Neuroreport最新文献

Background: The incidence of postoperative cognitive dysfunction (POCD) in elderly patients is high and related to an increased postoperative mortality rate. Magnolol has the potential to improve cognitive function, but its therapeutic effects and mechanisms of action on POCD remain unclear.

Methods: An aged mouse model of POCD was constructed using sevoflurane anesthesia and abdominal exploratory surgery. Magnolol was administered via intragastric gavage at doses of 10 or 20 mg/kg daily, starting 1 week before surgery. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown mice were used to investigate the role of the Nrf2/antioxidant response element (ARE) pathway in the therapeutic effects of magnolol on POCD.

Results: In POCD mice, magnolol treatment significantly reduced the escape latency, increased crossing numbers in the platform quadrant and target quadrant dwell time, and enhanced the novel object recognition index. Meanwhile, under the action of magnolol, the morphology of hippocampal neurons was protected, the rate of cell apoptosis was reduced, and the expression of antiapoptotic protein B-cell lymphoma 2 was upregulated. Magnolol also reduced the levels of monocyte chemoattractant protein-1, tumor necrosis factor-alpha, interleukin-1β, and reactive oxygen species, while increasing the levels of superoxide dismutase, glutathione, and glutathione peroxidase. In addition, magnolol activated proteins related to the Nrf2/ARE pathway. Notably, silencing Nrf2 weakened the effect of magnolol on improving cognitive function in POCD mice.

Conclusion: Magnolol may effectively improve POCD in aged mice by activating the Nrf2/ARE pathway.

Background: Previous studies have shown that two core subregions of the prefrontal cortex - the dorsolateral prefrontal cortex (DLPFC) and the inferior frontal gyrus (IFG) - are both closely related to cognitive control in creativity; however, the similarities and differences in their cognitive control mechanisms during creativity remain to be further clarified.

Methods: This study employed a within-subject design, using transcranial direct current stimulation to manipulate the activity of left DLPFC and IFG separately. Participants completed divergent and convergent thinking tasks under three conditions: anodal stimulation of the left DLPFC, cathodal stimulation of the left IFG, and sham stimulation. The novelty and appropriateness of generated answers during idea generation, as well as those selected during idea selection, were compared across conditions.

Results: (a) Anodal stimulation of the left DLPFC significantly enhanced the novelty of answers generated during idea generation in both the alternate uses task (AUT) and the product improvement task and helped to select the more appropriate answer during idea selection in AUT. (b) Cathodal stimulation of the left IFG significantly improved the novelty of ideas generated in the AUT but had no significant effect on performance during idea selection.

Conclusion: The cognitive control mechanisms of the left DLPFC and IFG differ during the creative process. Anodal stimulation of the left DLPFC enhances goal-directed cognitive control, thereby promoting creativity, whereas cathodal stimulation of the left IFG facilitates the generation of creative ideas by releasing inhibitory control over semantic retrieval.

Objective: This study aimed to investigate the role of alectinib in a neonatal mouse model of germinal matrix hemorrhage (GMH).

Methods: We induced GMH in postpartum day 5 mouse pups by injecting collagenase into the germinal matrix. Alectinib was administered intraperitoneally after GMH induction. Western blot, immunofluorescence staining, and quantitative PCR were performed to explore the effects of alectinib on oxidative stress, microglial number, proinflammatory cytokines expression, blood-brain barrier (BBB) damage, and cortical neuron loss. Cresyl violet and Prussian blue staining were used to detect the ventricular size, cerebral cortical atrophy, and hemorrhage burden. Novel object recognition and rotarod tests were used to determine the neurological function.

Results: We found that anaplastic lymphoma kinase (ALK) was upregulated in the perihematomal areas following GMH and was presented in endothelial cells. Treatment with alectinib resulted in a reduction in oxidative stress, as shown by decreasing generation of reactive oxygen species, lipid peroxidation, and oxidative DNA at 3 days after GMH. Alectinib also attenuated the number of microglia, levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α, loss of BBB integrity ZO-1 and claudin-5, and disruption of BBB. These effects of alectinib were accompanied by reduced hemorrhage burden, cortical neuron loss and cerebral cortical atrophy, and improved motor coordination, cognitive and memory impairments at 23 days after GMH.

Conclusion: Our data revealed that alectinib reduced oxidative stress, microglia number, and BBB permeability, thereby alleviating secondary brain injury in GMH. Therapies that inhibit ALK signaling may confer neuroprotection against GHM.

Objective: Menthol is widely used as a cooling agent and an adjunctive analgesic to relieve various painful conditions, such as migraine. As menthol acts as an agonist for the thermosensitive ion channel transient receptor potential melastatin 8 (TRPM8), other ion channels, such as voltage-gated Na + channels, are also involved in the antinociceptive effect of menthol. In this study, we explored the effect of menthol on tetrodotoxin-resistant (TTX-R) Na + channels in nociceptive sensory neurons.

Methods: TTX-R Na + current (I Na ) was recorded from acutely isolated rat dural afferent neurons identified with the fluorescent dye DiI using a whole-cell patch-clamp technique.

Results: Under a voltage-clamp condition, menthol potently decreased the amplitude of the persistent TTX-R Na + current (I Na ) in a concentration-dependent manner, with a minor effect on the transient current. The inhibition of persistent TTX-R I Na by menthol was not affected by the TRPM8 antagonist. Menthol (300 μM) (1) shifted the steady-state fast inactivation relationship to hyperpolarizing ranges without affecting the voltage-activation relationship, (2) accelerated the onset of inactivation, and (3) retarded the recovery from the inactivation of TTX-R Na + channels. Under the current clamp condition, menthol (300 μM) decreased the threshold for action potential generation but reduced the number of action potentials elicited by strong depolarizing current stimuli.

Conclusion: The results of this study suggest that menthol exerts an analgesic effect by preferentially inhibiting persistent TTX-R I Na and modulating the inactivation and recovery kinetics of TTX-R Na + channels.

Background: Although previous neuroimaging studies have revealed alterations in the static brain networks of patients with high myopia, little is known about changes in their dynamic brain networks, particularly regarding directional connectivity within these networks, warranting further investigation.

Methods: In this study, resting-state functional MRI was conducted on 82 confirmed patients with high myopia and 59 healthy controls. Employing dynamic Granger causality analysis, sliding time windows, and K-means clustering, we assessed dynamic alterations in effective connectivity within the brain's functional networks in patients with high myopia.

Results: Patients with high myopia show significantly enhanced dynamic effective connectivity (dEC) between the visual network and the default mode network (DMN) compared with healthy controls. Furthermore, aberrant connectivity is detected between the visual network and the limbic network. In addition, intravisual network dEC is markedly increased. In state 1, the frequency differed significantly between the two groups, with high myopia patients showing a markedly higher frequency than healthy controls.

Conclusion: This study found that patients with high myopia exhibit significantly altered patterns of dEC, especially increased connectivity between the visual network, the DMN, and the limbic network. Furthermore, significantly increased intranetwork dEC within the visual network indicates enhanced internal visual information processing. These findings offer new insights into the neural mechanisms of high myopia and suggest that long-term visual impairment may trigger functional reorganization in both visual and nonvisual brain networks.

Objective: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, T helper 17 (Th17) cells play a key role in its pathogenesis. T cells constitute an important subtype of cells in the immune system and play diverse roles in fighting infections, targeting tumors, and regulating autoimmune responses. Under different conditions, T cells can differentiate into various specialized types each with unique functions in the immune system. Among them, Th17 cells are known to exhibit both pathogenic and nonpathogenic functions. Previous studies have demonstrated that pathogenic Th17 cells play a pivotal role in the pathogenesis of human MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Recent data have shown that autocrine activin-A induces pathogenic Th17 cells, which promote neuroinflammation. However, the upstream regulatory mechanisms remain unclear.

Methods: We found that both interleukin (IL)-1β and IL-23 induce activin-A production through the myeloid differentiation primary response protein 88 (MyD88)-transforming growth factor-β-activated kinase 1 (TAK1)-c-Jun N-terminal kinase (JNK) axis under inflammatory conditions. Inhibition of MyD88 function significantly suppressed activin-A expression, which markedly impaired IL-17 production from T cells and ameliorated the disease in the EAE model.

Results: Activation of the MyD88-JNK pathway by IL-1β and IL-23 promotes activin-A production in pathogenic Th17 cells and exacerbates EAE.

Conclusions: MyD88 signaling in T cells may be an attractive clinical target for anti-inflammatory therapies for diseases of the central nervous system.

This study aimed to investigate phase-based functional connectivity during decision-making and outcome evaluation in the stag hunt game using electroencephalography (EEG). Thirty-five healthy participants completed a repeated stag hunt task while EEG was recorded. Functional connectivity was assessed using the weighted phase lag index. Paired-sample t tests were conducted to compare connectivity strength between (a) cooperative vs. defective choices during the decision phase (200-300 ms, theta band) and (b) gain vs. loss feedback during the outcome phase (200-500 ms, delta band). During the decision phase, theta-band connectivity was significantly higher for defect choices in frontocentral and parietal electrode pairs (e.g. FC2-C4, CP4-FC2). During the outcome phase, gain feedback elicited stronger delta-band connectivity across frontoparietal and fronto-occipital networks (e.g. AF8-O1/O2, CP2-Cz, and PO7-AF8). These findings reveal distinct oscillatory connectivity patterns associated with social decision-making and reward evaluation. Defection involves enhanced frontoparietal theta synchronization linked to cognitive control, whereas gain feedback engages broader delta networks related to reward processing. This study provides novel insights into the neural dynamics of cooperation and defection in social contexts.

Background: Parkinson's disease (PD) is a chronic neurodegenerative disorder marked by motor symptoms and nonmotor complications, notably cognitive impairment, which severely impairs patients' quality of life. While circadian disruption (CD) correlates with cognitive decline in PD, it remains unclear whether CD is merely secondary to motor symptoms or directly contributes to cognitive dysfunction. The objective of this study was to investigate whether chronic CD exacerbates cognitive decline in PD.

Basic methods: Male mice were subjected to the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD and divided into groups with or without chronic exposure to CD. Observational assessments of cognitive deficits were performed alongside analytical measurements of tyrosine hydroxylase (TH) content in the striatum, α-synuclein deposition levels, and neuroinflammatory responses in the hippocampus.

Main results: MPTP-treated mice exposed to CD exhibited significantly more severe cognitive deficits compared to MPTP-treated controls without CD. These deficits correlated with pronounced reductions in striatal TH content, elevated α-synuclein accumulation, and intensified neuroinflammatory activity in the hippocampal region. The observed changes demonstrated CD-induced exacerbation of pathological hallmarks.

Conclusions: Chronic CD directly aggravates MPTP-driven neuroinflammatory processes and α-synuclein pathology in the hippocampus, leading to accelerated cognitive deterioration. These findings substantiate CD as an environmental risk factor for cognitive decline in PD progression, independent of motor symptom sequelae. The study provides mechanistic insights into CD's contributory role in PD-related cognitive impairment.

Background: Thyroid-associated ophthalmopathy (TAO), characterized by eyelid retraction, proptosis, extraocular muscle hypertrophy, and pathological elevation of intraorbital pressure, represents a potentially devastating autoimmune disorder affecting both ocular structure and visual function. Emerging evidence demonstrates significant neurophysiological correlations in TAO pathogenesis, manifesting cerebral hemispheric specialization and cooperation; however, conventional methodologies failed to account for inherent anatomical asymmetries between cerebral hemispheres. Therefore, the present study used a new data analysis method to systematically interrogate hemispheric specialization and cooperation in TAO, while concurrently exploring its multi-omics correlations with transcriptomic signatures and neuromodulatory receptors/transporters.

Methods: A total of 32 patients with TAO and demographically matched healthy controls underwent high-resolution resting-state functional MRI. Whole-brain connectome matrices profiling autonomy index-functional homotope (CFH) interactions were generated to quantitatively characterize lateralized functional decoupling and transhemispheric coordination deficits in TAO. Voxel-wise aberrations in autonomy index/CFH metrics underwent multimodal correlation mapping with whole-transcriptome expression profiles and neurotransmitter receptor/transporter density atlases.

Results: Patients with TAO had higher abnormal autonomy index expression in the left inferior temporal gyrus; CFH values were reduced in the left cuneus, right cuneus, left precuneus, right precuneus, and left superior parietal. Enrichment analysis of genes associated with abnormal autonomy index and CFH values, respectively, revealed that these genes were mainly involved in synaptic development and regulation. Finally, in the density correlation analysis of abnormal CFH values with neurotransmitter receptors/transporters, significant correlations were found for 5-hydroxytryptamine (5-HT) 1A R, 5-HT 2A R, CB 1 R, GABA A R, M 1 R, and mGlu 5 R.

Conclusion: This multimodal investigation yields novel neurobiological insights into hemispheric dysregulation patterns in TAO, while elucidating the pathophysiological continuum of this complex disorder.

Objectives: Arginine vasopressin (AVP) is synthesized in the magnocellular supraoptic nucleus and paraventricular nuclei of the hypothalamus, where AVP neurons function under a consistently high demand for AVP production. AVP neurons are subject to endoplasmic reticulum (ER) stress even under basal conditions, and this ER stress is further exacerbated when AVP production increases due to dehydration. Reticulon (RTN) is essential for ER formation and stabilization and plays a critical role in membrane morphogenesis within the ER. This study aimed to investigate the expression of RTN family members in hypothalamic AVP neurons.

Methods: Fluorescence immunohistochemistry and in-situ hybridization were employed to examine the expression of RTN family members in hypothalamic AVP neurons of adult male mice. Water deprivation and treatment with a chemical chaperone 4-phenylbutyric acid were used to increase and decrease the ER stress of AVP neurons, respectively.

Results: Among the RTN family members, only RTN4 was found to be expressed in hypothalamic AVP neurons. RTN4 was colocalized with ER organelle markers, including immunoglobulin heavy chain binding protein and calnexin. Furthermore, RTN4 expression increased during ER stress induced by water deprivation. On the other hand, increased RTN4 expression by water deprivation was attenuated by 4-phenylbutyric acid treatment.

Conclusions: Our results suggest that RTN4 expression in AVP neurons is closely associated with ER stress caused by increased protein production in neuroendocrine cells.