Differential effects of melatonin on amyloid-beta peptide 25-35-induced mitochondrial dysfunction in hippocampal neurons at different stages of culture.
beta-Amyloid (Abeta) is strongly involved in the pathogenesis of Alzheimer's disease (AD), and mitochondria play an important role in neurodegenerative disorders. To determine whether any different effect of melatonin on cultured neurons treated with Abeta in vitro and which may be produced through its different action on mitochondria at different stages of culture, we investigated the damage of cultured rat hippocampal neurons mitochondrial function induced by Abeta in young neurons [days in vitro 10 (DIV 10)] and senescent neurons (DIV 25) and the protective effect of melatonin. Rat hippocampal neurons were incubated with amyloid-beta peptide 25-35 (Abeta25-35) alone or pretreatment with melatonin. Cell viability, mitochondrial membrane potential (Deltapsim), ATP and the activity of the respiratory chain complexes were measured. Data showed that Abeta25-35 caused a reduction in Deltapsim, inhibited the activity of the respiratory chain complexes and led to ATP depletion, melatonin attenuated Abeta25-35-induced mitochondrial impairment in young neurons, whereas melatonin had no effect on Abeta25-35-induced mitochondrial damage in senescent neurons. These results demonstrate that melatonin has differential effect on Abeta25-35-induced mitochondrial dysfunction at different stages of culture and suggest that melatonin is useful for the prevention of AD, rather than treatment.
Dong
Weiguo
W
Department of Oral Anatomy and Physiology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, China.
Huang
Fang
F
Fan
Wenguo
W
Cheng
Shaowu
S
Chen
Yue
Y
Zhang
Wenguang
W
Shi
Hong
H
He
Hongwen
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000544:Alzheimer Disease / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D000255:Adenosine Triphosphate; D008550:Melatonin