Effects of Mild Excitotoxic Stimulus on Mitochondria Ca2+ Handling in Hippocampal Cultures of a Mouse Model of Alzheimer’s Disease
| Autor: | Emy Basso, Giulia Rigotto, Tullio Pozzan, Lorena Zentilin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cell signaling
hippocampus QH301-705.5 Cell Excitotoxicity Mitochondrion Stimulus (physiology) Biology medicine.disease_cause medicine Ca2+ Biology (General) chemistry.chemical_classification Reactive oxygen species Neurodegeneration General Medicine medicine.disease mitochondria medicine.anatomical_structure chemistry membrane potential Alisporivir Neuroscience Alzheimer’s disease excitotoxicity Intracellular |
| Zdroj: | Cells, Vol 10, Iss 2046, p 2046 (2021) Cells Volume 10 Issue 8 |
| ISSN: | 2073-4409 |
| Popis: | In Alzheimer’s disease (AD), the molecular mechanisms involved in the neurodegeneration are still incompletely defined, though this aspect is crucial for a better understanding of the malady and for devising effective therapies. Mitochondrial dysfunctions and altered Ca2+ signaling have long been implicated in AD, though it is debated whether these events occur early in the course of the pathology, or whether they develop at late stages of the disease and represent consequences of different alterations. Mitochondria are central to many aspects of cellular metabolism providing energy, lipids, reactive oxygen species, signaling molecules for cellular quality control, and actively shaping intracellular Ca2+ signaling, modulating the intensity and duration of the signal itself. Abnormalities in the ability of mitochondria to take up and subsequently release Ca2+ could lead to changes in the metabolism of the organelle, and of the cell as a whole, that eventually result in cell death. We sought to investigate the role of mitochondria and Ca2+ signaling in a model of Familial Alzheimer’s disease and found early alterations in mitochondria physiology under stressful condition, namely, reduced maximal respiration, decreased ability to sustain membrane potential, and a slower return to basal matrix Ca2+ levels after a mild excitotoxic stimulus. Treatment with an inhibitor of the permeability transition pore attenuated some of these mitochondrial disfunctions and may represent a promising tool to ameliorate mitochondria and cellular functioning in AD and prevent or slow down cell loss in the disease. |
| Databáze: | OpenAIRE |
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