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UNIVERSITY OF ILLINOIS AT CHICAGO Department of Psychiatry Fifth Annual Research Forum – Extravaganza 2014 POSTER TITLE Increased Toll-like receptor 2 and 6 protein expression the depressed suicide brain DISEASE/KEY WORDS: TLR2, TLR5, TLR6, depression, suicide, postmortem brain AUTHORS: Xinguo Ren, M.D., Hooriyah S. Rizavi, M.S., Ghanshyam N. Pandey, Ph. D MENTEE CATEGORY: RESEARCH MENTOR: Ghanshyam N. Pandey, Ph. D. BACKGROUND: Abnormalities of the immune function in depression and suicide are based in part on the observation of increased levels of proinflammatory cytokines in the serum and in postmortem brain of depressed and suicidal patients. Several studies suggest dysregulation of the immune system in suicide as increased microgliosis has been reported in postmortem brain of suicide subjects and increased levels of proinflammatory cytokines in the CSF of suicidal patients. This observed abnormality of cytokines in suicide may be related to altered innate immune receptors known as Toll-like receptors (TLRs). In a recent study we reported a significant increase in the protein and mRNA levels of TLR3 and TLR4. To further examine the role of TLR in suicide we have now studied the expression of TLR2, TLR5, and TLR6 in depressed suicide subjects. METHODS: We determined the protein expression of TLR2, TLR5, and TLR6 in the PFC of 24 depressed suicide victim and 24 normal control subjects. The postmortem brain tissues were obtained from the Maryland Brain Collection and the psychological autopsies were performed for the diagnosis of the subjects using DSM-IV-SCID. Protein expression was determined using Western blot technique. RESULTS: When we compared the protein expression of TLR2, TLR5 and TLR6 of adult suicide brain with the normal control subjects, we found UNIVERSITY OF ILLINOIS AT CHICAGO Department of Psychiatry that the protein expression of TLR2 was significantly increased in depressed suicide victims compared with normal control subjects, while there was no difference in TLR5 protein expression in depressed suicide victims compared with normal control subjects. The protein expression of TLR6 was also significantly increased in the PFC of depressed suicide subjects compared with normal controls. CONCLUSIONS: These results suggest that overexpression of TLR2 and TLR6 protein may be in part related to the abnormalities of proinflammatory cytokines in the brain of suicide victims and that abnormalities of innate immunity are associated with suicide.