Event Type
Research Presentation
Academic Department
Biology
Location
Dana Science Building, 2nd floor
Start Date
25-4-2025 1:00 PM
End Date
25-4-2025 2:30 PM
Description
Under the direction of Dr. Michael Maniskas (The University of Texas Houston), Dr. Mary Jane Carmichael (Hollins University) Brain homeostasis is fundamental to normal neurological functions, as excess iron can trigger oxidative stress and contribute to cognitive deficits. Chronic cerebral hypoperfusion (CCH) has been reported to contribute to the physiopathology of vascular contributions to cognitive impairment and dementia (VCID). Iron accumulation has been reported to influence the progression of neurodegenerative diseases, such as Alzheimer’s disease (AD) and vascular dementia (VaD). This research project explores the impacts of CCH and iron overload on behavioral outcomes and iron metabolism in aged (17-18 months) C57BL/6 mice, analyzing male and female subjects separately. Both male and female mice were subjected to bilateral common carotid stenosis (BCAS) or sham surgery, followed by oral gavage of 5% ferric citrate or saline solution for six weeks. Behavioral tests, serum iron quantification, qPCR analysis, and Prussian blue staining were performed to assess motor activity, anxiety-like behavior, and gene expression of glutathione synthetase (GSS) and nuclear receptor coactivator 4 (NCOA4). CCH induces anxiety-like behavior and increases the expression of GSS and NCOA4, suggesting an oxidative stress response. BCAS significantly reduces serum iron levels, which aligns with reports of anemia in CCH patients. Notably, iron overload did not worsen the effects of BCAS, which suggests that these two conditions govern brain iron metabolism through different molecular mechanisms. Female mice showed significant iron accumulation in the brain compared to males in both iron overload and CCH models. These results suggest a sex-specific vulnerability to brain iron accumulation. Future research will explore oxidative stress markers and the molecular mechanisms underlying sex-based differences in brain iron metabolism.
Brain Iron Metabolism in Mouse Models of Cerebral Hypoperfusion and Iron Overload
Dana Science Building, 2nd floor
Under the direction of Dr. Michael Maniskas (The University of Texas Houston), Dr. Mary Jane Carmichael (Hollins University) Brain homeostasis is fundamental to normal neurological functions, as excess iron can trigger oxidative stress and contribute to cognitive deficits. Chronic cerebral hypoperfusion (CCH) has been reported to contribute to the physiopathology of vascular contributions to cognitive impairment and dementia (VCID). Iron accumulation has been reported to influence the progression of neurodegenerative diseases, such as Alzheimer’s disease (AD) and vascular dementia (VaD). This research project explores the impacts of CCH and iron overload on behavioral outcomes and iron metabolism in aged (17-18 months) C57BL/6 mice, analyzing male and female subjects separately. Both male and female mice were subjected to bilateral common carotid stenosis (BCAS) or sham surgery, followed by oral gavage of 5% ferric citrate or saline solution for six weeks. Behavioral tests, serum iron quantification, qPCR analysis, and Prussian blue staining were performed to assess motor activity, anxiety-like behavior, and gene expression of glutathione synthetase (GSS) and nuclear receptor coactivator 4 (NCOA4). CCH induces anxiety-like behavior and increases the expression of GSS and NCOA4, suggesting an oxidative stress response. BCAS significantly reduces serum iron levels, which aligns with reports of anemia in CCH patients. Notably, iron overload did not worsen the effects of BCAS, which suggests that these two conditions govern brain iron metabolism through different molecular mechanisms. Female mice showed significant iron accumulation in the brain compared to males in both iron overload and CCH models. These results suggest a sex-specific vulnerability to brain iron accumulation. Future research will explore oxidative stress markers and the molecular mechanisms underlying sex-based differences in brain iron metabolism.