The function of microglia, either neuroprotection or neurotoxicity, is determined by the equilibrium among factors released from activated microglia in vitro.
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.
Li
Lv
L
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, MD10, 4 Medical Drive, Singapore 117597, Singapore.
Lu
Jia
J
Tay
Samuel Sam Wah
SS
Moochhala
Shabbir M
SM
He
Bei Ping
BP
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
D017304:Annexin A5; D017077:Culture Media, Conditioned; D016207:Cytokines; D006018:Glycols; D008070:Lipopolysaccharides; C007938:2,5-hexanediol