IL-1 Beta influences on NGF in neural Development

Western Michigan University, Kalamazoo MI

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Abstract

DESCRIPTION (provided by applicant): An intriguing problem in developmental neurobiology is how cytokines and growth factors interact to shape the differentiation, survival or plasticity of specific neural circuits during development. The cytokine, interleukin-1beta is expressed in the developing nervous system, independent of neuroimmune or neuroendocrine function, indicating that it may play an important role in neural development. However, its role is not yet completely understood. In mammalian glial cells, IL-1beta induces the neurotrophin, nerve growth factor (NGF), through an NF-KB mediated signal transduction mechanism during neural development. My previous work in the developing frog, has shown that IL-1beta and the interleukin-1 type I receptor (IL-1RI) are expressed in identifiable neurons and other neural cell types that comprise functional, sensory motor locomotor circuits. Pilot studies demonstrated that the interleukin-1 receptor antagonist protein (IL-1ra) and NGF are co-expressed with IL-1beta and IL-1RI. The work in this proposal tests the idea that IL-1beta regulates NGF expression in developing neural circuits of the frog, Xenopus laevis, through an NF-KB signal transduction mechanism. The proposed work will complete pilot studies defining IL-1ra and NGF protein expression in developing neural circuits. Additional experiments will inhibit neural IL-1beta by microinjection of IL-1ra or by exposure to the environmental contaminant, methyl mercury. The effects of IL-1beta inhibition on IL-1beta, XrelA (NF-KB homolog) and NGF gene expression will be analyzed using real-time PCR. This work will establish a system for understanding how cytokines and neurotrophins interact during neural development to influence the development and/or maintenance of functional neural circuits.