Neuroreport最新文献

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.

Background: We recently demonstrated that systemically transplanted astrocytic mitochondria enter the intracerebral hemorrhage (ICH)-affected brain, where they protect the neurons by mitigating oxidative damage via upregulation of the manganese superoxide dismutase (Mn-SOD), ultimately contributing to functional recovery after ICH in mice. Although our previous study clearly demonstrated the beneficial effects of mitochondria within the brain, the effect of transferred mitochondria on the peripheral system was not yet studied. Thus, here, we studied the impact of astrocytic mitochondria transfer on post-ICH recovery and modulation of systemic immune responses.

Methods: We used the autologous blood injection model for the mouse ICH surgery. Mice subjected to ICH received astrocytic mitochondria intravenously at 1 h, 7, and 14 days post-ICH onset, and the splenic immune responses of these mice were analyzed at 21 days. An ICH-like injury was induced in vitro using primary cultured neurons treated with recombinant interleukin-10, and cell viability, reactive oxygen species levels, and gene expressions were analyzed.

Results: We demonstrate that systemic transplantation of astrocytic mitochondria increases the population of splenic B cells, production of interleukin-10 by B cells, and plasma interleukin-10 levels in mice after ICH. Furthermore, in the ICH-like injury in vitro , exogenous interleukin-10 (to model spleen-mediated interleukin-10 increase) upregulated Mn-SOD expression in the cultured neurons and promoted neuronal survival and neuroplasticity-related gene expressions, suggesting interleukin-10 role in cytoprotection and repair/recovery under ICH-like condition.

Conclusions: Thus, systemic transfer of astrocytic mitochondria modulates post-ICH peripheral immune responses, which may participate in functional recovery.

Introduction: Excessive neuroinflammation resulting from chronic alcohol intake is an important risk factor for central nervous system injury. The aim of this study was to investigate the effect of kaempferol (KAE) on alcohol-induced neural injury and its underlying mechanism.

Methods: C57BL/6 N mice were employed to develop a binge-on-chronic alcohol exposure model, with different doses of KAE as an interventional drug for 6 weeks. Neuronal damage and microglial activation in the brain, as well as colonic tissue damage and serum lipopolysaccharide (LPS) concentrations, were systematically assessed. Additionally, Caco-2 cells were exposed to alcohol to induce intestinal epithelial injury in vitro.

Results: Chronic alcohol exposure let to significant neuronal damage in the cortex and hippocampus of mice. KAE treatment effectively attenuated microglial activation and reduced neuronal damage in the brains of alcohol-exposed mice. Analysis of colonic tissues revealed that KAE administration inhibited miRNA-122a expression, alleviated pathological damage, and enhanced occludin expression, thereby significantly lowing serum LPS concentrations in alcohol-fed mice. In vitro, KAE markedly decreased miRNA-122a expression and enhanced occludin levels in Caco-2 cells treated with alcohol. Furthermore, overexpression of miRNA-122a was found to diminish occludin protein production in Caco-2 cells, which was significantly counteracted by KAE treatment.

Conclusion: KAE treatment enhanced intestinal barrier function to alleviate neuronal damage caused by microglial activation mediated by gut-derived LPS under alcohol expose. This effect of KAE was involved in the enhance of intestinal occludin expression by inhibiting the expression of miRNA-122a. This suggested that KAE had the potential to prevent alcohol-induced neurological damage.

Objective: Perioperative neurocognitive disorder (PND) is a significant complication affecting elderly patients after surgery, with limited effective interventions to improve its prognosis yet. We have found that decreased serum adiponectin (APN) and increased cerebrospinal fluid (CSF) lactate are involved in the pathophysiological process of PND in elderly patients. APN is known for its anti-insulin resistance property. In this study, we further explored the regulatory effects of APN on cerebral glucose metabolism in PND rats.

Methods: Twelve-month-old male Sprague-Dawley rats were divided into 3 groups: the sham, PND (splenectomy) and PND+APN (50 mg/kg/day intragastrically) groups. ELISA, quantitative PCR and colorimetric analysis were conducted to analyze tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), pyruvate and lactate in serum, CSF and hippocampus. Open field and Morris water maze (MWM) tests were used to detect hippocampus-dependent cognitive function. Western blot and flow cytometry were conducted to detect neuronal apoptosis in primary hippocampal neurons.

Results: In vivo, peripheral APN administration reversed surgery-induced reductions in serum APN expression and elevated levels of cerebral lactate, the ratio of lactate/pyruvate, TNF-α and IL-1β, thereby improving cognitive performance in MWM and Open Field tests. In vitro, APN at concentrations of 2 and 10 ng/ml dose-dependently reduced lipopolysaccharide-induced caspase 3 expression and p38 phosphorylation in neurons, inhibiting apoptosis.

Conclusions: Cerebral hypometabolism is one of the pathogenic mechanisms of PND. APN shows its effects on regulating glucose metabolism to inhibit neuroinflammation and neuronal apoptosis in PND. And the underlying mechanism of APN should be investigated further.

Objective: Early brain injury (EBI) is the main cause of poor outcomes in patients with subarachnoid hemorrhage (SAH). Tetrandrine (Tet) is the root of Stephania tetrandra S Moore extract that has been shown to promote neuronal survival and regulate a variety of signaling pathways; however, the mechanism through which it exerts neuroprotective effects in patients with SAH is unknown. This investigation was to examine Tet's effect on EBI in SAH rats.

Basic methods: We divided the rats into four groups. The effects of Tet treatment on the pathological changes of neurons in rat brains were evaluated, as well as autophagy-related and signaling pathway proteins.

Main results: We found that Tet had a neuroprotective effect on EBI after SAH, as evidenced by the fact that Tet ameliorated SAH-mediated neurologic impairment and neuronal morphological damage and reduced brain water content, neuronal apoptosis rate, and neuronal cell loss. Tet decreased the LC3II/LC3I ratio, elevated P62 protein expression, and inhibited autophagosome production after SAH. Tet may have increased sirtuin 3 (SIRT3) expression, decreased adenosine 5-monophosphate-activated protein kinase (AMPK) phosphorylation, and increased phosphor-mammalian target of rapamycin (mTOR) levels, all of which may have occurred particularly via SIRT3/AMPK/mTOR signaling pathway activation; However, this trend can be reversed by 3-(1H-1,2,3-triazol-4-yl) pyridine (SIRT3 inhibitors).

Conclusions: Tet exerts neuroprotective effects by inhibiting autophagy, this may be associated with SIRT3's inhibitory effect on the AMPK/mTOR signaling pathway. This inhibition could function as a potential mechanism for the neuroprotective effects observed in patients suffering from SAH.

Background: Humans live surrounded by many sounds and have the ability to filter out various background sounds. It involves stream segregation and temporal integration. When the reference frequency is set to 3000 Hz, stream segregation will precede temporal integration when the frequency difference is 1000 Hz or larger; however, there is no report that examines whether the threshold of frequency difference at which stream segregation occurs before temporal integration is similar to different base tones.

Methods: We created 10 blocks of tone sequences in which high tones and low tones were alternated with a constant stimulus onset asynchrony of 120 ms. In the first group (group A), the frequency of base tones was fixed at 3000 Hz. In the second group (group B), the frequency of base tones was fixed at 2000 Hz. The frequency of pair tones was set at 3000, 2750, 2500, 2250, and 2000 Hz in each block, respectively presented with six blocks of alternating high tones and low tones.

Results: In group A, the mean voltage in response to omission was significantly lower than the mean voltage in response to opposite tones except in the fifth block. On the other hand, in group B, the mean voltage in response to omission was significantly lower than the mean voltage in response to opposite tones in all blocks.

Conclusions: Our results indicated that whether a temporal window of integration or stream segregation is preferred depends on the base tone's Hz.