Mitochondrial Movement and Number Deficits in Embryonic Cortical Neurons from 3xTg-AD Mice
| Autor: | James W. Simpkins, Nadia Ahmed, John Z. Cavendish, Saumyendra N. Sarkar, Elizabeth B. Engler-Chiurazzi, Brishti A. White, Mark A. Colantonio, Dominic D. Quintana |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Agonist medicine.drug_class Mice Transgenic Disease Hippocampal formation Biology Mitochondrial Size Mitochondrial Dynamics Article Pathogenesis Mice 03 medical and health sciences 0302 clinical medicine Alzheimer Disease medicine Animals Receptor Pathological Cerebral Cortex Neurons General Neuroscience General Medicine Embryonic stem cell Mitochondria Disease Models Animal Psychiatry and Mental health Clinical Psychology 030104 developmental biology Geriatrics and Gerontology Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's Disease. 70:139-151 |
| ISSN: | 1875-8908 1387-2877 |
| Popis: | Mitochondrial dysfunction is often found in Alzheimer's disease (AD) patients and animal models. Clinical severity of AD is linked to early deficiencies in cognitive function and brain metabolism, indicating that pathological changes may begin early in life. Previous studies showed decreased mitochondrial function in primary hippocampal neurons from triple-transgenic Alzheimer's disease (3xTg-AD) mice and mitochondrial movement and structure deficits in primary neurons exposed to amyloid-β oligomers. The present study characterized mitochondrial movement, number, and structure in 3xTg-AD primary cortical neurons and non-transgenic (nonTg) controls. We found a significant reduction in mitochondrial number and movement in 3xTg-AD primary cortical neurons with modest structural changes. Additionally, application of the sigma-1 receptor agonist, (+)SKF-10,047, markedly increased mitochondrial movement in both 3xTg-AD and nonTg primary cortical cultures after one hour of treatment. (+)SKF-10,047 also led to a trend of increased mitochondrial number in 3xTg-AD cultures. Embryonic mitochondrial movement and number deficits could be among the key steps in the early pathogenesis of AD that compromise cognitive or metabolic reserve, and amelioration of these deficits could be a promising area for further preclinical and clinical study. |
| Databáze: | OpenAIRE |
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