title: Essential roles of mitochondrial depolarization in neuron loss through microglial activation and attraction toward neurons.
abstract: As life spans increased, neurodegenerative disorders that affect aging populations have also increased. Progressive neuronal loss in specific brain regions is the most common cause of neurodegenerative disease; however, key determinants mediating neuron loss are not fully understood. Using a model of mitochondrial membrane potential (ΔΨm) loss, we found only 25% cell loss in SH-SY5Y (SH) neuronal mono-cultures, but interestingly, 85% neuronal loss occurred when neurons were co-cultured with BV2 microglia. SH neurons overexpressing uncoupling protein 2 exhibited an increase in neuron-microglia interactions, which represent an early step in microglial phagocytosis of neurons. This result indicates that ΔΨm loss in SH neurons is an important contributor to recruitment of BV2 microglia. Notably, we show that ΔΨm loss in BV2 microglia plays a crucial role in microglial activation and phagocytosis of damaged SH neurons. Thus, our study demonstrates that ΔΨm loss in both neurons and microglia is a critical determinant of neuron loss. These findings also offer new insights into neuroimmunological and bioenergetical aspects of neurodegenerative disease.
authors: Department of Biomedical Sciences, College of Medicine, the Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors: Min-Kyung
authors: MK
authors: Nam
authors: Hyun-Ah
authors: HA
authors: Shin
authors: Ji-Hye
authors: JH
authors: Han
authors: Dae-Wook
authors: DW
authors: Park
authors: Hyangshuk
authors: H
authors: Rhim
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D057899:Cytophagocytosis / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D039823:Iridoids / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D011134:Polysaccharides / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D061209:Proton Ionophores / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000235:genetics; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D004298:Dopamine; D049452:Green Fluorescent Proteins; D000074923:High-Temperature Requirement A Serine Peptidase 2; D007376:Interleukin-2; D039823:Iridoids; D007770:L-Lactate Dehydrogenase; D024101:Mitochondrial Proteins; D011134:Polysaccharides; D011518:Proto-Oncogene Proteins; D061209:Proton Ionophores; D012697:Serine Endopeptidases; D015534:Trans-Activators; D014404:Tubulin; D000099232:Proto-Oncogene Protein Spi-1; C462941:beta3 tubulin, mouse; C007834:genipin