Region-specific alterations in insulin-like growth factor-I receptor in the central nervous system of nNOS knockout mice

Abstract

In the present study, we investigated layer-specific changes in insulin-like growth factor-I (IGF-1) receptor localization in the cerebral cortex, hippocampus and cerebellum of neuronal nitric oxide synthase knockout (nNOS(-/-)) mice using immunohistochemistry. In the cerebral cortex of control mice, moderately stained cells were seen through the layers II-VI in several cortical regions. In nNOS(-/-) mice, there was a significant decrease in IGF-1 receptor immunoreactivity in the same cortical regions. In the hippocampus of control mice, a distinct immunoreactivity pattern was observed in the CA1-3 areas and dentate gyrus. The immunoreactivity for IGF-1 receptor was differentially decreased in each layer in nNOS(-/-) mice. In nNOS(-/-) cerebellum, IGF-1 receptor immunoreactivity was also significantly decreased in each layer of cerebellar cortex and cerebellar nuclei. To clarify whether decreased expression of IGF-1 receptor in nNOS(-/-) mice was specific, the expression of other receptors for IGF-1 was also evaluated. Receptor tyrosine kinase type A (TrkA receptor) and TrkB receptor were differentially decreased in each layer of the hippocampus or cerebellum of nNOS(-/-) mice. Although further studies of functional features of IGF-1 systems in the nNOS((-/-)) mice are required, our first morphological data may provide insights into NO-induced changes in trophic support as well as basic knowledge required for the study of NO-associated neurological diseases. (C) 2004 Elsevier B.V. All rights reserved.