Angela Wynne

B.S. in Biochemistry, SUNY at Binghamton

Thesis Advisor: Jonathan Godbout

E-Mail: wynne.16@osu.edu

Research:

I am investigating the role of fractalkine (FKN) signaling on microglial acivation and age-related increases in neuroinflammation and behavioral deficits. FKN is a chemokine that is highly expressed by neurons in the brain. There is only one known receptor for FKN and it is expressed mainly by microglia in the brain. FKN signaling from neurons to microglia inhibits microglial activation and prevents neuronal death. I have found that mRNA for FKN is decreased in aged mice compared to adults. This indicates that FKN signaling is impaired in aged mice and may contribute to increased susceptibility to neuroinflammation.

I am currently using primary microglial cell cultures from adult and aged mice to test the affects of soluble FKN on isolated microglia. We have found that in adult microglia cultures, soluble FKN reduces the amount of pro-inflammatory cytokines released in the supernatant. These studies need to be finished using aged microglial cultures. I would also like to confirm that FKN protein in the aged brain is also reduced.

I am also using a transgenic model in which the receptor for FKN has been knocked out (FKNR-/-). My data show that these mice have greater and prolonged increases in proinflammatory cytokines and markers of microglial activation in the brain compared to controls after LPS (i.p.) injection. FKNR-/- mice also show prolonged deficits in social exploratory behavior after LPS injection compared to controls. These are interesting results because by knocking out this one signaling pathway the mice exhibit a phenotype that closely mimics that exhibited by aged mice after LPS injection. We would also like to evaluate depressive-like behaviors in FKNR-/- mice (forced swim test and tail suspension test)

Future studies also include intracerbral ventricular injections of soluble FKN before LPS treatment. We believe that this may attenuate inflammation and sickness behaviors.

Awards:

2009 Trainee travel award, PNIRS

Publications:

Henry CJ, Huang Y, Wynne AM, Godbout JP. Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1beta and anti-inflammatory IL-10 cytokines. Brain Behav Immun. 23(3); 309-17.

Henry CJ, Huang Y, Wynne A, Hanke M, Himler J, Bailey MT, Sheridan JF, Godbout JP (2008)Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia. J Neuroinflammation, 5:15.

Fischer, A.J., Ritchey, E.R., Scott, M.A., Wynne, A. (2008) Bullwhip neurons in the retina regulate the size and shape of the eye. Developmental Biology, 317(1):196-212.

Presentations at National Meetings

Angela Wynne, Justin Himler, Christopher Henry, Yan Huang, Phillip Popovich, and Jonathan Godbout. "Impaired Fractalkine regulation of microglial activation contributes to exacerbated neuroinflammation and prolonged sickness behavior following activation of the peripheral innate immune system". IBMR research day, May 2008.