Immunocytochemical study on the distribution of nitrotyrosine in the brain of the transgenic mice expressing a human Cu/Zn SOD mutation.

Abstract:

:In the previous study, we reported increased NOS expression in the astrocytes in the spinal cord of the transgenic mice that are used as ALS animal model. In the present study, we performed immunocytochemical studies to investigate the changes of nitrotyrosine-immunoreactivity in the brains of the transgenic mice, and demonstrated in vivo evidence of peroxynitrite-mediated oxidative damage in the pathogenesis of ALS. In the spinal cord of the transgenic mice, immunocytochemistry showed intensely stained nitrotyrosine-IR glial cells with the appearance of astrocytes, but no nitrotyrosine-IR glial cells were observed in the spinal cord of the control mice. In the transgenic mice, nitrotyrosine-IR neurons were observed in the hypoglossal nucleus, lateral reticular nucleus, medullary reticular formation and cerebellar nuclei. Interestingly, nitrotyrosine-IR neurons were observed in the hippocampal formation and septal area of the transgenic mice. In the hippocampus, nitrotyrosine-IR neurons in the CA1 region showed intense staining, and the immunoreactivity was localized mainly in the pyramidal cell layer. Recent studies have shown that antioxidants and selective neuronal NOS inhibitor increase survival in the SOD1 transgenic mouse model of FALS. It is possible that therapy with these agents may slow the neurodegenerative process in human ALS, perhaps through reduction of nitrotyrosine formation.

journal_name

Brain Res

journal_title

Brain research

authors

Cha CI,Chung YH,Shin CM,Shin DH,Kim YS,Gurney ME,Lee KW

doi

10.1016/s0006-8993(99)02302-1

subject

Has Abstract

pub_date

2000-01-17 00:00:00

pages

156-61

issue

1

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(99)02302-1

journal_volume

853

pub_type

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