metallothionein and Ataxia

Mitochondrial diseases (MD), such as Leigh syndrome (LS), present with severe neurological and muscular phenotypes in patients, but have no known cure and limited treatment options. Based on their neuroprotective effects against other neurodegenerative diseases in vivo and their positive impact as an antioxidant against complex I deficiency in vitro, we investigated the potential protective effect of metallothioneins (MTs) in an Ndufs4 knockout mouse model (with a very similar phenotype to LS) crossed with an Mt1 overexpressing mouse model (TgMt1). Despite subtle reductions in the expression of neuroinflammatory markers GFAP and IBA1 in the vestibular nucleus and hippocampus, we found no improvement in survival, growth, locomotor activity, balance, or motor coordination in the Mt1 overexpressing Ndufs4

Topics: Animals; Ataxia; beta 2-Microglobulin; Biomarkers; Body Weight; Disease Models, Animal; Electron Transport Complex I; Female; Hippocampus; Inflammation; Male; Metabolome; Metallothionein; Mice, Knockout; Mitochondrial Diseases; Motor Activity; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; RNA, Messenger; Survival Analysis

Methylmercury is a toxic pollutant and is generated by microbial methylation of elemental or inorganic mercury in the environment. Previous study found decreased hepatic MDA levels and urinary mercury levels in methylmercury poisoned rats after sodium selenite treatment. This study further found increased mercury levels in serum samples from methylmercury poisoned rats after selenium treatment. By using size exclusion chromatography coupled to inductively coupled plasma mass spectrometry, three Hg- binding protein fractions and two Se-binding protein fractions were identified with the molecular weight of approximately 21, 40, and 75 kDa and of 40 and 75 kDa, respectively. Elevated mercury level in the 75 kDa protein fraction was found binding with both Hg and Se, which may explain the decreased urinary Hg excretion in MeHg poisoned rats after Se treatment. MALDI-TOF-MS analysis of the serum found that the 75 kDa protein fractions were albumin binding with both Hg and Se and the 21 kDa fraction was Hg- binding metallothionein.

Topics: Animals; Ataxia; Behavior, Animal; Cattle; Mercury; Metallothionein; Methylmercury Compounds; Rabbits; Rats; Rats, Sprague-Dawley; Selenium; Serum Albumin, Bovine