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Biological interactions and attenuation of MPTP-induced toxicity in Drosophila melanogaster by Trans-astaxanthin.

Trans-astaxanthin (TA) is a carotenoid with amphipathic chemical structure found in yeast, and aquatic organisms. It is known to possess both antioxidative and anti-inflammatory properties. This study was carried out to investigate the ameliorative action of TA on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in Drosophila melanogaster (Fruit fly). The flies were orally treated with TA (2.5mg/10g diet) and/or MPTP (500µM) for 5 days. Thereafter, we evaluated selected biomarkers of locomotor deficits (acetylcholinesterase (AChE) and negative geotaxis), oxidative stress (hydrogen peroxide (H2O2), protein carbonyls (PC)), antioxidants (total thiols (T-SH), non-protein thiols, glutathione-S-transferase (GST) and catalase), and inflammation (nitric oxide (nitrite/nitrate) in the flies. Furthermore, we investigated molecular docking analysis of TA against Kelch-like ECH-associated protein 1 (Keap1)) of Homo sapiens and D. melanogaster. The results indicated that TA increased MPTP-induced decreased activities of AChE, GST, and catalase, as well as levels of non-protein thiols and T-SH compared with MPTP-treated flies (p<0.05). Furthermore, TA attenuated inflammation, and improved locomotor deficit in the flies. The molecular docking data showed that TA had docking scores for binding both the Human and Drosophila Keap1, nearly closer to or higher than the standard inhibitor. The attenuating effects of TA against MPTP-induced toxicity could arise from its antioxidative and anti-inflammatory properties as well as its chemical structure.

Nerve terminals in the tumor microenvironment as targets for local infiltration analgesia.

Nerve terminals within the tumor microenvironment as potential pain-mitigating targets for local infiltration analgesia is relatively less explored. In this study, we examine the role of key analgesics administered as local infiltration analgesia in a model of cancer-induced bone pain (CIBP). CIBP was induced by administration of allogenic MRMT1 breast cancer cells in the proximal tibia of rats, and tumor mass characterized using radiogram, micro-CT, and histological analysis. In vitro responsiveness to key analgesics δ-opioid receptor agonist (DOPr), Ca2+ channel and TRPV1 antagonists was assessed using ratiometric Ca2+ imaging in sensory neurons innervating the tumor site. Effectiveness of locally infiltrated analgesics administered independently or in combination was assessed by quantifying evoked limb withdrawal thresholds at two distinct sites for up to 14 days. CIBP animals demonstrated DOPr, N-, and L-type and TRPV1 expression in lumbar dorsal root ganglion neurons (DRG), comparable to controls. Evoked Ca2+ transients in DRG neurons from CIBP animals were significantly reduced in response to treatment with compounds targeting DOPr, N-, L-type Ca2+ channels and TRPV1 proteins. Behaviourally, evoked hyperalgesia at the tumor site was strongly mitigated by peritumoral injection of the DOPr agonist and T-type calcium antagonist, via its activity on bone afferents. Results from this study suggest that nerve terminals at tumor site could be utilized as targets for specific analgesics, using local infiltration analgesia.

Detecting passive and active response in patients with behaviourally diagnosed unresponsive wakefulness syndrome.

The diagnosis of unresponsive wakefulness syndrome depends mostly on the motor response following verbal commands. However, there is a potential for misdiagnosis in patients who understand verbal commands (passive response) but cannot perform voluntary movements (active response). To evaluate passive and active responses in such patients, this study used an approach combining functional magnetic resonance imaging and passive listening tasks to evaluate the level of speech comprehension, with portable brain-computer interface modalities that were applied to elicit an active response to attentional modulation tasks at the bedside. We included ten patients who were clinically diagnosed as unresponsive wakefulness syndrome. Two of ten patients showed no significant activation, while limited activation in the auditory cortex was found in six patients. The remaining two patients showed significant activation in language areas, and were able to control the brain-computer interface with reliable accuracy. Using a combined passive/active approach, we identified unresponsive wakefulness syndrome patients who showed both active and passive neural responses. This suggests that some patients with unresponsive wakefulness syndrome diagnosed behaviourally are both wakeful and responsive, and the combined approach is useful for distinguishing a minimally conscious state from unresponsive wakefulness syndrome physiologically.

Open Access
Neuroprotective Role of Calreticulin After Spinal Cord Injury in Mice.

Accumulating evidence suggests that endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in the pathology of spinal cord injury (SCI). To determine the role of the UPR-target molecule in the pathophysiology of SCI, we analyzed the expression and the possible function of calreticulin (CRT), a molecular chaperone in the ER with high Ca2+ binding capacity, in a mouse SCI model. Spinal cord contusion was induced in T9 by using the Infinite Horizon impactor. Quantitative real-time polymerase chain reaction confirmed increase of Calr mRNA after SCI. Immunohistochemistry revealed that CRT expression was observed mainly in neurons in the control (sham operated) condition, while it was strongly observed in microglia/macrophages after SCI. Comparative analysis between wild-type (WT) and Calr+/- mice revealed that the recovery of hindlimb locomotion was reduced in Calr+/- mice, based on the evaluation using the Basso Mouse Scale and inclined-plane test. Immunohistochemistry also revealed more accumulation of immune cells in Calr+/- mice than in WT mice, at the epicenter 3 days and at the caudal region 7 days after SCI. Consistently, the number of damaged neuron was higher in Calr+/- mice at the caudal region 7 days after SCI. These results suggest a regulatory role of CRT in the neuroinflammation and neurodegeneration after SCI.

Learning from illusions: From perception studies to perspective-taking interventions.

Visual illusions have always fascinated people but they have often been confined to the field of entertainment. Although philosophers, psychologists and neuroscientists have used them to explore the bases of human perception and to teach about vision, these attractive tools have still remained largely underexploited. The goal of the present paper is to argue that visual illusions can also serve as a powerful medium to question our relation to the world and to others, as they demonstrate that we do not fully perceive reality and that each interpretation of the world may be equally sound. Further, specific 3D visual illusions, such as 3D ambiguous objects that give rise to two specific interpretations, enable the viewer to realize that their perception is tied to their viewing point, and that this may also apply to social cognition and interactions. Specifically, this low-level embodied experience should generalize to other levels and enhance the consideration of others' perspective independently of the type of representations. Therefore, the use of illusions in general, and 3D ambiguous objects in particular, constitutes an avenue for future interventions designed to increase our perspective-taking abilities and the pacification of social relations through mutual understanding, which is particularly relevant in the current era.