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Effect of microglia cell activation on neuronal cells in coculture
Author(s) -
Sisk Bryan Anthony,
Miller Rebecca Louise,
Sun Grace
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a980-c
Subject(s) - nadph oxidase , microglia , microbiology and biotechnology , oxidative stress , reactive oxygen species , programmed cell death , biology , chemistry , inflammation , immunology , biochemistry , apoptosis
O 2 − is generated in cells and is a precursor for a range of reactive oxygen species. In phagocytes, O 2 − acts as a microbicidal agent for killing invading micro‐organisms. However, uncontrolled O 2 − production in non‐phagocytic cells can cause severe oxidative stress, and results in extensive tissue damage and destruction. Oxidative stress is thought to be the cause of several disease states, such as Parkinson's, Alzheimer's and stroke. One of the sources of O 2 − is the membrane bound enzyme NADPH‐oxidase, which is comprised of a number of subunits and regulated by protein kinases. Activation of NADPH‐oxidase has been implicated in oxidative stress related disease states. In the central nervous system, neurons and glia cells (astrocytes and microglial cells) cohabitate in the same tissue. After insult, glial cells become activated and may have deleterious impact on neurons. However, how activation of glial cells release factors that cause neuronal death is still unknown. Since NADPH oxidase is present in both astrocytes and microglial cells, it is possible that activation of these glia cells upon local insult lead to activation of NADPH‐oxidase and production of O 2 − which induces oxidative stress. Mechanism for these cells to cause neuronal damage is not well studies. In this series of experiments, we will test effects of activated microglial cells (BV‐2) on retinoic acid‐differentiated neuronal cells (SH‐SY5Y) in two co‐culture systems with contact and without contact. Understanding how microglial alter neuronal function will be important towards understanding many neurodegenerative disease processes. (Supported by 1 P01 AG18357)