Hybrid seminar: both in presence (max 25 people in Seminar room!!!) and on webex
Thursday 30/11/23 h. 2:00 pm - Hybrid Seminar Elif Keshinoz, Department of Anatomy, School of Medicine, Acibadem Mehmet Ali Aydinlar University - Istanbul, Turkey. Mitochondrial alterations in Alzheimer’s Disease: Insights from the 3xTg Model
Aim: The 3xTg mouse model mimics key features of Alzheimer's disease (AD) through APP, PS1, and tau mutations. Mitochondrial dysfunction in AD results from interactions between these genes, leading to Aβ and tau deposits, damaging mitochondria, generating ER stress, and resulting in decreased ATP production, impaired neurons, and cell death. Mitochondrial dysfunction also leads to oxidative stress, inflammation, and the formation of amyloid plaques and neurofibrillary tangles, contributing to AD pathology. Mitochondria-ER contact sites (MERCs) are essential for cellular functions, including calcium signaling, lipid metabolism, and molecule exchange across organelles. An alteration may impact cellular calcium regulation, mitochondrial function, and Alzheimer's pathogenesis. The study aims to investigate the role of mitochondrial alteration and MERCs in the 3xTg mice model of AD.
Materials and Methods: In this study, electron microscopic images of brain tissues from the CA3 regions of the hippocampus were taken at 10,000X magnification in 3xTg and Wild Type mice at 3, 8 and 12 months of age. Learning and memory deficits emerged at 3 months in the 3xTg mouse model, while cellular damage detectable through light microscopy became evident after 12 months. Various parameters were assessed to understand mitochondrial dynamics and morphology alterations. The images identified changes in mitochondrial architecture, such as mitochondrial number, area, and average widths. Additionally, the distance between mitochondria-endoplasmic reticulum contact sites (MERCs) was measured.
Results: Biophysical changes observed in mitochondrial architecture and MERCs shed light on the spatial organization and interactions between mitochondria and the endoplasmic reticulum. This biophysical analysis provides key clues for understanding changes in calcium signaling and cellular communication that affect mitochondrial dynamics and morphology in the CA3 region.
Conclusion:Understanding the complicated link between mitochondrial structure and MERCs in the 3xTg model could aid in the treatment of Alzheimer's disease via therapies aimed at protecting mitochondrial function.
