Neuroscience
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Transient receptor potential vanilloid 1 (TRPV1)-containing afferent neurons convey nociceptive signals and play an essential role in pain sensation. Exposure to nerve growth factor (NGF) rapidly increases TRPV1 activity (sensitization). In the present study, we investigated whether treatment with the selective cannabinoid receptor 1 (CB1) agonist arachidonyl-2'-chloroethylamide (ACEA) affects NGF-induced sensitization of TRPV1 in adult mouse dorsal root ganglion (DRG) afferent neurons. ⋯ Further, pretreatment with ACEA inhibited NGF-induced phosphorylation of AKT. Blocking PI3 kinase activity also attenuated the NGF-induced increase in the number of neurons that responded to capsaicin. Our results indicate that the analgesic effect of CB1 activation may in part be due to inhibition of NGF-induced sensitization of TRPV1 and also that the effect of CB1 activation is at least partly mediated by attenuation of NGF-induced increased PI3 signaling.
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Evidence from the animal literature suggests that post-training glucocorticoids (GCs) interact with noradrenergic activation at acquisition to enhance memory consolidation for emotional stimuli. While there is evidence that GCs enhance memory for emotional material in humans, the extent to which this depends on noradrenergic activation at encoding has not been explored. In this study, 20-mg hydrocortisone was administered to healthy young women (18-35 yrs old) in a double-blind fashion 10 min prior to viewing a series of emotional and neutral images. ⋯ Participants returned 1 week later for a surprise recall test. Results suggest that, hydrocortisone administration resulted in emotional memory enhancement only in participants who displayed an increase in endogenous noradrenergic activation, measured via salivary alpha-amylase at encoding. These results support findings in the animal literature, and suggest that GC-induced memory enhancement relies on noradrenergic activation at encoding in women.
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In sentences such as dogs cannot fly/bark, evaluation of the truth-value of the sentence is assumed to appear after the negation has been integrated into the sentence structure. Moreover negation processing and truth-value processing are considered effortful processes, whereas processing of the semantic relatedness of the words within sentences is thought to occur automatically. In the present study, modulation of event-related brain potentials (N400 and late positive potential, LPP) was investigated during an implicit task (silent listening) and active truth-value evaluation to test these theoretical assumptions and determine if truth-value evaluation will be modulated by the way participants processed the negated information implicitly prior to truth-value verification. ⋯ However, during active evaluation, processing of semantically-unrelated but true targets (TN) elicited larger N400 and LPP amplitudes as well as a pronounced frontal negativity. This pattern was particularly prominent in those 11 individuals, whose N400 modulation during silent listening indicated that they were more sensitive to violations of the truth-value than to semantic priming effects. The results provide evidence for implicit truth-value processing during silent listening of negated sentences and for task dependence related to inter-individual differences in implicit negation processing.
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Depressive symptoms are frequent in idiopathic restless legs syndrome (RLS). However, little is known, so far, about the neurological basis. The present study aimed to explore the neuroanatomical anomalies in depressed drug-naïve RLS patients using voxel-based morphometry (VBM) analysis. ⋯ Depressive symptoms are associated with GM anomalies in ACC in patients with RLS. We propose that ACC is perhaps an important neuroimaging marker for facilitating treatment strategies in patients with RLS when assessing depressive symptoms.
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Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disease characterized by the loss of motor neurons in the motor cortex, brain stem and spinal cord. Currently, there is no cure for this lethal disease. Although the mechanism underlying neuronal cell death in ALS remains elusive, growing evidence supports a crucial role of endoplasmic reticulum (ER) stress in the pathogenesis of ALS. ⋯ The results also revealed a significant decrease in the levels of the ER chaperone glucose-regulated protein 78 (BiP/Grp78) and markers of another two ER stress pathways, activating transcription factor 6α (ATF6α) and inositol-requiring enzyme 1 (IRE1). In addition, guanabenz increased the protein levels of anti-apoptotic B cell lymphoma/lewkmia-2 (Bcl-2), and down-regulated the pro-apoptotic protein levels of C/EBP homologous protein (CHOP), Bcl-2-associated X protein (BAX) and cytochrome C in SOD1 G93A mice. Our findings indicate that guanabenz may represent a novel therapeutic candidate for the treatment of ALS, a lethal human disease with an underlying mechanism involving the attenuation of ER stress and mitochondrial stress via prolonging eIF2α phosphorylation.