Neuroscience
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Autism Spectrum Disorders (ASD) and schizophrenia are distinct neurodevelopmental disorders that share certain symptoms and genetic components. Both disorders show abnormalities in dendritic spines, which are the main sites of excitatory synaptic inputs. Recent studies have identified the synaptic scaffolding protein Shank3 as a leading candidate gene for both disorders. ⋯ We identified shared and distinct phenotypes in dendritic spine morphogenesis and plasticity in the ASD-associated InsG3680 mutant mice and the schizophrenia-associated R1117X mutant mice. No significant changes in dendritic arborization were observed in either mutant, raising the possibility that synaptic dysregulation may be a key contributor to the behavioral defects previously reported in these mice. These findings shed light on how patient-linked mutations in SHANK3 affect dendritic spine dynamics in the developing brain, which provides insight into the synaptic basis for the distinct phenotypes observed in ASD and schizophrenia.
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The glymphatic system is important for waste removal in the central nervous system. It removes soluble proteins and metabolic waste under the action of aquaporin-4 (AQP4) at the end of astrocytes. The glymphatic system plays a role in numerous neurological diseases; however, the relationship between migraine and the glymphatic system remains unclear. ⋯ Then, further suppression of glymphatic function by TGN-020 (an AQP4 blocker) aggravated the migraine pathological changes in mice. The results indicated that glymphatic dysfunction may aggravate migraine pathology. Therefore, our findings revealed the potential role of the glymphatic system in migraine, providing possible targets for migraine prevention and treatment.
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Mapping variability in cortical spontaneous activity (CSA) is an essential goal of understanding various sources of dark brain energy in human neuroscience. CSA was traditionally characterized using resting-state functional MRI (rfMRI) at 1.5T or 3T magnets while recently with 7T-rfMRI. However, the utility and interpretability of 7T-rfMRI must first be established for its variability. ⋯ These effects were primarily located in the high-order associate cortex, parsing the corresponding changes in individual differences with respect to 7T-rfMRI: (1) higher connectivity variability between participants and the lower connectivity variability within individual participants, and (2) lower amplitude variability between participants and higher amplitude variability within participants. Our work, for the first time, demonstrated the variability of the human CSA across space, rfMRI settings/platforms, and individuals. We discussed the statistical implications of our findings on CSA-based experimental designs and reproducible neuroscience as well as their translational value for personalized applications.
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Proteinase-activated receptor-1 (PAR1) is expressed in astrocytes of various brain regions, and its activation is involved in the modulation of neuronal activity. Here, we report effects of PAR1 selective agonist TFLLR on respiratory rhythm generation in brainstem-spinal cord preparations. Preparations were isolated from newborn rats (P0-P4) under deep isoflurane anesthesia and were transversely cut at the rostral medulla. ⋯ In conclusion, activation of astrocytes via PAR1 resulted in a decrease of inspiratory C4 burst rate in association with transient hyperpolarization of respiratory-related neurons. After washout, slow and weak excitatory responses appeared. Adenosine may be partially involved in the inhibitory effect of PAR1 activation.