Affiliations: [a] Department of Neuroscience, Center for Basic and Translational Stroke Research, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA
| [b] Department of Physiology and Pharmacology, Center for Basic and Translational Stroke Research, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA
Correspondence:
[*]
Correspondence to: James W. Simpkins, PhD, Department of Physiology and Pharmacology, West Virginia
University School of Medicine, 64 Medical Center Drive, Morgantown WV 26501, USA. Tel.: +1 304 293 7430;
E-mail: jwsimpkins@hsc.wvu.edu.
Abstract: 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.
