Open AccessInjury factors and pathological features of toxic milk mice during different disease stages
Author(s) -
Zhou Xiangxue,
Li Xunhua,
Chen Dingbang,
Wu Chao,
Feng Li,
Qin Haolin,
Pu XiaoYong,
Liang Xiuling
Publication year - 2019
Publication title -
brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.915
H-Index - 41
ISSN - 2162-3279
DOI - 10.1002/brb3.1459
Subject(s) - thalamus , myelin , superoxide dismutase , glutathione peroxidase , nitric oxide synthase , endocrinology , myelin basic protein , luxol fast blue stain , medicine , neurofilament , nucleus , chemistry , pathology , oxidative stress , biology , nitric oxide , central nervous system , immunohistochemistry , neuroscience
Objective To evaluate different injury factors and pathological characteristics of the brain at different disease stages in toxic milk (TX) mice, an animal model of Wilson's disease (WD). Methods Thirty TX mice (10 each at 3, 6 and 12 months old) and 30 age‐matched C57 mice were used in this study. Corrected phase (CP) values were determined from susceptibility‐weighted images. Myelin content was determined by measuring inhibition optical density values of Luxol fast blue‐stained sections. Neurofilament protein 68 kDa (NF68), β‐amyloid precursor protein (β‐APP), and myelin basic protein (MBP) levels, as well as copper and iron content, in brain nuclei of the TX mouse were evaluated. Gene amplification ratios for catalase (CAT), GSH peroxidase (GSH‐PX), nitric oxide synthase (NOS), and superoxide dismutase (SOD) in mouse brain were also determined. Results Compared with C57 mice, neuronal cell counts were decreased in 12‐months‐old TX mice ( p = .011). Myelin content was decreased in the lenticular nucleus ( p = .029), thalamus ( p = .030), and brainstem ( p = .034) of 6‐months‐old TX mice; decreases in the corresponding nuclei ( p = .044, .037, and .032, respectively) were also found in 12‐months‐old TX mice. MBP values were lower in the lenticular nucleus and thalamus ( p = .027 and .016, respectively) of 6‐months‐old TX mice and in the corresponding nuclei ( p = .24 and .040) of 12‐months‐old TX mice. NF‐68 values were lower in the lenticular nucleus and thalamus ( p = .034 and .037, respectively) of 6‐months‐old TX mice and in the corresponding nuclei ( p = .006 and .012) of 12‐months‐old TX mice. β‐APP values were higher in the thalamus of 6‐months‐old ( p = .037) and 12‐months‐old ( p = .012) TX mice. Iron content was higher in the lenticular nucleus, thalamus, and cerebellum ( p = .044, .038, and .029, respectively) of 6‐months‐old TX mice and in the corresponding nuclei ( p = .017, .024, and .029) of 12‐months‐old TX mice. The NOS gene amplification multiple was higher ( p = .039), whereas the SOD1 gene amplification multiple was lower ( p = .041) in 12‐months‐old TX mice. There was no correlation between metal content or oxidation index and pathological index. Conclusions The pathological characteristics of the brains of TX mice may differ at different ages. Different pathogenic factors, including copper and iron deposition and abnormal oxidative stress, are present at different stages.