Neuroscience
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The aims of this study were to examine the levels of serum and exosomal miR-137, miR-155 and miR-223, three neuroinflammation-related miRNAs, in dementia patients and to explore the value of these miRNAs for the diagnosis and prognostic evaluation of dementia. Thirty-two patients with dementia were enrolled, and sixteen volunteers without dementia served as controls. Serum exosomes were isolated by precipitation with ExoQuick and characterized by western blotting, nanoparticle-tracking analysis and immunofluorescence microscopy. ⋯ The level of miR-223 was significantly correlated with Mini-Mental State Examination (MMSE) scores, Clinical Dementia Rating (CDR) scores, magnetic resonance spectroscopy (MRS) spectral ratios and serum concentrations of IL-1β, IL-6, TNF-α, and CRP. The diagnostic utility of exosomal miR-233 was evaluated by the area under the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was 0.875. This study suggests that serum exosomal miR-223 is a promising biomarker for diagnosing dementia and evaluating the progression of disease.
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Brain CYP2D is responsible for the synthesis of endogenous neurotransmitters such as dopamine and serotonin. This study is to investigate the effects of cerebral CYP2D on mouse behavior and the mechanism whereby growth hormone regulates brain CYP2D. The inhibition of cerebellar CYP2D significantly affected the spatial learning and exploratory behavior of mice. ⋯ Pulsatile GH decreased the binding of PPARα to the CYP2D6 promoter by 40% and promoted the binding of PPARγ to the CYP2D6 promoter by approximately 60%. The male GH secretory pattern altered PPAR expression and the binding of PPARs to the CYP2D promoter, leading to the elevation of brain CYP2D in a tissue-specific manner. Growth hormone may alter the learning and memory functions in patients receiving GH replacement therapy via brain CYP2D.
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Previous studies have reported the essence of the sensory-based properties of human brain function, in which mental imagery is of great importance. In this study, we explored the association between the activities of two special regions, i.e., the primary visual area (PVA), which is the classically dominant sensory region, and the default mode network (DMN), which is the classical supra-sensory region, with a focus on their linkage in visual mental imagery. For this purpose, we collected fMRI data from 30 healthy participants (15 males; 22.37 ± 2.52 years) during the resting state and a mental rotation task state. ⋯ Furthermore, the results showed the steady and tight intrinsic association between the activities of the PVA and the DMN, with the prefrontal cortex and the MTL regions being found to be consistently involved in the resting-state brain. It also was suggested that the observed association between the PVA and the DMN was highly reproducible for the mental rotation task. Together, these observations, from the perspective of visual mental imagery, provided experimental evidence for the robustness and stability of the detailed map of the associations between the activities of the PVA and the DMN.
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Human amyloid β1-42 (hAβ1-42) peptides are known to self-aggregate into oligomers that contribute to the degeneration of neurons and development of Alzheimer's disease (AD) pathology. Unlike humans, rodents do not develop AD, possibly due to differences in three amino acids (R5G, Y10F and H13R) within the hydrophilic N-terminal domain of Aβ1-42. This is partly supported by evidence that hAβ1-42 is more prone to fibrillization and has a higher cellular toxicity than rodent Aβ1-42 (rAβ1-42). ⋯ Interestingly, the mutants are still able to aggregate into oligomers, which are predominantly larger than those comprised of hAβ1-42. Our cell viability experiments further showed a rank order of oligomer toxicity of hAβ1-42 > rAβ1-42 ≫ mutant Aβ1-42, suggesting that toxicity can be influenced by N-terminal Aβ1-42 mutations via reduction of fibril formation and/or alteration of oligomer size. These results, taken together, confirm that N-terminal mutations can affect Aβ fibril and oligomer formation with reduced toxicity despite lying outside the core amyloid region of Aβ peptide.