Brain research
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Astaxanthin (ATX), the most abundant flavonoids in propolis, has been proven to exert neuroprotective property against glutamate-induced neurotoxicity and ischemia-reperfusion-induced apoptosis. Previous study have revealed that ATX can rescue PC12 cells from Aβ(25-35)-induced apoptotic death. However, the mechanisms by which ATX mediates its therapeutic effects in vitro are unclear. ⋯ Because the inhibitor of HO-1 activity, ZnPP reversed the protective effect of ATX against Aβ(25-35)-induced cell death. We also demonstrated that the specific ERK inhibitor, PD98059, concentration-dependently blocked on ATX-induced HO-1 expression, and meanwhile PD98059 reversed the protective effect of ATX against Aβ25-35-induced cell death. Taken together, these findings suggest that astaxanthin can induce HO-1 expression through activation of ERK signal pathways, thereby protecting the SH-SY5Y cells from Aβ(25-35)-induced oxidative cell death.
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Rotenone, a mitochondrial complex 1 inhibitor, causes oxidative damage via production of reactive oxygen species. We examined the pathophysiology of neuronal and glial cells of the nigrostriatal pathway following unilateral infusion of varying doses of rotenone into the substantia nigra or medial forebrain bundle of adult male Sprague-Dawley rats, sacrificed 14 and 60 days after infusion. Immunofluorescence techniques were used to qualitatively and quantitatively assay dopaminergic neurons, their projections, glial cells, synapses, and oxidative stress. ⋯ The infusion of 0.5μg of rotenone also caused an increase in astrocytes and microglial cells in the substantia nigra in comparison to control (p≤0.01). We examined the time-dependent reduction of tyrosine hydroxylase-positive nerve fibres and cell bodies in the striatum and substantia nigra respectively, with a progressive reduction evident 60days after infusion (p≤0.01, p≤0.05). Dopaminergic axons exposed to low-dose rotenone undergo oxidative stress, with a resultant ongoing loss of dopaminergic neurons, providing an animal model relevant to Parkinson disease.
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Placebo analgesia has been shown to be driven by expectations of treatment effects. We suggest that the expectation of treatment creates uncertainty about the sensory information of pain. We tested the hypothesis that in placebo responders uncertainty generated by expectations generalizes to other cognitive processes by recruiting participants for a placebo study who had previously taken part in a visual cue-picture decision making perceptual task. ⋯ Electroencephalography (EEG) was used to measure pain evoked potentials to laser heat to determine if the behavioural misperception of pain translated into a physiological response. Regression models showed that both behavioural and physiological placebo responses could be predicted by participants' scores of acquiescence in the cue-picture decision making task. Placebo analgesia seems to be influenced by a cognitive style that assimilates responses to expectations increasing the chances of error when detecting discrepant sensory information.
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Issues related to the intra-cerebral delivery of glial cell line-derived neurotrophic factor (GDNF) have hampered its progression as a neuroprotective therapy for Parkinson's disease. Ex vivo gene therapy, where cells are virally transduced in vitro to produce a specific protein, may circumvent some of the problems associated with direct delivery of this neurotrophin to the brain. In this regard, bone marrow-derived mesenchymal stem cells (MSCs) offer an ideal cell source for ex vivo gene therapy because they are easily isolated from autologous sources, they are amenable to viral transduction and expansion in vitro, and they are hypoimmunogenic and non-tumourigenic in the brain. ⋯ Rats received intrastriatal transplants of GDNF-transduced MSCs 4days prior to induction of an intrastriatal 6-hydroxydopamine lesion. Quantitative tyrosine hydroxylase immunohistochemical staining revealed that GDNF-transduced MSCs were capable of inducing a pronounced local trophic effect in the denervated striatum which was evident by sprouting from the remaining dopaminergic terminals towards the neurotrophic milieu created by the transplanted cells. This strengthens the candidacy of MSCs as vehicles to deliver neurotrophins to the Parkinsonian brain.
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Male animals exhibit greater neuronal damage following focal cerebral ischemic injury in many experimental injury models, however the mechanism of this is unknown. This study used cardiac arrest and cardiopulmonary resuscitation (CA/CPR) in male mice exposed to physiological vs. pharmacological doses of testosterone and tested the hypothesis that testosterone increases damage following global cerebral ischemia. Analysis of histological damage 72h after resuscitation revealed a complex dose-response curve for testosterone, such that low and high doses of testosterone exacerbated ischemic neuronal damage, while intermediate doses had no effect on neuronal survival. ⋯ Finally, the androgen receptor antagonist flutamide inhibited the increase in neuronal damage and sensorimotor impairment observed in testosterone treated mice. Our data showed that low and supra-physiological levels of testosterone increase neuronal damage following global cerebral ischemia and that blockade of androgen receptors limits this injury. Therefore, this study indicated that testosterone may have a role in determining sex-linked differences in cerebrovascular disease as well as having important health implications in clinical conditions of elevated testosterone.