Abstract
Mitochondrial dysfunction has been shown to be associated with normal ageing and may account for age-related vulnerability to disease. The increasing number of old people worldwide has created the need to find effective therapeutic agents to reduce the incidence of age-related disease. In the current report, we carried out an assessment of mitochondrial function in established young, middle-aged and old synaptosomal mitochondria bearing cybrids without or with melatonin treatment. The cybrids were generated by transferring isolated mitochondria from synaptosomes of brain cortical cells in mice to rho-zero mtDNA-less cells. In galactose media, a selective media that tests a cells ability to produce ATP through the electron transport chain and oxidative phosphorylation, 500μM melatonin (N-acetyl-5-methoxytryptamine) raised cell viability in young and middle-aged cybrids (P < 0.05) and a concentration of 1mM raised cell viability in the old cybrids (P < 0.05). The mitochondrial membrane potential (MMP) was lowered in the young cybrids (P < 0.05) treated with melatonin, but it was raised in the middle-aged and old cybrids (P < 0.05) with melatonin treatment. The levels of reactive oxygen species were significantly lower in the melatonin treated middle-aged and old cybrids compared with controls (P < 0.05). Furthermore, ATP measurements showed no significant increase in the young cybrids (P > 0.05), but increased significantly in the middle-aged and old cybrids (P < 0.05) with melatonin treatment. Light and fluorescence microscopy showed observable structural damage and cell death in the middle-aged and old cybrids without melatonin treatment. The results suggest that melatonin may be a potent therapeutic intervention during age-related neuronal mitochondrial dysfunction.
Original language | English (US) |
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Pages (from-to) | 145-152 |
Number of pages | 8 |
Journal | Nigerian Journal of Physiological Sciences |
Volume | 32 |
Issue number | 2 |
State | Published - 2017 |
Keywords
- Ageing
- Melatonin
- Neuronal mitochondria
- Synaptosomes
ASJC Scopus subject areas
- Physiology
- Physiology (medical)