Gjumrakch Aliev
GALLY†International Biomedical Research Institute Inc., San Antonio, TX, USA
Title: Implication of the Multitarget Therapies in the Context of the Aged Associated Oxidative Stress Induced Cellular and Subcellular Hypoperfusion, and Mitochondrial DNA deletion During the Development and Maturation of Alzheimer Disease: past present future
Biography
Biography: Gjumrakch Aliev
Abstract
Background and Hypothesis: Oxidative stress induced cerebral hypoperfusion and mitochondrial failure appears to be a key pathogenic factor in the development of age-associated diseases, triggering mild cognitive impairment and eventual conversion to Alzheimer disease (AD). Mitochondrial integrity is associated with cellular viability.
Goal: We studied cellular and subcellular features of hippocampal neurons and microvessel mitochondrial lesions, oxidative stress markers and protein immunoreactivity in animal models that mimic MCI and/or AD. In addition, we studied the effects of dietary antioxidant treatment on neuronal mitochondrial ultrastructure in rats. The goals of the proposed study are to determine the role of mitochondria failure and neuronal damage during the maturation of AD-like pathology in rats and transgenic mice overexpressing either amyloid β precursor protein (AßPP).
Methods: In this project we applied the following methods: transmission electron microscopy (TEM) qualitative analysis; EM pre-embedding immunogold cytochemistry using probes for human wild type, 5kb deleted and mouse mtDNA and antibodies against cytochrome c oxidase. Quantitative morphometric analysis of the degree of mitochondrial lesions.
Summary of Results: there was a significantly higher degree of mitochondrial damage and mitochondrial DNA overproliferation and deletion in neurons and cerebrovascular wall cells in transgenic mice and aged untreated rats in comparison to age-matched controls and non-treated subjects. Mitochondrial abnormalities are associated with atherosclerotic lesions of brain microvessels.
Conclusion: based on this results our conclusion is that changes in mitochondrial morphology and mitochondrial DNA coexist with metabolic dysfunction in AD mice and age-associated neurodegeneration and may serve as diagnostic markers and treatment targets