Selected Grantee Publications
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- 4 results found
- Rodent Models
- T35
The Role of ATP Citrate Lyase in Myelin Formation and Maintenance
Schneider et al., Glia. 2024.
https://pubmed.ncbi.nlm.nih.gov/39318247/
Myelin formation by Schwann cells is critical for peripheral nervous system development and long-term neuronal function. The study examined how acetyl coenzyme A (acetyl-CoA), essential for lipid synthesis in myelin, is derived, with a focus on mitochondrial ATP citrate lysate (ACLY). By using both sexes in a Schwann cell–specific ACLY knockout mouse model, the authors reported that ACLY plays a role in acetyl-CoA supply for myelin maintenance but not myelin formation. ACLY is necessary for sustaining myelin gene expression and preventing nerve injury pathways. This work highlights a unique dependency on mitochondrial acetyl-CoA for Schwann cell integrity, providing insights into lipid metabolism in neuronal repair. Supported by ORIP (T35OD011078), NICHD, and NINDS.
Sex-Specific Cardiac Remodeling in Aged Rats After Adolescent Chronic Stress: Associations with Endocrine and Metabolic Factors
Dearing et al., Biology of Sex Differences. 2024.
https://pubmed.ncbi.nlm.nih.gov/39180122
Cardiovascular disease is a leading cause of death in the world. The potential effects of chronic stress on the development and progression of cardiovascular disease in the aged heart are unknown. In this study, researchers investigated sex- and stress-specific effects on left ventricular hypertrophy (LVH) after aging. Male and female rats were exposed to chronic stress during adolescence and then challenged with a swim test and a glucose tolerance test before and after aging 15 months. As a group, female rats showed increased LVH in response to early life stress. Male rats showed individual differences in vulnerability. These results indicate that sex and stress history can interact to determine susceptibility to cardiovascular risks. Supported by ORIP (F30OD032120, T35OD015130) and NHLBI.
A Novel TGFβ Receptor Inhibitor, IPW-5371, Prevents Diet-induced Hepatic Steatosis and Insulin Resistance in Irradiated Mice
Szalanczy et al., Radiation Research. 2024.
https://pubmed.ncbi.nlm.nih.gov/38772553
Radiation damages adipose progenitor cells and increases liver fibrosis, leading to the development of metabolic-associated fatty liver disease (MAFLD) and insulin resistance. As the number of cancer survivors increases and the risk of accidental radiation exposure rises, there is a pressing need to characterize and mitigate the delayed effects of radiation exposure. Some of these effects are mediated by TGFβ pathway signaling, which increases in response to radiation exposure and causes fibrosis. In this study, IPW-5371—a small-molecule inhibitor of a TGFβ receptor called activin receptor-like kinase 5 (ALK5)—was shown to protect mice from the effects of sublethal whole-body irradiation and chronic consumption of a Western diet. Mice treated with IPW-5371 exhibited lower fibrosis and fat accumulation in the liver, were more responsive to insulin, and had lower circulating triglycerides and better muscle endurance. IPW-5371 is a promising treatment for mitigating the metabolic effects of radiation exposure and preventing MAFLD. Supported by ORIP (T35OD010946, T32OD010957).
Loss of Lymphatic IKKα Disrupts Lung Immune Homeostasis, Drives BALT Formation, and Protects Against Influenza
Cully et al., Immunohorizons. 2024.
https://pubmed.ncbi.nlm.nih.gov/39007717/
Tertiary lymphoid structures (TLS) have context-specific roles, and more work is needed to understand how they function in separate diseases to drive or reduce pathology. Researchers showed previously that lymph node formation is ablated in mice constitutively lacking IκB kinase alpha (IKKα) in lymphatic endothelial cells (LECs). In this study, they demonstrated that loss of IKKα in lymphatic endothelial cells leads to the formation of bronchus-associated lymphoid tissue in the lung. Additionally, they showed that male and female mice challenged with influenza A virus (IAV) exhibited markedly improved survival rates and reduced weight loss, compared with littermate controls. They concluded that ablating IKKα in this tissue reduces the susceptibility of the mice to IAV infection through a decrease in proinflammatory stimuli. This work provides a new model to explore the mechanisms of TLS formation and the immunoregulatory function of lung lymphatics. Supported by ORIP (T35OD010919), NHLBI, NIAID, and NIAMS.