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Effects of Melatonin and Beta‐Amyloid on Mitochondrial Function in a Model of Aging Mouse Astrocytes
Author(s) -
Debner Emily K,
King Jonathan M
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.702.1
Subject(s) - melatonin , neurodegeneration , neuroprotection , astrocyte , endocrinology , medicine , calcium , biology , mitochondrion , matrix metalloproteinase , microbiology and biotechnology , chemistry , neuroscience , central nervous system , disease
Background Astrocytes provide support for neurons, however, with age, astrocytes’ ability to provide neuroprotection decreases. This decrease in neuroprotection increases the likelihood of neurodegenerative diseases, that compromise function. One hallmark of neurodegeneration is accumulation of β‐amyloid (βA) plaques, which disrupts cellular function and often leads to cellular death. As astrocytes age, they have been shown to naturally have lower mitochondrial membrane potential (MMP) and more frequent with larger amplitude calcium waves. Treatment with melatonin has been shown to decrease βA production and prevent plaque formation in the brain, suggesting melatonin plays a role during neurodegeneration. The interplay between melatonin and βA effects on astrocyte function was examined by measuring MMP and calcium waves. Methods Primary mouse astrocyte cultures obtained from young (4 month) and old (28 month) animals were used in the current study. Astrocytes were cultured for 24hrs with 100μM melatonin before loading with either MitoID or Fluo3. Measures were obtained using galvano or resonant scanning modes on a confocal microscope system, respectively. Astrocytes were then treated with 0.5μM βA (AggreSure) and imaged for an additional 30 minutes. MMP and calcium waves were analyzed to indicate cellular stress and change in cellular function. Results Melatonin significantly elevated baseline MMP in young astrocytes while protecting MMP loss due to βA exposure. Baseline MMP levels were unaffected by melatonin in old astrocytes although melatonin preserved MMP levels during βA exposure. This suggests young astrocytes capacity to alter cellular activities due to melatonin exposure is more robust. Calcium waves in young astrocytes persisted for a longer duration during βA exposure. Conclusions These results indicate that melatonin has protective effects on preserving MMP in the presence of βA, but produced greater effects in younger astrocytes. These data indicate effects are related to cellular vitality and not due to accumulation of βA. Support or Funding Information Support: Trinity University Murchison Undergraduate Research Fellowship (EKD), Trinity University Biology Department and Neuroscience Program.