Neuroreport最新文献

The present study aimed to investigate the therapeutic effects of electroacupuncture (EA) on chronic cerebral hypoperfusion (CCH). We first applied the Morris water maze approach to determine the effects of EA and TGN-020 [an inhibitor of aquaporin 4 (AQP4)] on the learning and memory ability of CCH rats. The hematoxylin and eosin, and Nissl staining were further used to investigate the effects of EA and TGN-020 on the neuropathological changes of the dentate gyrus. Next, the ELISA kits were adopted to determine the effects of EA and TGN-020 on the content of amyloid-beta (Aβ) in the cerebrospinal fluid of CCH rats. Finally, we respectively employed technologies of immunohistochemical staining, quantitative real-time PCR, and Western blot to further explore the effects of EA and TGN-020 on the mRNA expression level of amyloid precursor protein (APP) and AQP4 as well as the protein expression level of Aβ1-42 and AQP4 in the dentate gyrus of CCH rats. Our results indicated that EA not only enhanced the learning and memory abilities of CCH rats but also improved the neuropathological damages of CCH rats by upregulating the mRNA and protein expression level of AQP4 to reduce the accumulation of Aβ, especially for the reduction of the mRNA expression level of APP and the protein expression level of Aβ1-42, but TGN-020 effectively reversed the therapeutic effects mentioned above of EA. In summary, we proved that EA, as the activator of AQP4, prevents the accumulation of Aβ during the treatment of CCH.

This study aimed to investigate the potential of electroacupuncture as an intervention for inducing 'Awakening and Opening of the Brain' in rats with stroke models induced by middle cerebral artery occlusion/reperfusion (MCAO/R). The efficacy of electroacupuncture in alleviating cerebral ischemic injury was evaluated using Longa scores, triphenyl tetrazolium chloride staining, and hematoxylin and eosin staining. Non-targeted metabolomics analysis was conducted to identify differential metabolite changes before and after electroacupuncture treatment in MCAO/R rats. Network pharmacology analysis was then performed to correlate these differential metabolites with ischemic stroke. The PI3K/AKT/NF-κB signaling pathway was identified as a key target. In vivo experiments further validated the mechanism by which electroacupuncture promotes M2 microglial polarization through inhibition of the PI3K/AKT/NF-κB signaling in MCAO/R rats. This study demonstrated that electroacupuncture reduces brain damage and inhibits inflammation in MCAO/R rats by modulating the PI3K/AKT/NF-κB signaling pathway and promoting the polarization of microglia from M1 to M2.

The study aimed to determine whether asymptomatic rats with cervical spinal cord compression (CSCC) experience more severe cervical spinal cord injury (SCI) compared with rats without CSCC under the same degree of minor trauma. Four weeks after the polyvinyl alcohol-polyacrylamide hydrogel was implanted into the C5 vertebral canal, asymptomatic rats were selected based on locomotor function score. Mild cervical SCI was subsequently established based on CSCC. The motor function, morphology, neuron loss, myelin destruction, nerve cell apoptosis, microglia activation, and neuroinflammation were evaluated after SCI. Under the same injury conditions, rats in the CSCC group exhibited more severe motor dysfunction compared with those without CSCC. Similarly, asymptomatic CSCC rats showed significant damage to spinal cord tissue, neurons, and myelin. Finally, compared with rats without CSCC, asymptomatic CSCC rats experienced increased nerve cell apoptosis, microglial activation, and neuroinflammation following the same SCI. In asymptomatic CSCC rats, the same degree of minor trauma resulted in more severe cervical SCI compared with rats without CSCC. This was evidenced by increased nerve cell apoptosis, microglial activation, neuron death, myelin destruction, and a strong neuroinflammatory response, leading to severe motor dysfunction.

Music has become an indispensable part of people's lives, frequently encountered in various contexts of daily living. Understanding the emotional significance of music is a crucial foundation for its use. This study employed the cross-modal affective priming paradigm, combined with event-related potential technology to investigate the influence of music elements on the emotional musical meaning from the perspective of interval structure. Two different forms of musical intervals (melodic interval and harmonic interval) and intervals with different varying degrees of consonance were used as priming stimuli and emotional words as target stimuli. The research results found that, compared to melodic intervals, participants responded faster and with higher accuracy under the harmonic interval condition, which also elicited a larger N400 component. Furthermore, the N400 amplitudes were smaller in four conditions compared to the dissonant-positive and consonant-positive conditions, and the consonant-negative condition elicited a significantly larger N400 amplitude than the dissonant-negative and partially consonant-negative conditions. This finding suggest that both interval type and consonance level influence emotional musical meaning, and interval structure plays a critical role in the understanding of emotional musical meaning.

The current study utilized functional near-infrared spectroscopy to examine the neural mechanisms underlying the effect of referential and emotional information on novel word learning. After learning the meaning of novel words in different sentences, participants were asked to complete a semantic consistency judgment task and a source judgment task. The behavioral data and neural data were recorded simultaneously. The results showed that: (1) referential information affected the novel word learning; (2) the interaction between referential and emotional information was significant; (3) these effects were associated with neural activities in the frontal and temporal lobe, mainly in the activation of the dorsolateral prefrontal cortex, the inferior frontal gyrus, the middle temporal gyrus, the superior temporal gyrus, and the premotor and supplementary motor cortex. The findings suggested that self-referential information could promote the novel word learning. Notably, referential and emotional information jointly affected the novel word learning in the frontal and temporal lobe, indicating the integrative contributions of both referential and emotional information to novel word learning.

We studied whether esculin (ES) has the effect of alleviating peripheral neuropathic pain (NP) in rat models of HIV glycoprotein 120 (gp120) together with zalcitabine (2',3'-dideoxycytidine; ddC) treatment and explored the possible mechanism of it. The rats pain behaviors were evaluated by observing the paw withdrawal threshold (PWT) and the paw withdrawal latency (PWL). The rats were divided into a control group, sham group, gp120 combined with a ddC treatment group (gp120& ddC group), gp120&ddC combined with ES treatment group (gp120&ddC+ES group), which ES was administered intragastrically, and gp120&ddC combined with short hair RNA of P2Y12 receptor (rP2Y12) treatment group (gp120&ddC+shP2Y12 group), which shRNA of rP2Y12 was injected intrathecally with a dose of 25 µg/20 µl for every rat, and a negative control plasmid was administered to the gp120&ddC+nc group. Western blotting was used to measure the protein expression levels of the rP2Y12, the nuclear factor of activated T-cells type c1 (NFATc1), phospho-NFATc1 and the C-C motif chemokine ligand 3 (CCL3) in the L4-L6 dorsal root ganglia (DRG). Real-time quantitative PCR (RT-qPCR) was used to test the mRNA expression level of the CCL3. Double-labeling immunofluorescence was used to identify the co-localization of the rP2Y12 with glial fibrillary acidic protein (GFAP) in DRG. Fluorescence imaging with calcium indicator fluo-3 AM (7.5 μM) was performed to observe the change of intracellular calcium concentration ([Ca2+]i). Molecular docking was performed to identify the interaction between rP2Y12 and the ligand ES. We found that accompanied by the attenuation of mechanical allodynia and thermal hyperalgesia, rP2Y12 expression in the gp120+ddC+ES group of rats was downregulated compared with the gp120+ddC ones, as was the coexpression of the rP2Y12 and GFAP of satellite glial cells (SGCs) in DRG, and the CCL3 mRNA levels and protein expression were both decreased. In addition, mechanistic studies have found that there is a docking pocket between ES and the rP2Y12 protein, which causes ES to decrease the [Ca2+]i, thus increasing the phosphorylation level of NFATc1. Taken together, the results suggest that ES can combine with the rP2Y12, inhibit DRG SGCs activation caused by gp120&ddC, reduce [Ca2+]i, and prevent the NFATc1-mediated gene transcription of CCL3, finally relieving NP in rats treated with gp120&ddC.

The prevalence of hyperuricemia (HUA) is climbing worldwide and persistent elevation of serum uric acid impairs cognitive function. This study aimed to explore the mechanisms of Artemisinin (Art) antagonizing cognitive disorder in HUA by suppressing pyroptosis. A mouse model of HUA was established by intraperitoneal injection of 300 mg/kg potassium oxonate (PO) in C57BL/6 mice for 14 days. The mice were simultaneously treated with Art, an agonist of pyroptosis Polyphyllin VI (PPVI), or glutamate receptor-interacting protein 1 (GRIP1) knockdown lentiviral plasmid. After treatment, serum uric acid, IL-6, and TNF-ɑ levels were examined, as well as hippocampal IL-1β and IL-18 levels, and the cognitive function of mice was assessed by the Morris water maze test. Pathological changes in the CA1 of the hippocampus were observed. Cleave-caspase-1, GSDMD-N, and GRIP1 protein level in the hippocampus was quantified by western blot. After PO induction, the escape latency and the time spent in the target quadrant increased in mice, cell arrangement in CA1 hippocampus was loose and disorganized, with obvious inflammatory infiltration and serious damage being observed, and the mouse hippocampus had elevated cleaved-caspase-1, GSDMD-N, IL-1β, and IL-18. Art treatment reduced pyroptosis in the hippocampus and improved cognitive disorder in HUA mice. Administration of PPVI aggravated cognitive disorder in Art-treated HUA mice, and Art improved cognitive dysfunction in HUA mice by inhibiting pyroptosis through upregulation of GRIP1. Art blunts pyroptosis in the hippocampus of HUA mice suffering from cognitive disorder by upregulating GRIP1.

Human visual working memory (VWM) is known to be capacity-limited, but the nature of this limit continues to be debated. Recent work has proposed that VWM is supported by a finite (~3) set of content-free pointers, acting as stand-ins for individual objects and binding features together. According to this proposal, the pointers do not represent features within themselves, but rather bind features represented elsewhere together. The current study set out to test if neural hallmarks resembling these content-free pointers can be observed with magnetoencephalography (MEG). Based on two VWM delay-match-to-sample experiments (N = 20 each) examining memory for simple and complex objects, we report a sustained response in MEG over right posterior cortex whose magnitude tracks the core hypothesized properties of this content-free pointer system: load-dependent, capacity-limited, and content-free. These results provide novel evidence for a finite set of content-free pointers underlying VWM.

As exosome therapy is a promising treatment in neurological disorders including epilepsy, the present study aimed to evaluate the effects of exosomes obtained from human adipose-derived stem cells (ADSCs) on pentylenetetrazol (PTZ) model of epilepsy in mice. Thirty adult mice were divided into PTZ, diazepam + PTZ, and exosome (5, 10, and 15 µg) + PTZ groups. The exosomes were administered intranasally 30 min before PTZ injection. The seizure latency, tonic-clonic onset, seizure duration, and mortality protection rate were monitored. Also, the level of hippocampal malondialdehyde (MDA), the oxidative stress marker, was evaluated. Exosomes in 5 and 15 µg concentration significantly increased seizure latency. Only 15 µg of exosomes induced a considerable delay in tonic-clonic onset. Seizure duration was significantly attenuated in the 5 µg exosome group. In addition, the 5-µg exosome indicated the highest mortality protection rate. Furthermore, the MDA level was significantly reduced in all animals treated by exosomes. Exosomes obtained from human ADSCs could alleviate epileptogenesis induced by PTZ maybe through reducing hippocampal oxidative stress.

The amygdala responds to emotional stimuli but habituates at repeated presentation. Much less is known about time-on-task effects during exposure to emotional stimuli in the cortex. Here, we identified the neural substrates that show habituation or cortical decreased activity in a task of repeated passive exposure to faces with negative emotional expressions. We found that in the amygdala, habituation selectively involved the central nucleus and extended posteriorly in the hippocampal-amygdaloid region, consistently with reduced motivational and attentional effects of repeated stimulation. In the cortex, decreases in activity with time on task involved a network including the temporoparietal junction, the postsplenial region, and the ventromedial prefrontal cortex, mostly located at the transition from task activations to deactivations. These effects were analogous to those reported as encoding of social cognition information, suggesting a role in developing task-based representations of input content.