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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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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Meta Analysis
Functional and Structural Abnormalities in the Pain Network of Generalized Anxiety Disorder Patients with Pain Symptoms.
Pain symptoms significantly impact the well-being and work capacity of individuals with generalized anxiety disorder (GAD), and hinder treatment and recovery. Despite existing literature focusing on the neural substrate of pain and anxiety separately, further exploration is needed to understand the possible neuroimaging mechanisms of the pain symptoms in GAD patients. We recruited 73 GAD patients and 75 matched healthy controls (HC) for clinical assessments, as well as resting-state functional and structural magnetic resonance imaging scans. ⋯ Further correlation analysis revealed a positive correlation between ReHo of the left anterior insula and pain scores in GAD patients, while a respective negative correlation between GMV of the bilateral thalamus and PHQ-15 scores. In summary, GAD patients exhibit structural and functional abnormalities in pain-related networks. The enhanced ReHo in the left anterior insula is correlated with pain symptoms, which might be a crucial brain region of pain symptoms in GAD.
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In males but not in females, brain derived neurotrophic factor (BDNF) plays an obligatory role in the onset and maintenance of neuropathic pain. Afferent terminals of injured peripheral nerves release colony stimulating factor (CSF-1) and other mediators into the dorsal horn. These transform the phenotype of dorsal horn microglia such that they express P2X4 purinoceptors. ⋯ Possible mechanisms promoting the preferential release of BDNF in pain signaling structures are discussed. In females, invading T-lymphocytes increase dorsal horn excitability but it remains to be determined whether similar processes operate in supra-spinal structures. Despite its ubiquitous role in pain aetiology neither BDNF nor TrkB receptors represent potential therapeutic targets.