Neuroscience
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Stroke is a leading cause of death and disability in industrialized countries. Although surviving patients exhibit a certain degree of restoration of function attributable to brain plasticity, the majority of stroke survivors has to struggle with persisting deficits. In order to potentiate post-stroke recovery, several rehabilitation therapies have been undertaken and many experimental studies have reported that brain-derived neurotrophic factor (BDNF) is central to many facets of neuroplastic processes. ⋯ In both hippocampal territories, the pattern of mature BDNF expression shows a more delayed increase (from 8 to 30d), which coincides with the evolution of synaptophysin expression. Interestingly, in these hippocampal territories, pro-BDNF levels evolve differently suggesting a differential gene regulation between the two hemispheres. While highlighting the complexity of changes in BDNF metabolism after stroke, our data suggest that BDNF involvement in spontaneous post-stroke plasticity is region-dependent.
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Involvement of Nrf2 signaling pathway in the neuroprotective activity of natural kaurane diterpenes.
Oxidative stress is a common harmful condition of several neurodegenerative diseases. Antioxidants represent the medical choice strategy for protection against this unbalanced oxidant-antioxidant status. The present study was undertaken to address the role of kaurane diterpenes foliol, linearol and sidol in the protection against H(2)O(2)-induced oxidative stress in the human astrocytoma U373-MG cell line and to establish the underlying mechanisms. ⋯ Furthermore, these natural products increased Nrf2 nuclear levels, suggesting the activation of this master regulator of antioxidative gene expressions in the protective effect exhibited by the kaurane diterpenes studied. Collectively, these results suggest that the studied kaurane diterpenes, mainly linearol and sidol, protect U373-MG cells from H(2)O(2)-induced injury or degeneration presumably by antioxidant mechanisms. These compounds may be useful agents for counteracting the oxidative damage occurring during the pathological development of several CNS disorders.
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Fibronectin type III domain-containing 5 protein (Fndc5) or peroxisomal protein, is a type I membrane protein that has 209 amino acid residues. Previous studies by our group have shown an increase in its expression after retinoic acid treatment of mouse embryonic stem cells (mESCs) during the process of neural differentiation, leading us to conclude that it might be involved in neurogenesis. In the present study, we have constructed an inducible short hairpin RNA (shRNA) vector that is expressed under induction by doxycycline. ⋯ Fndc5 knockdown during both stages significantly affected both neuronal and astrocytes maturation. We have concluded that Fndc5 expression is required for the appropriate neural differentiation of mESCs. These data confirm the importance of Fndc5 in the generation and development of the nervous system.
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Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitors administered prior to or immediately after experimental stroke confer acute neuroprotection. However, it remains unclear if delayed treatment with a PTEN inhibitor improves long-term functional recovery after stroke. We addressed the issue in this study. ⋯ Akt and mTOR activation are the well-established cascades downstream to PTEN inhibition and have been shown to contribute to post-injury axonal regrowth in response to PTEN inhibition. Consistently, in an in vitro neuronal ischemia model, BPV enhanced axonal outgrowth of primary cortical neurons after oxygen-glucose deprivation and the enhancing effects were abolished by Akt/mTOR inhibition. In conclusion, delayed BPV treatment improved functional recovery from experimental stroke possibly via enhancing axonal growth and Akt/mTOR activation contributed to BPV-enhanced post-stroke axon growth.
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Vascular dementia (VD), defined as a loss of memory and cognitive function resulting from vascular lesions in the brain, is the second-most-common cause of dementia in the elderly, after Alzheimer's disease. In recent years, research has focused on the pathogenesis of VD, and mitochondrial bioenergetic deficits have been suggested to contribute to VD onset. To further investigate the role of mitochondria in VD, we used a rat model of VD, which involved permanent bilateral occlusion of the common carotid arteries (with a 1-week interval between artery occlusion to avoid an abrupt reduction in cerebral blood flow) leading to chronic cerebral hypoperfusion. ⋯ The ischemia group mitochondria also exhibited decreased respiration coupled to decreased expression and activity of the electron transport chain complex IV (cytochrome c oxidase). These results indicate that the mitochondrial oxidative metabolism is inhibited in the hippocampi of rats following chronic ischemia-induced VD. As the mitochondrial oxidative metabolism deficits, namely mitochondrial bioenergetic deficits directly affect the functions of neurons, it may contribute to VD onset.