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179 OVEREXPRESSION OF THE 5HT3 RECEPTOR AND PRODUCTION OF LIPOPOLYSACCHARIDE-INDUCED INTERLEUKIN-1BETA CYTOKINE.
  1. D. Fitzsimmons-Pattison,
  2. D. Chabot-Richards,
  3. A. Allan
  1. Department of Neuroscience, University of New Mexico School of Medicine, Albuquerque, NM

Abstract

Neurogenesis, the growth of new neural cells, occurs primarily in the hippocampus and can be seen throughout the life span. Proper progression of neurogenic processes have been linked to protection from depression and improved learning and memory. The 5-HT3 overexpressing (5HT3-OE) mouse model has been demonstrated to have reduced stress, reduced learned helpless behavior (a measure of depression), and improved performance in fear-conditioned learning tasks. More recently, these mice have been shown to have increased survival of new neurons compared to their wild-type counterparts. Changes in neurogenesis are followed using a series of daily injections of a compound, 5 bromo2′deoxyuridine (BrdU). Most often, BrdU is prepared in a standard saline solution that has not been specifically treated to eliminate lipopolysaccharides (LPS). Lipopolysaccharides are known to be present in most water sources and multiple injections of solutions containing LPS could induce peripheral inflammatory state, which might impact neurogenesis and the fate of new neuronal cells. In this study we compared the effect of BrdU prepared in standard saline with that of LPS-free saline on the production of the inflammatory cytokine, IL-1β (interleukin 1beta) in the plasma from 5-HT3 overexpressing mice and their wild-type counterparts. A 7-day regimen of BrdU injection with the standard solutions produced a significant increase in IL-1β in the plasma from wild-type mice compared to plasma taken from the wild-type mice injected with the LPS-free BrdU solutions. Overexpression of the 5HT3 receptor appeared to protect mice from the injection mediated increase in IL-1β. These findings suggest that the 5HT3-OE mice may have a natural resistance to infection and may suggest a mechanism for the increased neuronal survival seen in these mice. Further, these studies highlight the importance of using LPS-free solutions when multiple injection regimens are planned.

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