Enhanced expression of erythropoietin in the central nervous system of SOD1(G93A) transgenic mice

Abstract

In the present study, we investigated the changes of erythropoietin (Epo) expression in the central nervous system (CNS) of SOD1(G93A) transgenic mice as an in vivo model of amyotrophic lateral sclerosis (ALS). In wild-type SOD1 (wtSOD1) transgenic mice, little immunoreactivity was found in all cortical regions. In the cerebral cortex of symptomatic SOD1(G93A) transgenic mice, there was a significant increase in Epo immunoreactivity. In the hippocampal formation, layer-specific alterations in the staining intensity were observed in the CA1-3 areas and dentate gyrus. Epo immunoreactivity was significantly increased in the midbrain, cerebellar cortex and brainstem of SOD1(G93A) transgenic mice. On the contrary, Epo immunoreactivity was moderately stained in the spinal cord and was not different between wtSOD1 and SOD1(G93A) transgenic mice at the age of 8 weeks, 13 weeks and 18 weeks. In the staining of Epo receptor (EpoR), the changing pattern was similar with that of Epo in the spinal cord and hippocampal formation in wtSOD1 and SOD1(G93A) transgenic mice. Although further studies of functional features of Epo in ALS are needed, the first demonstration of increased immunoreactivity for Epo in the CNS of SOD1(G93A) transgenic mice may provide initial insights into the development of interventional strategies to alleviate motor neuron degeneration in human ALS. (C) 2004 Elsevier B.V. All rights reserved.