Increased oxidative damage and mitochondrial abnormalities in the peripheral blood of Huntington’s disease patients

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Abstract

Increased oxidative stress and mitochondrial abnormalities contribute to neuronal dysfunction in Huntington’s disease (HD). We investigated whether these pathological changes in HD brains may also be present in peripheral tissues. Leukocyte 8-hydroxydeoxyguanosine (8-OHdG) and plasma malondialdehyde (MDA) were elevated, and activities of erythrocyte Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and glutathione peroxidase (GPx) reduced in 16 HD patients when compared to 36 age- and gender-matched controls. Deleted and total mitochondrial DNA (mtDNA) copy numbers were increased, whereas the mRNA expression levels of mtDNA-encoded mitochondrial enzymes are not elevated in HD leukocytes compared to the normal controls. Plasma MDA levels also significantly correlated with HD disease severity. These results indicate means to suppress oxidative damage or to restore mitochondrial functions may be beneficial to HD patients. Plasma MDA may be used as a potential biomarker to test treatment efficacy in the future, if confirmed in a larger, longitudinal study.

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Materials and methods

Subjects. Sixteen genetically confirmed HD patients and 36 age- and gender-matched healthy controls without any neurological disease were studied with care to avoid differences in confounding factors known to influence oxidative stress markers between HD and controls (Table 1). The Unified Huntington’s Disease Rating Scale (UHDRS) [20] were recorded for each patient. All of the subjects gave informed consent for the study.

Blood sample collection and preparation of leukocyte DNA and RNA. Blood

Clinical characteristics of HD patients

The clinical characteristics of the HD patients and controls are displayed in Table 1. There were no significant differences in age, gender, proportions of diabetes mellitus, hypertension, hyperlipidemia, smoking, and use of antioxidant between the HD (n = 16) and control groups (n = 36). The HD patients were divided into two disease severity groups according to their independence scales of UHDRS. Patients with scales ⩽70 represent the more severe group (HD1 group, n = 8). Patients with scales

Discussion

Impaired metabolism, mitochondrial abnormalities, and oxidative stress have been demonstrated in brain tissue for human and rodent models of HD [10], [11], [12], [13], [14], [15], [16]. Although, impaired metabolism and mitochondrial abnormalities have also been found in peripheral tissues [9], [17], [18], [19], direct evidence of increased oxidative stress and decreased anti-oxidant capacity was rarely shown in peripheral blood of HD patients [26].

A significant increase in 8-OHdG in HD caudate

Acknowledgments

This work was supported by Grants 23-4a and 23-5b from Academia Sinica, Taiwan, and CMRPG 32087 from Chang Gung Memorial Hospital, Taipei, Taiwan.

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