Previously, we demonstrated that reproductive senescence in female triple transgenic Alzheimer's (3×TgAD) mice was paralleled by a shift towards a ketogenic profile with a concomitant decline in mitochondrial activity in brain, suggesting a potential association between ovarian hormone loss and alteration in the bioenergetic profile of the brain. In the present study, we investigated the impact of ovariectomy and 17β-estradiol replacement on brain energy substrate availability and metabolism in a mouse model of familial Alzheimer's (3×TgAD). Results of these analyses indicated that ovarian hormones deprivation by ovariectomy (OVX) induced a significant decrease in brain glucose uptake indicated by decline in 2-[(18)F]fluoro-2-deoxy-D-glucose uptake measured by microPET-imaging. Mechanistically, OVX induced a significant decline in blood-brain-barrier specific glucose transporter expression, hexokinase expression and activity. The decline in glucose availability was accompanied by a significant rise in glial LDH5 expression and LDH5/LDH1 ratio indicative of lactate generation and utilization. In parallel, a significant rise in ketone body concentration in serum occurred which was coupled to an increase in neuronal MCT2 expression and 3-oxoacid-CoA transferase (SCOT) required for conversion of ketone bodies to acetyl-CoA. In addition, OVX-induced decline in glucose metabolism was paralleled by a significant increase in Aβ oligomer levels. 17β-estradiol preserved brain glucose-driven metabolic capacity and partially prevented the OVX-induced shift in bioenergetic substrate as evidenced by glucose uptake, glucose transporter expression and gene expression associated with aerobic glycolysis. 17β-estradiol also partially prevented the OVX-induced increase in Aβ oligomer levels. Collectively, these data indicate that ovarian hormone loss in a preclinical model of Alzheimer's was paralleled by a shift towards the metabolic pathway required for metabolism of alternative fuels in brain with a concomitant decline in brain glucose transport and metabolism. These findings also indicate that estrogen plays a critical role in sustaining brain bioenergetic capacity through preservation of glucose metabolism.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608536 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059825 | PLOS |
J Transl Med
January 2025
Ophthalmic Center, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
Background: The activation of macrophages or microglia in patients' whole body or local eyes play significant roles in diabetic retinopathy (DR). Mitochondrial function regulates the inflammatory polarization of macrophages. Therefore, the common mechanism of mitochondrial related genes (MRGs) and macrophage polarisation related genes (MPRGs) in DR is explored in our study to illustrate the pathophysiology of DR.
View Article and Find Full Text PDFBMC Endocr Disord
January 2025
Department of Endocrine and Metabolic Diseases, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, No. 185, Juqian Street, Changzhou, 213000, Jiangsu, China.
Background: Microwave ablation is a new, minimally invasive technique for the treatment of thyroid nodules. Hyperthyroidism due to destructive thyroiditis is a known risk of microwave ablation, though it occurs in only a minority of cases. We report a rare case of a patient diagnosed with Graves' disease nearly six months after undergoing microwave ablation of a thyroid nodule.
View Article and Find Full Text PDFInflamm Res
January 2025
Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, 610041, People's Republic of China.
Background: A significant association between immune cells and sepsis has been suggested by observational studies. However, the precise biological mechanisms underlying this association remain unclear. Therefore, we employed a Mendelian randomization (MR) approach to investigate the causal relationship between immune cells and genetic susceptibility to sepsis, and to explore the potential mediating role of blood metabolites.
View Article and Find Full Text PDFCommun Biol
January 2025
Georgia Cancer Center, Augusta University, Augusta, GA, 30912, USA.
The transsulfuration (TSS) pathway is an alternative source of cysteine for glutathione synthesis. Little of the TSS pathway in antioxidant capacity in sickle cell disease (SCD) is known. Here, we evaluate the effects of TSS pathway activation through cystathionine beta-synthase (CBS) to attenuate reactive oxygen species (ROS) and ferroptosis stresses in SCD.
View Article and Find Full Text PDFFunct Integr Genomics
January 2025
Intelligent OMICS Limited, Nottingham, United Kingdom.
Gene‒gene interactions play pivotal roles in disease pathogenesis and are fundamental in the development of targeted therapeutics, particularly through the elucidation of oncogenic gene drivers in cancer. The systematic analysis of pathways and gene interactions is critical in the drug discovery process for various cancer subtypes. SPAG5, known for its role in spindle formation during cell division, has been identified as an oncogene in several cancers, although its specific impact on AML remains underexplored.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!