This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Lyme neuroborreliosis (LNB) manifests in 10-15% of Lyme disease patients that go untreated. We hypothesized that the Lyme disease spirochete Borrelia burgdorferi (Bb) induces inflammatory mediators in glial cells that contribute to glial and neuronal damage, resulting in the pathogenesis of LNB. Here we evaluate the role of inflammation in mediating apoptosis of oligodendrocytes (OLGs), the myelin producing glial cells in the brain, as induced by Bb, by using the anti-inflammatory drug dexamethasone. We evaluated the potential of live Bb to elicit inflammatory mediators in in vitro differentiated cultures of human MO3.13 OLGs by measuring the levels of immune mediators in culture supernatants using Multiplex ELISA assays. Concomitant apoptosis was quantified in these cultures by the in situ TUNEL assay. The above phenomena were evaluated after 48 hours of stimulation with Bb in the presence and absence of various concentrations of the anti-inflammatory drug dexamethasone. Bb induced significantly enhanced levels of the cytokine IL-6 and the chemokines IL-8 and CCL2 (MCP-1) as compared to basal levels in OLGs. These Bb-induced cultures also showed significantly elevated levels of apoptosis as compared to medium controls. Bb induced inflammatory mediators and apoptosis in OLGs in a dose dependent manner. Dexamethasone significantly reduced both the levels of immune mediators as well as apoptosis as induced by Bb when used at lower concentrations (5 and 15 micro molar). Dexamethasone modulates the levels of inflammatory mediators and concomitant apoptosis induced by the Lyme disease spirochete Bb in OLGs, suggesting that the inflammatory response elicited in OLGs by Bb contributes to their apoptotic cell death. As OLGs are vital for the functioning and survival of neurons, the inflammation and subsequent apoptosis of OLGs induced by Bb could contribute to the pathogenesis of LNB.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-50
Application #
8358082
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
50
Fiscal Year
2011
Total Cost
$37,186
Indirect Cost
Name
Tulane University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
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