Jefferson Frisbee, Ph.D.
Ting-Yim Lee Endowed Chair & Professor, Department of Medical Biophysics
Schulich School of Medicine & Dentistry, Western University
“Cerebral Vasculopathy and Depressive Symptoms with Metabolic Disease: the Impact of Sex and Informed Interventions.”
Previous study has suggested that reduced microvessel density and reactivity in the peripheral circulation with evolving metabolic disease severity represents a significant contributor to impaired skeletal muscle oxygenation and fatigue-resistance. Based on this and our recent work, we hypothesized that cerebral microvascular rarefaction and dysfunction arises from the increased pro-oxidant and pro-inflammatory environment with metabolic disease and is predictive of the severity of the emergence of depressive symptoms in obese Zucker rats (OZR). In OZR, cerebrovascular rarefaction followed the emergence of elevated oxidant and inflammatory environments that were characterized by an increased vascular production of TxA2. Subsequent emergence of depressive symptoms in OZR were correlated to the timing and severity of the rarefaction. Chronic therapy with anti-oxidant or anti-inflammation agents blunted the severity of both rarefaction and depressive symptoms, although overall effectiveness was constrained. Blockade of TxA2 production or action resulted in a stronger therapeutic effect, suggesting that vascular TxA2 production and action represents a significant contributor to rarefaction and the emergence of depressive symptoms with chronic metabolic disease (although other pathways clearly contribute as well). A de novo biosimulation of cerebrovascular oxygenation patterns in the face of progressive rarefaction demonstrates the increased probability of generation of hypoxic regions within the microvascular networks which may contribute to impaired neuronal metabolism and the emergence of depressive symptoms. The results to be discussed also implicate the potential importance of aggressive prodromic intervention in reducing the severity of chronic implications arising from metabolic disease.
Friday, March 17, 2023, 11:00AM-12:00PM, EAD-506
University of North Texas Health Science Center
Fort Worth, Texas