{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T14:08:35Z","timestamp":1765807715078,"version":"3.41.2"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty TX mice (10 each at 3, 6 and 12\u00a0months old) and 30 age\u2010matched C57 mice were used in this study. Corrected phase (CP) values were determined from susceptibility\u2010weighted images. Myelin content was determined by measuring inhibition optical density values of Luxol fast blue\u2010stained sections. Neurofilament protein 68\u00a0kDa (NF68), \u03b2\u2010amyloid precursor protein (\u03b2\u2010APP), 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\u2010PX), nitric oxide synthase (NOS), and superoxide dismutase (SOD) in mouse brain were also determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with C57 mice, neuronal cell counts were decreased in 12\u2010months\u2010old TX mice (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.011). Myelin content was decreased in the lenticular nucleus (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.029), thalamus (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.030), and brainstem (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.034) of 6\u2010months\u2010old TX mice; decreases in the corresponding nuclei (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.044, .037, and .032, respectively) were also found in 12\u2010months\u2010old TX mice. MBP values were lower in the lenticular nucleus and thalamus (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.027 and .016, respectively) of 6\u2010months\u2010old TX mice and in the corresponding nuclei (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.24 and .040) of 12\u2010months\u2010old TX mice. NF\u201068 values were lower in the lenticular nucleus and thalamus (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.034 and .037, respectively) of 6\u2010months\u2010old TX mice and in the corresponding nuclei (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.006 and .012) of 12\u2010months\u2010old TX mice. \u03b2\u2010APP values were higher in the thalamus of 6\u2010months\u2010old (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.037) and 12\u2010months\u2010old (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.012) TX mice. Iron content was higher in the lenticular nucleus, thalamus, and cerebellum (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.044, .038, and .029, respectively) of 6\u2010months\u2010old TX mice and in the corresponding nuclei (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.017, .024, and .029) of 12\u2010months\u2010old TX mice. The NOS gene amplification multiple was higher (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.039), whereas the SOD1 gene amplification multiple was lower (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.041) in 12\u2010months\u2010old TX mice. There was no correlation between metal content or oxidation index and pathological index.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.1459","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T17:58:30Z","timestamp":1574186310000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Injury factors and pathological features of toxic milk mice during different disease stages"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6583-9734","authenticated-orcid":false,"given":"Xiang\u2010xue","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Neurology The East Area of the First Affiliated Hospital Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xun\u2010hua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of 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Hospital Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Yong","family":"Pu","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine and Urology Guangdong General Hospital Guangdong Academy of Medical Sciences Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiu\u2010ling","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital Sun Yat\u2010Sen University Guangzhou 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