Towards an Understanding of Integrative Brain Functions

Transgenic mice and cytokine actions in the brain: bridging the gap between structural and functional neuropathology

Iain L. Campbell*
Department of Neuropharmacology, CVN 9, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA

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Abstract
Deciphering the neurobiological consequences of cerebral cytokine expression in vivo respresents an important research objective which has implications for our understanding of the pathogenesis and treatment of many significant neurological disorders. In our own pursuit of this objective, studies by us have utilized a transgenic strategy employing the GFAP promoter to direct the chronic expression of the cytokines IL-3, IL-6, IFN-a or TNF-a to astrocytes in mice. Transgenic expression of each cytokine produces a unique spectrum of neuropathological and functional alterations, thereby directly implicating these mediators in the pathogenesis of CNS disease. Moreover, as exemplified here with the GFAP-IL6 transgenic mice, these models are valuable tools in which to perform multi-level analysis to link molecular and cellular alterations to specific electrophysical, neuroendocrine and behavioral outcomes. Integrative studies such as described here in the GFAP-cytokine transgenic mice, are providing a more thorough understanding of the actions of cytokines in the CNS and bridge the gap between structural and functional neuropathology.

Corresponding author: icamp@scripps.edu

Brain Research Reviews 26 (1998) 327-336
Copyright © 1998 Elsevier Science B. V. All rights reserved.