Friday, April 4, 2025
4/4/2025
An investigation of hyperglycemia-induced region-specific changes in brain metabolism and behavior - Project Summary Depression remains one of the leading causes of disability worldwide. Despite the number of pharmacological interventions, approximately one-third of patients are treatment resistant. The variability in treatment response suggests that there is diversity in the pathophysiological mechanisms of depression. Therefore, improving response rates will require a better understanding of their distinct pathophysiology and then personalize treatment. One proposed depressive subtype is immuno-metabolic depression. This is characterized by elevated levels of peripheral inflammation and increased expression of neurovegetative symptoms. This subtype may encompass up to 25% of all depressive cases. Individuals with chronic disease, such as diabetes and cardiovascular disease, are more likely than the general population to develop depression and are more likely to fall into this “immuno-metabolic” category. While there are descriptive studies on this depressive subtype, empirical studies directly examining the relationship between inflammation, metabolic dysfunction, and behavior in a region-specific manner are limited. Within this grant we aim to identify the region-specific changes in brain metabolism in two models of hyperglycemia and to evaluate behavioral domains associated with these brain regions. We propose to use multiple levels of region-specific tissue analyses including mitochondrial structure, mitochondrial function, and gene transcriptional changes related to inflammation and metabolism. We hypothesized that chronic hyperglycemia will induce region-specific neuroinflammation, mitochondrial dysfunction, and behavioral changes. We will focus on the hypothalamus, amygdala, basal ganglia, cerebellum, and auditory cortex as these regions represent areas with high and low expression of glucose sensing neurons. The proposed studies will provide novel insights into the mechanisms underlying immuno-metabolic depressive and may inform future personalized therapeutic interventions. These studies will also engage undergraduate students in meritorious research, helping to foster their enthusiasm for biomedical research careers.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).