title: The function of microglia, either neuroprotection or neurotoxicity, is determined by the equilibrium among factors released from activated microglia in vitro.
abstract: Opposing functions of activated microglia, namely neuroprotection or neurotrophy versus neurodestruction or neurotoxicity, have been observed in a number of experimental models of neurotrauma and neurodegenerative diseases. However, the mechanism(s) involved in the determination of which function activated microglia execute under a given set of conditions still remains to be elucidated. Our current in vitro study has revealed that a neuroprotective/neurotrophic or a neurodestructive/neurotoxic microglial function may be configured by the equilibrium among various microglial factors released into the microenvironment. When NSC-34 neurons were treated with lower concentrations of lipopolysaccharide-stimulated BV-2 microglial conditioned medium (LPS-BVCM), viability of the NSC-34 neurons increased, outgrowth of neuronal processes was promoted, and the formation of 2,5-hexanedione-induced aggregates was prevented. However, when NSC-34 neurons were treated with higher concentrations of the same LPS-BVCM, neuronal viability was reduced, apoptosis was induced and outgrowth of neuronal processes was prevented. Measurement of the cytokines tumor necrotic factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in the LPS-BVCM has shown that the upregulation in expression for each cytokine varied both temporally and quantitatively. It is postulated that an alteration in the concentration of the LPS-BVCM might significantly affect the functional balance of microglial factors in the microenvironment with a resultant different microglial function.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, MD10, 4 Medical Drive, Singapore 117597, Singapore.
authors.forename: Lv
authors.initials: L
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Lu
authors.forename: Samuel Sam Wah
authors.initials: SS
authors.lastname: Tay
authors.forename: Shabbir M
authors.initials: SM
authors.lastname: Moochhala
authors.forename: Bei Ping
authors.initials: BP
authors.lastname: He
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D049108:Cell Enlargement; D048708:Cell Growth Processes / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006018:Glycols / Q000494:pharmacology; D006825:Hybridomas; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: D017304:Annexin A5; D017077:Culture Media, Conditioned; D016207:Cytokines; D006018:Glycols; D008070:Lipopolysaccharides; C007938:2,5-hexanediol