Transcranial magnetic stimulation attenuates cell loss and oxidative damage in the striatum induced in the 3‐nitropropionic model of Huntington's disease

Abstract

An investigation was conducted on the effect of transcranial magnetic field stimulation (TMS) on the free radical production and neuronal cell loss produced by 3-nitropropionic acid in rats. The effects of 3-nitropropionic acid were evaluated by examining the following changes in: the quantity of hydroperoxides and total radical-trapping antioxidant potential (TRAP), lipid peroxidation products, protein carbonyl groups, reduced glutathione (GSH) content, glutathione peroxidase (GSH-Px), catalase and succinate dehydrogenase (SDH) activities; total nitrite and cell death [morphological changes, quantification of neuronal loss and lactate dehydrogenase (LDH) levels]. Our results reveal that 3-nitropropionic acid induces oxidative and nitrosative stress in the striatum, prompts cell loss and also shows that TMS prevents the harmful effects induced by the acid. In conclusion, the results show the ability of TMS to modify neuronal response to 3-nitropropionic acid.

Mitochondrial modulators in experimental Huntington’s disease: reversal of mitochondrial dysfunctions and cognitive deficits

“…ALA þ ALCAR supplementation has shown to exert protection against ROS-induced oxidative stress at the mitochondrial level by reducing carbonyl formation, decreasing mitochondrial DNA deletion, and improving the expression of the respiratory chain components (Aliev et al, 2011). The excessive generation of reactive nitrite species could be a direct effect of 3-NPeinduced oxidative stress, involving the induction of inducible nitric oxide synthase, which is detrimental to cell survival (Tunez et al, 2006). Supplementing ALA þ ALCAR to 3-NPe treated animals significantly reduced the nitrite levels, which are suggested to occur as a result of decreased inducible nitric oxide synthase activity and low levels of inflammatory cytokines (Nagesh Babu et al, 2011).…”

Oxidative Stress in Skin Fibroblasts Cultures of Patients with Huntington’s Disease

“…These authors could not detect catalase activity in 11-week-old animals and in control 35-week old animals, although for 19-week-old animals the catalase activity was 11-fold lower in transgenic mice compared with controls. Tú -nez et al [12] described a reduction in catalase activity in the striatum of rats induced by 3-nitropropionic acid.…”

“…Nitropropionic acid is able to induce oxidative stress in the striatum [11], and triggers a reduction in glutathione content and catalase and glutathione-peroxidase (GPx) activities [12], and an enhancement in superoxide-dismutase (SOD) activity, in striatal nucleus synaptosomes of rats [13]. Intrastriatal injection of the reversible inhibitor of complex II malonate, also induces age-dependent striatal lesions [14].…”

Glutathione redox cycle dysregulation in Huntington’s disease knock-in striatal cells

“…In HD knock-in striatal cells, mitochondrial dysfunction [27][28][29] may be related to increased formation of superoxide (author's unpublished data) and other cellular ROS, as shown in this study. Moreover, in Wistar rats subjected to the mitochondrial complex II inhibitor 3-nitropropionic acid (3-NP), known to mimic some characteristics of HD, higher peroxide formation was detected when compared to untreated rats [30]. Although HD knock-in striatal cells evidence increased ROS generation, they do not exhibit massive cell death and large or visible mHtt aggregates [17], thus mimicking initial HD cytopathological features.…”