Multiple system atrophy in a patient with primary ciliary dyskinesia

We present the case of a patient with primary ciliary dyskinesia who later developed clinically probable multiple system atrophy. Multiple system atrophy is a sporadic neurodegenerative disorder clinically characterised by various combinations of parkinsonism, cerebellar ataxia, autonomic failure, and pyramidal sign. Primary ciliary dyskinesia is a genetically heterogeneous disorder of motile cilia and results in chronic bronchitis, bronchiectasis, chronic rhinosinusitis, chronic otitis media, situs inversus, and male infertility. Most of the causative genes for primary ciliary dyskinesia encode proteins that are part of the heavy or intermediate chain of axonemal dynein in ciliary outer dynein arms. We hypothesised that axonemal dynein dysfunction in primary ciliary dyskinesia results in reduced autophagy, accompanied by impaired cytoplasmic dynein function, which in turn accelerates -synucleinopathy in multiple system atrophy. Furthermore, we contemplated a potential association between primary cilia and neuronal function. Although it is not yet clear if a causal link between multiple system atrophy and primary ciliary dyskinesia exists, further investigation into the relationship between axonemal dynein dysfunction in primary ciliary dyskinesia and α-synucleinopathy should be conducted.

Inhibitory effect of α-tocopherol on methylmercury-induced oxidative steress

<p><b>OBJECTIVES</b>The present study investigated the involvement of oxidative stress in the degeneration of the cerebellum during methylmercury (MeHg) intoxication and the protective effect of α-tocopherol (Vit E) against MeHg toxicity.</p><p><b>METHODS</b>After 5 mg/kg of MeHg was administered to Wistar rats for 12 consecutive days, the cerebellum were examined histopathologically. In addition, the same amount of MeHg was administered to 3 different groups of Wistar rats: rats with a Vit E-deficient diet, rats fed 150 mg/kg of Vit E for 20 consecutive days after initial MeHg administration, and rats with an ordinary diet.</p><p><b>RESULTS</b>Positive immunoreactivity against anti-hydroxynonenal (HNE), a marker of lipid peroxidation, was observed in the cerebellum after MeHg administration. Levels of thiobarbituric acid reactive substance (TBARS), another marker of lipid peroxidation, and those of protein carbonyl, a biomarker for protein oxidation, increased after MeHg administration. In the rats with MeHg and a Vit E-deficient diet, mortality and prevalence of piloerection significantly increased, and in the rats with MeHg and Vit E, mortality, piloerection, retracted and crossed hind leg, and ataxic gait significantly decreased, compared with the rats with MeHg alone. The levels of NO(2) (-) and NO(3) (-) in the serum significantly increased in the rats with MeHg alone 14 days after the initial MeHg administration, but were significantly suppressed by Vit E administration.</p><p><b>CONCLUSIONS</b>Oxidative stress, especially lipid peroxidation, may play an important role in the cerebellar degeneration process during MeHg intoxication and Vit E may play a protective role against MeHg toxicity as an effective antioxidant.</p>

Inhibitory Effect of $\alpha$-Tocopherol on Methylmercury-Induced Oxidative Steress

Objectives: The present study investigated the involvement of oxidative stress in the degeneration of the cerebellum during methylmercury (MeHg) intoxication and the protective effect of α-tocopherol (Vit E) against MeHg toxicity. Methods: After 5 mg/kg of MeHg was administered to Wistar rats for 12 consecutive days, the cerebellum were examined histopathologically. In addition, the same amount of MeHg was administered to 3 different groups of Wistar rats: rats with a Vit E-deficient diet, rats fed 150 mg/kg of Vit E for 20 consecutive days after initial MeHg administration, and rats with an ordinary diet. Results: Positive immunoreactivity against anti-hydroxynonenal (HNE), a marker of lipid peroxidation, was observed in the cerebellum after MeHg administration. Levels of thiobarbituric acid reactive substance (TBARS), another marker of lipid peroxidation, and those of protein carbonyl, a biomarker for protein oxidation, increased after MeHg administration. In the rats with MeHg and a Vit E-deficient diet, mortality and prevalence of piloerection significantly increased, and in the rats with MeHg and Vit E, mortality, piloerection, retracted and crossed hind leg, and ataxic gait significantly decreased, compared with the rats with MeHg alone. The levels of NO2− and NO3− in the serum significantly increased in the rats with MeHg alone 14 days after the initial MeHg administration, but were significantly suppressed by Vit E administration. Conclusions: Oxidative stress, especially lipid peroxidation, may play an important role in the cerebellar degeneration process during MeHg intoxication and Vit E may play a protective role against MeHg toxicity as an effective antioxidant.