Neuroscience
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Social anxiety is characterized by an intense fear of evaluation from others and/or withdrawal from social situations. Extreme social anxiety can lead to social anxiety disorder. There remains an urgent need to investigate the neural substrates of subclinical social anxiety for early diagnosis and intervention to reduce the risk to develop social anxiety disorder. ⋯ The activation of superficial amygdala and the deactivation of basal forebrain in response to angry condition showed positive correlations with the level of social anxiety. In addition, the resting-state functional connectivity between these two regions was negatively correlated with the level of social anxiety. These results may help to understand the individual difference and corresponding neural underpinnings of social anxiety in the subclinical population, and might provide some insight to develop strategies for early diagnosis and interventions of social anxiety to reduce the risk of deterioration from subclinical to clinical level of social anxiety.
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PR-957 [low molecular mass polypeptide (LMP)-7 selective inhibitor] regulates T helper (Th) cell differentiation and inflammatory response in multiple neurological diseases. Hence, this study aimed to explore the effect of PR-957 on Th1/Th2/Th17 cell differentiation, therapeutic efficacy and its potential mechanisms in Alzheimer's disease (AD). The LMP7 expressions in peripheral blood mononuclear cells from 30 AD patients and 30 healthy controls (HC) were detected. ⋯ SC79 addition upregulated pAKT/AKT expression, Th1 cells, and Th17 cells, while downregulated Th2 cells; also SC79 could alleviate the effect of PR-957 on regulating PI3K/AKT pathway and Th1, Th2, and Th17 cell differentiation in AD CD4+ T cells. Furthermore, PR-957 attenuated cognitive impairment and neurofibrillary tangle; also it inhibited Th17 cell differentiation and PI3K/AKT pathway in the brain and spleen of AD mice. In conclusion, PR-957 suppresses Th1 and Th17 cell differentiation, attenuates neural injury and improves cognitive function via inactivating PI3K/AKT pathway in AD.
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Impulsivity is a personality trait of healthy individuals, but in extreme forms common in mental disorders. Previous behavioral testing of wild-caught bank voles and wood mice suggested impulsiveness in bank voles. Here, we compared behavioral performance of bank voles and wood mice in tests for response control in the IntelliCage. ⋯ Corticosterone measurements at the end of experiments suggested that IntelliCage testing did not elicit a stress response in these wild rodents. In summary, habenular size differences and altered activation of brain areas after testing might indicate differently balanced activations of cortico-limbic and cortico-hypothalamic circuits in bank voles compared to wood mice. Behavioral performance of bank voles suggest that these rodents could be a natural animal model for investigating impulsive and perseverative behaviors.
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Noisy galvanic vestibular stimulation has been shown to improve vestibular perception in healthy subjects. Here, we sought to obtain similar results using more natural stimuli consisting of small-amplitude motion perturbations of the whole body. Thirty participants were asked to report the perceived direction of antero-posterior sinusoidal motion on a MOOG platform. ⋯ At the individual level, the threshold was lower with at least one noise level than the threshold without noise in 87% of participants. Thus, small, stochastic oscillations of the whole body can increase the probability of recognizing the direction of motion from low, normally subthreshold vestibular signals, possibly due to stochastic resonance mechanisms. We suggest that, just as the external noise of the present experiments, also the spontaneous random oscillations of the head and body associated with standing posture are beneficial by enhancing vestibular thresholds with a mechanism similar to stochastic resonance.
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Gastrin-releasing peptide (GRP) in the spinal dorsal horn acts on the GRP receptor, and this signalling mechanism has been strongly implicated in itch. However, the source of GRP in the dorsal horn is not fully understood. For example, the BAC transgenic mouse line GRP::GFP only captures around 25% of GRP-expressing cells, and Grp mRNA is found in several types of excitatory interneuron. ⋯ Cell bodies and axons of all GRP-GFP cells were labelled, confirming reliability of the antibodies. Among the other populations, we found the highest degree of co-expression (>50%) in axons of NPFF-expressing cells, while this was somewhat lower (10-20%) in cells that expressed substance P and NKB, and much lower (<10%) in other classes. Our findings show that these antibodies reliably detect GRP-expressing neurons and axons, and that in addition to the GRP-GFP cells, excitatory interneurons expressing NPFF or substance P are likely to be the main source of GRP in the spinal dorsal horn.