Neuroscience
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The Aβ hypothesis has long been central to Alzheimer's disease (AD) theory, with a recent surge in attention following drug approvals targeting Aβ plaque clearance. Aβ42 oligomers (AβO) are key neurotoxins. While β-amyloid (Aβ) buildup is a hallmark of AD, postmortem brain analyses have unveiled human islet amyloid polypeptide (hIAPP) deposition in AD patients, suggesting a potential role in Alzheimer's pathology. ⋯ These findings provide compelling evidence for the heightened toxicity of Aβ42-hIAPP co-oligomers on neurons and their role in exacerbating AD pathology. The study contributes novel insights into the pathogenesis of Alzheimer's disease, highlighting the potential involvement of hIAPP in AD pathology. Together, these findings offer novel insights into AD pathogenesis and routes for constructing animal models.
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Down syndrome (DS), also known as trisomy 21, is one of the most common chromosomal disorders associated with intellectual disability. Mouse models are valuable for mechanistic and therapeutic intervention studies. The purpose of this study was to investigate astroglial anomalies in Dp16, a widely used DS mouse model. ⋯ However, after treatment with lipopolysaccharides, the inflammatory response gene IFNβ increased significantly more in Dp16 astrocytes than in WT astrocytes. Overall, our results showed that the increase in astrogliogenesis in DS was not apparent in the early life of Dp16 mice, while astrocyte activation, which may be partly caused by increased responses to inflammatory stimulation, was significant. The inflammatory response of astrocytes might be a potential therapeutic target for DS intellectual disability.
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Ghrelin, a hormone secreted by the stomach, binds to the growth hormone secretagogue receptor (GHSR) in various brain regions to produce a number of behavioral effects that include increased feeding motivation. During social defeat stress, ghrelin levels rise in correlation with increased feeding and potentially play a role in attenuating the anxiogenic effects of social defeat. One region implicated in the feeding effects of ghrelin is the ventral tegmental area (VTA), a region implicated in reward seeking behaviors, and linked to social defeat in mice. ⋯ Vehicle-treated mice increased their caloric intake during social defeat, but JMV2959-infusions attenuated feeding responses and increased anxiety-like behaviors. The data suggest that GHSR signalling in the VTA is critical for the increases in appetite observed during chronic social defeat stress. Furthermore, these data support the idea that GHSR signaling in the VTA may also have anxiolytic effects, and blocking GHSR in this region may result in an anxiety-like phenotype.
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Evidence suggests that dopamine activity provides a US-related prediction error for Pavlovian conditioning and the reinforcement signal supporting the acquisition of habits. However, its role in goal-directed action is less clear. There are currently few studies that have assessed dopamine release as animals acquire and perform self-paced instrumental actions. ⋯ More recently, evidence has also emerged for a hemispherically lateralised signal associated with the action; dopamine release is greater in the hemisphere contralateral to the spatial target of the action. This effect emerges over the course of acquisition and appears to reflect the strength of the action-outcome association. Thus, during goal-directed action, dopamine release signals the action, the outcome and their association to shape the learning and performance processes necessary to support this form of behavioral control.
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Task switching refers to a set of cognitive processes involved in shifting attention from one task to another. In recent years, researchers have applied transcranial direct current stimulation (tDCS) to investigate the causal relationship between the parietal cortex and task switching. However, results from available studies are highly inconsistent. ⋯ For unpredictable task switching, under the sham condition, the P2 peak was significantly larger for switch trials compared with repeat trials, whereas this difference was not observed under the RA condition. These results indicated the causal relationship between the right parietal cortex and exogenous adjustment processes involved in task switching. Moreover, anodal tDCS over the right parietal cortex may lead to the manifestation of gender differences.