Immunohistochemical study on the distribution of insulin-like growth factor-binding protein 4 in the central nervous system of SOD1 transgenic mice as an in vivo model of amyotrophic lateral sclerosis

In the present study, we used the SOD1^G93A mutant transgenic mice as an in vivo model of amyotrophic lateral sclerosis (ALS) and performed immunohistochemical studies to investigate the changes of insulin-like growth factor-binding protein 4 (IGFBP4) in the central nervous system. Decreased expression of IGFBP4 was obvious in the cerebral cortex, hippocampus, cerebellar cortex and inferior olive of SOD1^G93A transgenic mice. In the cerebral cortex, there was a significant decrease in IGFBP4 immunoreactivity in the pyramidal cells. In the hippocampal formation, IGFBP4 immunoreactivity was also decreased in the pyramidal cells of CA1–3 areas and the granule cells of dentate gyrus. In the cerebellar cortex, IGFBP4 immunoreactivity was prominent in the granular layer in wtSOD1 transgenic mice, compared to that in SOD1^G93A transgenic mice. IGFBP4 immunoreactivity was decreased in the inferior olive of SOD1^G93A transgenic mice. This study, showing decreased IGFBP4 in different brain regions of SOD1^G93A transgenic mice, may provide clues to understanding the differential susceptibility of neural structures in ALS, suggesting a role of IGFBP4 in an abnormality of cognitive and/or motor function in ALS. The mechanisms and functional implications of these decreases require elucidation.