Adipose inflammation mediates obesity-induced deficits in hippocampal plasticity

Project: Research project

Description

The broad, long-term objective of the proposed research is to identify the underlying mechanisms for the
increased susceptibility to age-related cognitive decline and dementia in obesity and diabetes. This objective
will be addressed through a series of experiments in two mouse models of obesity arising from diet or genetic
manipulation. The central hypothesis is that fat is a source of inflammatory cytokines that impair cognition by
inducing local inflammation in the hippocampus, a brain region involved in learning and memory. While the
brain is normally protected from systemic inflammation, the protective barrier between blood and brain is
compromised in obesity, and the goal of these studies is to determine what blood-borne signal contributes to
cognitive impairment in obesity and diabetes. These experiments are relevant to the goals of the National
Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) because of the focus on inflammation in obesity
and diabetes, and the implications of increased inflammation for cognition in individuals suffering from these
debilitating conditions. The proposed studies will take place in the Physiology Department at the Medical
College of Georgia, which has an institutional track record of excellence in diabetes and obesity research. The
environment is extraordinarily supportive and conducive to the research career development plan described in
the current application, which includes didactic and experimental approaches to further the candidate's goal of
establishing an independent research program in neuroimmunology. The rationale for additional training under
this award is twofold: first, the candidate has demonstrated excellence in neuroendocrinology, but has no
experience with the methods and theories of immunology, therefore in order to pursue the studies in this
proposal, additional training is required; and second, although the candidate currently holds an Assistant
Professorship, the short duration of the candidate's postdoctoral training (2 years) means that additional time
and training will be required in order to establish a productive research program in neuroimmunology. The
candidate's immediate career goal is to establish an externally funded research program and demonstrate
independence in publications. Over the long term, the candidate hopes to conduct research that identifies
molecular mediators linking metabolism and immune function with cognition. By building a bridge between
diabetes and obesity and the field of learning and memory research, it may be possible to develop
personalized interventions to prevent increased rates of cognitive impairment and dementia in individuals with
metabolic syndrome features.
StatusFinished
Effective start/end date9/6/136/30/16

Funding

  • National Institutes of Health: $955.00
  • National Institutes of Health: $122,515.00
  • National Institutes of Health: $122,515.00
  • National Institutes of Health: $122,515.00

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Obesity
Inflammation
Research
Cognition
Dementia
Hope
Neuroendocrinology
Learning
National Institute of Diabetes and Digestive and Kidney Diseases (U.S.)
Allergy and Immunology
Blood-Brain Barrier
Brain
Publications
Hippocampus
Fats
Cytokines
Diet
Cognitive Dysfunction

ASJC

  • Medicine(all)