Mild Exercise Differently Affects Proteostasis and Oxidative Stress on Motor Areas During Neurodegeneration: A Comparative Study of Three Treadmill Running Protocols.

Proteostasis and oxidative stress were evaluated in motor cortex and spinal cord of aged Lewis rats exposed to 1 mg/kg/day of rotenone during 4 or 8 weeks, prior or after practicing three protocols of mild treadmill running. Results demonstrated that exercise done after the beginning of neurodegeneration reverted the increased oxidative stress (measured by H2O2 levels and SOD activity), increased neuron strength, and improved proteostasis in motor cortex. Spinal cord was not affected. Treadmill running practiced before neurodegeneration protected cortical motor neurons of the rotenone-exposed rats; but in this case, oxidative stress was not altered, whereas proteasome activity was increased and autophagy decreased. Spinal cord was not protected when exercise was practiced before neurodegeneration. Prolonged treadmill running (10 weeks) increased oxidative stress, autophagy, and proteasome activity, whereas neuron viability was decreased in motor cortex. In spinal cord, this protocol decreased oxidative stress and increased proteasome activity. Major conclusions were that treadmill running practiced before or after the beginning of neurodegeneration may protect motor cortex neurons, whereas prolonged mild running seems to be beneficial for spinal cord.

Effect of swimming training on nerve morphological recovery after compressive injury.

OBJECTIVE: This study aims to investigate morphological alterations caused by partial sciatic nerve ligation (PNL) and the efficacy of a moderate-intensity swimming training as therapeutic strategy for nerve regeneration. METHODS: A number of 30 male adult mice were equally divided in control, 14 days after PNL (PNL 14 days), 42 days after PNL (PNL 42 days), 70 days after PNL (PNL 70 days) and 5-week exercise training after 7 days post-lesion (PNL trained 35 days) groups. PNL trained 35 days group began with a 10-min session for 3 days and this time was gradually increased by 10 min every three sessions until the animals had swum for 50 min per session. Morphoquantitative analysis was carried out to assess nerve regeneration in each group. RESULTS: PNL 14 days group exhibited less degenerating signs than PNL 42 days group, where most post-lesion alterations were visualized. Nerve area and minimum diameter were significantly lower (p < 0.05) than control group. PNL 70 days group showed a greater degree of regenerating fibers and similar morphometric parameters to control group. PNL trained 35 days demonstrated signs of regeneration, reaching control group values in the morphometric analysis. DISCUSSION: PNL promotes great histopathological changes, which became more visible at 42 post-injury days. A natural nerve-regeneration tendency was observed throughout time, as observed in PNL 70 days group; nevertheless, moderate swimming training was found to be a therapeutic resource for nerve regeneration, accelerating such process from a morphoquantitative perspective. ABBREVIATIONS: ANOVA: One-way analysis of variance; BDNF: Brain-derived neurotrophic factor; FGF-2: Fibroblast growth factor 2; GDNF: Glial cell line derived neurotrophic factor; IGF: Insulin-link growth factor; IL-1ß: Interleukin-1ß; NGF: Neural growth factor; PBS: Phosphate-buffered saline; PNL: Partial sciatic nerve ligation.

An Overview of Potential Targets for Treating Amyotrophic Lateral Sclerosis and Huntington's Disease.

Neurodegenerative diseases affect millions of people worldwide. Progressive damage or loss of neurons, neurodegeneration, has severe consequences on the mental and physical health of a patient. Despite all efforts by scientific community, there is currently no cure or manner to slow degeneration progression. We review some treatments that attempt to prevent the progress of some of major neurodegenerative diseases: Amyotrophic Lateral Sclerosis and Huntington's disease.

Neuroprotective effects and magnetic resonance imaging of mesenchymal stem cells labeled with SPION in a rat model of Huntington's disease.

Bone marrow mesenchymal stem cells (MSC) have been tested and proven effective in some neurodegenerative diseases, but their tracking after transplantation may be challenging. Our group has previously demonstrated the feasibility and biosafety of rat MSC labeling with iron oxide superparamagnetic nanoparticles (SPION). In this study, we investigated the therapeutic potential of SPION-labeled MSC in a rat model of Huntington's disease, a genetic degenerative disease with characteristic deletion of striatal GABAergic neurons. MSC labeled with SPION were injected into the striatum 1h after quinolinic acid injection. FJ-C analysis demonstrated that MSC transplantation significantly decreased the number of degenerating neurons in the damaged striatum 7 days after lesion. In this period, MSC transplantation enhanced the striatal expression of FGF-2 but did not affect subventricular zone proliferation, as demonstrated by Ki67 proliferation assay. In addition, MSC transplantation significantly reduced the ventriculomegaly in the lesioned brain. MRI and histological techniques detected the presence of the SPION-labeled cells at the lesion site. SPION-labeled MSC produced magnetic resonance imaging (MRI) signals that were visible for at least 60 days after transplantation. Our data highlight the potential of adult MSC to reduce brain damage under neurodegenerative diseases and indicate the use of nanoparticles in cell tracking, supporting their potential as valuable tools for cell therapy.

Long-term effects of environmental stimulation following hypoxia-ischemia on the oxidative state and BDNF levels in rat hippocampus and frontal cortex.

Environmental enrichment recovers memory deficits without affecting atrophy of the hippocampus adult rats submitted to neonatal hypoxia-ischemia (HI). The present study was designed to investigate whether the modulation of brain oxidative status and/or BDNF content, as assessed in adulthood, are involved with the functional neuroprotection caused by environmental enrichment in animals receiving neonatal HI. Male Wistar rats, in the 7th postnatal day, were submitted to the Levine-Rice model of neonatal hypoxia-ischemia, comprising permanent occlusion of the right common carotid artery and a 90 min period of hypoxia (8% O(2)-92% N(2)). Starting 2 weeks after the HI event, animals were stimulated by the enriched environment (1 h/day for 9 weeks). Rats were sacrificed approximately 24 h after the end of enrichment period and some oxidative stress parameters, specifically the free radical levels, macromolecules damage and superoxide dismutase activity, in hippocampus and frontal cortex samples were determined. BDNF levels were also measured in the same encephalic structures. Indexes of macromolecules damage, TBARS levels and total cellular thiols, as well as free radical levels were unchanged in both studied structures. An increased SOD activity in the right hippocampus of HI group maintained in standard environment was found, this effect was reversed in HI enriched group. Moreover, BDNF levels were increased only in the hippocampus of non-stimulated HI group. These results suggest that the environmental enrichment protocol bearing cognitive protection is not associated to increases in BDNF expression nor SOD activity in hippocampus of the rats, as assessed in adulthood, submitted to neonatal hypoxia-ischemia.

Exercise intensity influences cell injury in rat hippocampal slices exposed to oxygen and glucose deprivation.

We evaluated the effects of two levels of daily forced exercise intensity (moderate and high) in the treadmill over cell susceptibility to oxygen and glucose deprivation (OGD) in hippocampal slices from Wistar rats. Moderate exercise decreased lactate dehydrogenase (LDH) release after OGD, while a significant increase in LDH release was observed in the high intensity group submitted to OGD. Our data corroborate the hypothesis that higher training intensity exacerbates brain damage, while a moderate intensity reduces the injury caused by in vitro ischemia.