metabolic neuropathologies increasingly recognized to worsen outcomes. It is an alarming public health issue that more than 40% of the American population is affected by some metabolic disorder such as diabetes and obesity. Metabolic disorders are a risk factor for increased morbidity and predictors of death of TBI patients, and high sugar consumption, particularly fructose, is emerging as a main cause of metabolic disorders. Our preliminary results indicate that consumption of fructose disturbs important parameters of brain plasticity and can worsen the pathology of TBI. We would like to pursue these findings further to determine mechanisms by which fructose influences the capacity of the brain to cope with trauma. For example, the question as to whether fructose has direct effects on brain metabolism and cognitive function is largely uncharted, but the implications are paramount to employing strategies to enhance TBI recovery. Currently, insufficient understanding of how altered cellular metabolism affects brain function has limited the development of preventive programs and treatments. We have embarked on studies in rodents to determine crucial mechanisms by which metabolic perturbations disrupt the substrates for brain plasticity and function, underlying cognition. We will investigate the hypothesis that metabolic alterations carried by fructose impact important aspects of neuronal function and plasticity, which underlie cognitive performance (learning and memory) and emotional health (anxiety-like behaviors). Studies are also intended to obtain novel information how TBI influences main aspects of the metabolism of fructose in the brain, including fructose transporter, enzymatic activity, and metabolites. Although oxidative metabolism and plasma membrane homeostasis are inter-related events, this interaction is often overlooked. We will examine the concept that the plasma membrane is the main gate for transmission of information across the CNS, which can be damaged by the effects of fructose thereby reducing the threshold for the negative consequences of TBI. We will determine the capacity of dietary docosahexaenoic acid (DHA) to counteract the effects of fructose on synaptic plasticity and membrane function after TBI. DHA is a main component of the membrane; therefore, DHA has the magnificent power to regulate all forms of interneuronal signaling and the course of TBI. The successful completion of this proposal relies on our unique expertise in mechanisms by which metabolic challenges affect the substrates of brain plasticity and repair. We expect that mechanistic information provided by these interdisciplinary studies can nurture a new line of thought with regards to the menace of metabolic challenges on TBI and other neurological disorders, and foster new potential treatments.
The increasing consumption of fructose in the modern society poses a heavy threat to brain function, repair and the capacity to resist neurological disorders. We propose to determine mechanisms by which fructose consumption can worsen the outcome of TBI over time by integrating concepts of cellular bioenergetics, synaptic plasticity, and behavior. We also propose the use of omega-3 fatty acids to counteract the effects of fructose on TBI.
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