Immunohistochemical study on the distribution of homocysteine in the central nervous system of transgenic mice expressing a human Cu/Zn SOD mutation

In the present study, we used the transgenic mice expressing a human Cu/Zn SOD mutation (SOD1^G93A) as an in vivo model of ALS and performed immunohistochemical studies to investigate the changes of homocysteine in the central nervous system of symptomatic transgenic mice. In control and presymptomatic transgenic mice, homocysteine-immunoreactive astrocytes were not detected in any region. In symptomatic transgenic mice, homocysteine-immunoreactive astrocytes were distributed in the spinal cord, brainstem and cerebellar nuclei of transgenic mice. In the hippocampal formation of transgenic mice, pyramidal cells in the CA1-3 regions and granule cells in the dentate gyrus showed homocysteine immunoreactivity. The present study provides the first in vivo evidence that homocysteine immunoreactive astrocytes were found in the central nervous system of symptomatic SOD^G93A transgenic mice, suggesting that reactive astrocytes may play an important role in the pathogenesis and progress of ALS. This study also suggests that increased expression of homocysteine in the hippocampal neurons might reflect a role of homocysteine in an abnormality of hippocampal function of ALS.