The candidate requests 3 years of predoctoral support to get training in the fields of molecular biology, immunology, and neuroscience as they relate to his studies of the interactions between immunologic effectors and the CNS following the induction of a chronic inflammatory response. The long term objective of this research project is to implicate components of the cellular immune response in the disruption of neural function following the induction of a chronic inflammatory response in the central nervous system (CNS). This research is relevant to both mental health and chronic immune-mediated diseases, as it is based on the premise that multiple etiologic factors function through a common pathway to disrupt neural function. The common pathway is the induction of a chronic CNS inflammatory response. The research will characterize axonal areas, neuronal cell number, spinal cord atrophy, and sodium channel distributions following the induction of a chronic CNS inflammatory response in mice deficient in various immunologic effectors.
The first aim addresses the role of the class I- and class II-mediated immune response in the disruption of axons, neurons, and sodium channel distributions, while specific aim two focuses on the cytotoxic T cell effectors: perforin, fas, fas ligand, and IFN-g. Characterization of axons, neurons, and sodium channels will serve as a sensitive marker of CNS disruption. It is hypothesized that mice deficient in immunologic effectors necessary for the induction of neural dysfunction will have preserved axons and spinal cord areas, as well as increased sodium channel densities in the spinal cord white matter. Furthermore, identification of immunologic effectors that are detrimental to neural function during a persistent CNS inflammatory response could lead to possible therapeutic interventions.
