Neuroscience
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Traumatic brain injury (TBI) is a frequent and clinically highly heterogeneous neurological disorder with large socioeconomic consequences. NeuroAid (MLC601 and MLC901), a Traditional Medicine used in China for patients after stroke has been previously reported to induce neuroprotection and neuroplasticity. This study was designed to evaluate the neuroprotective and neuroregenerative effects of MLC901 in a rat model of TBI. ⋯ Furthermore, MLC901 reduced cognitive deficits induced by TBI. Rats subjected to TBI displayed a suppression of temporal order memory, which was restored by MLC901. This work provides evidence that MLC901 has neuroprotective and neurorestorative actions, which lead to an improvement in the recovery of cognitive functions in a model of traumatic brain injury.
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Electrocortical and hemodynamic measures reliably identify enhanced activity in the ventral and dorsal visual cortices during the perception of emotionally arousing versus neutral images, an effect that may reflect directive feedback from the subcortical amygdala. However, other brain regions strongly modulate visual attention, such as frontal eye fields (FEF) and intraparietal sulcus (IPS). Here we employ rapid sampling of BOLD signal (4 Hz) in the amygdala, fusiform gyrus (FG), FEF and IPS in 42 human participants as they viewed a series of emotional and neutral natural scene photographs balanced for luminosity and complexity, to test whether emotional discrimination is evident in dorsal structures prior to such discrimination in the amygdala and FG. ⋯ Granger causality estimates yield stronger directional connectivity from IPS to FEF than the reverse in this emotional picture paradigm. Consistent with a reentrant perspective of emotional scene perception, greater directional connectivity was found from the amygdala to FG compared to the reverse. These data support a perspective in which the registration of emotional scene content is orchestrated by the amygdala and rostral inferotemporal visual cortex.
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Evidence is emerging that reactive oxygen species (ROS)-induced oxidative stress has a crucial role in the pathogenesis of neurodegenerative diseases. To find the effective therapies for neurodegenerative diseases, evaluation of the relevant molecular mechanisms is necessary. In the current study, we investigated the effects of hydrogen peroxide (H2O2)-induced oxidative stress on SK-N-MC cell death with focus on HIF-1α, Foxo3a and Notch1 signaling factors. ⋯ In contrast, Notch inhibition resulted in HIF-1α/Foxo3a signaling pathway up-regulation, suggesting the bidirectional crosstalk between HIF-1α and Notch1. These results collectively suggest that ROS are involved in activation of both the defensive and pro-apoptotic pathways encompassing HIF-1α and p53, respectively. Regarding the HIF-1α-mediated neuroprotection role, elucidation of the molecular mechanism would certainly be essential for effective drug design against neurodegenerative diseases.
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Inflammation mediated by glial activation appears to play a critical role in the pathogenesis of Parkinson disease (PD). Glia maturation factor (GMF), a proinflammatory protein predominantly localized in the central nervous system was isolated, sequenced and cloned in our laboratory. We have previously demonstrated immunomodulatory and proinflammatory functions of GMF, but its involvement in 1-methyl-4-phenylpyridinium (MPP(+)), active metabolite of classical parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), inducing loss of dopaminergic (DA) neurons has not been studied. ⋯ Subsequently, GMF deficiency ameliorates antioxidant balance, as evidenced by the decreased level of lipid peroxidation, less ROS production along with increased level of glutathione; and attenuated the DA neuronal loss via the downregulation of NF-κB-mediated inflammatory responses. In conclusion, our overall data indicate that GMF modulates oxidative stress and release of deleterious agents by MPP(+) leading to loss of DA neurons. Our study provides new insights into the potential role of GMF and identifies targets for therapeutic interventions in neurodegenerative diseases.
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γ-Hydroxybutyrate (GHB) has a complex array of neural actions that include effects on its own high-affinity GHB receptor, the release of neuroactive steroids, and agonist actions at GABAA and GABAB receptors. We previously reported partial overlap in the c-Fos expression patterns produced by GHB and the GABAB agonist, baclofen in rats. The present study extends these earlier findings by examining the extent to which GHB Fos expression and behavioral sedation are prevented by (2S)-(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911), a GABAB antagonist, and NCS-382, a putative antagonist at the high-affinity GHB receptor. ⋯ SCH 50911 alone affected the Islands of Calleja and the medial, central and paraventricular thalamic nuclei. Overall, this study shows a surprising lack of reversal of GHB-induced Fos expression by two relevant antagonists, both of which have marked intrinsic actions. This may reflect the limited doses tested but also suggests that GHB Fos expression reflects mechanisms independent of GHB and GABAB receptors.