Neuroscience
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G-protein coupled receptors (GPCRs) modulate brain function by signaling through heterotrimeric Gq/11, Gs, and Gi/o protein subtypes. Researchers frequently study neuromodulation via these GPCR-subtypes on a 'cell-by-cell' basis. Although useful to explore a small number of interactions among neuromodulatory systems under controlled settings, this approach fails to account for a global organization of GPCRs in the brain. ⋯ Correlation strength increased with age but dropped when randomly removing genes from their corresponding groups. These findings suggest that the expression patterns of GPCR subtypes and receptor families are intricately intertwined. Well-orchestrated interactions by neuromodulatory-GPCR ensembles could be crucial for the brain to function as a highly integrated complex system.
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Brain EGR1 (early growth response protein 1) overexpression aggravates focal ischemic brain injury, but its role in intracerebral hemorrhage (ICH) induced cerebral injury remains obscure. In this study, a rat ICH model was established by injecting type VII collagenase into the brain, and EGR1 knockdown reversed the increase of hematoma area, neurological function score, brain water content, blood-brain barrier (BBB) permeability, inflammation, p300 and retinoid a X receptor-α (RXRα) protein levels, as well as RXRα acetylation level induced by ICH. EGR1 expression was up-regulated in primary brain microvascular endothelial cells (BMECs), neurons, and astrocytes after ICH induction, and the up-regulation was most significant in BMECs. ⋯ Furthermore, the STAT3/NF-κB pathway was activated after treatment with OGD plus hemin, which was suppressed by silencing EGR1. Treatment with Stattic (an inhibitor of STAT3) restrained the effect of OGD plus hemin on NF-κB pathway activity, inflammation, cell viability and TEER. In conclusion, EGR1 increased RXRα acetylation level by regulating p300, thereby aggravating brain damage in ICH rat model and dysfunction in BMECs, Through the STAT3/NF-κB pathway.
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Optic neuritis and retinal damage are common manifestations of multiple sclerosis (MS). Pterostilbene (PT) has been used to treat multiple diseases for its anti-inflammatory, anti-apoptosis and neuroprotective activities. This study aimed to investigate whether PT exerts a therapeutic effect on optic neuritis and retinal damage triggered by MS. ⋯ In addition, PT activated SIRT1 signaling in the optic nerves and retina. Notably, EX-527, an inhibitor of SIRT1, reversed the effect of high-dose PT on the optic nerves and retina, indicating that PT exerted the protective effect via activating SIRT1 signaling. This study provides a potential candidate for treating MS.
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Thalamocortical dysfunction is thought to underlie the pathophysiology of chronic pain revealed by electroencephalographic studies. The thalamus serves as a primary relay center to transmit sensory information and motor impulses via dense connections with the somatosensory and motor cortex. In this study, diffusion tensor imaging (DTI) (probabilistic tractography) and resting-state functional magnetic resonance imaging (functional connectivity) were used to characterize the anatomical and functional integrity of the thalamo-sensorimotor pathway in chronic low back pain (cLBP). ⋯ Moreover, there was significantly altered resting-state functional connectivity (rsFC) of bilateral thalamo-motor/somatosensory pathways in patients with cLBP as compared to healthy controls. We also detected a significant correlation between pain intensity during the MRI scan and rsFC of the right thalamo-somatosensory pathway in cLBP. Our findings highlight the involvement of the thalamo-sensorimotor circuit in the pathophysiology of cLBP.
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Although altered microstructure properties of white-matter tracts have been reported in children with attention-deficit/hyperactivity disorder (ADHD), findings from relatively few adult ADHD studies are inconsistent. This study aims to examine microstructural property over the whole brain in adults with ADHD and explore structural connectivities. Sixty-four medication-naïve adults with ADHD and 81 healthy adults received diffusion spectrum imaging. ⋯ Adults with ADHD had increased mGFA values in the segments located in the left frontal aslant tract, the right inferior longitudinal fasciculus, and the left perpendicular fasciculus, and reduced mGFA values in the segments located in the right superior longitudinal fasciculus (SLF) I, the left SLF II, the right frontostriatal tracts from dorsolateral prefrontal cortex and the ventrolateral prefrontal cortex, the right medial lemniscus, the right inferior thalamic radiation to the auditory cortex, and the callosal fibers. Additionally, the mGFA value of the right SLF I segment was associated with hyperactivity-impulsivity symptoms. Our findings suggest that white-matter tracts with altered microstructure properties are located within the attention networks, fronto-striato-thalamocortical regions, and those associated with attention and visual perception in adults with ADHD.