Neuroscience
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Clinical observations suggested that gamma-hydroxybutyrate (GHB) protects nerve cells against death but the direct proofs are missing. Here, we combined several approaches to investigate GHB capacity to protect human neuroblastoma SH-SY5Y cells against hydrogen peroxide (H2O2)-induced death. To increase the patho-physiological relevancy of our study, we used native SH-SY5Y cells and SH-SY5Y cells stably transfected with the wild-type amyloid-precursor-protein (APPwt) or control-vector-pCEP4. ⋯ Interestingly, GHB, which strongly decreased elevated basal levels of TUNEL-staining, activated caspase 3-labeling and Bax/Bcl-2 in APPwt-transfected cells, also counteracted H2O2-evoked increased apoptotic markers in native and genetically modified SH-SY5Y cells. Since GHB did not promote cell proliferation, anti-apoptotic action through the down-regulation of Bax/Bcl-2 ratios and/or caspase 3 activity appears as a critical mechanism involved in GHB-induced protection of SH-SY5Y cells against APPwt-overexpression- or H2O2-evoked death. Altogether, these results, providing multi-parametric evidence for the existence of neuroprotective action of GHB, also open interesting perspectives for the development of GHB analog-based strategies against neurodegeneration or nerve cell death.
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Under normal and dietary iron deficiency conditions, the BXD recombinant inbred (RI) strains of mice show large variations in regional brain iron concentration, particularly in the ventral midbrain (VMB). In a study utilizing just one of the BXD strains, diurnal changes in subregional brain iron concentration were found, which were dependent on the brain region and sex of the mice. The focus of this study was to determine if diurnal changes in VMB can be found across other BXD RI strains and whether a diurnal effect would be common to all strains or variable across strains similar to the large strain variability in iron concentrations determined during the first part of the light phase. ⋯ In conclusion, significant brain-regional-specific diurnal changes in total iron concentrations were found in a selection of BXD RI mice. Sex and strain are functional determinates of which regions will be affected and in what direction the affect will be. The study provides an animal model for future work into determining the biological and genetic basis of circadian influences on VMB iron homeostasis.
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A main component of St. John's Wort (Hypericum perforatum, HP) is hyperforin which has antioxidant properties in dorsal root ganglion (DRG) neurons, due to its ability to modulate NADPH oxidase and protein kinase C. Recent reports indicate that oxidative stress through NADPH oxidase activates TRPM2 channels. ⋯ Glutathione peroxidase activity and GSH values in the DRG were high in HP, 2-APB and V+D groups although lipid peroxidation level was low in the groups. In conclusion, we observed a protective role for HP on Ca(2+) entry through a TRPM2 channel in the DRG neurons. Since over-production of oxidative stress and Ca(2+) entry are implicated in the pathophysiology of neuropathic pain and neuronal inflammation, our findings may be relevant to the etiology and treatment of neuropathology in DRG neurons.
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Placebo treatment can alter brain activation in regions implicated in affective processing and cognitive control of emotions. This functional magnetic resonance imaging (fMRI) study investigated whether a placebo can additionally modulate visual cortex activity and connectivity during affective picture perception. ⋯ This was accompanied by a reduced activation of the primary visual cortex, which showed reduced interaction with the amygdala and the insula. Accordingly, placebos are able to affect basic perceptive processes.
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Cannabinoid receptor type 1 (CB1)-dependent signaling in the brain is known to modulate food intake. Recent evidence has actually shown that CB1 can both inhibit and stimulate food intake in fasting/refeeding conditions, depending on the specific neuronal circuits involved. However, the exact brain sites where this bimodal control is exerted and the underlying neurobiological mechanisms are not fully understood yet. ⋯ Furthermore, local CB1 blockade in the PVN also increases the orexigenic effect of the gut hormone ghrelin in animals fed ad libitum. At the electrophysiological level, CB1 blockade in slices containing the PVN potentiates the decrease of the activity of PVN neurons induced by long-term application of ghrelin. Hence, the PVN is (one of) the site(s) where signals associated with the body's energy status determine the direction of the effects of endocannabinoid signaling on food intake.