Journal of integrative neuroscience最新文献

Background: The solute carrier (SLC) superfamily, which transports solutes across biological membranes, includes four members (SLC2A1, SLC6A1, SLC9A64, and SLC35A2) that have been linked to epilepsy. This study sought to examine the DNA methylation patterns near the promoters of these genes in temporal lobe epilepsy (TLE), as DNA methylation is a crucial epigenetic modification that can impact gene expression.

Methods: The study comprised 38 individuals with TLE and 38 healthy controls. Methylation experiments were performed using peripheral blood, while demethylation experiments were carried out using SH-SY5Y cells with the DNA methylation inhibitor decitabine.

Results: A significant difference was observed in the DNA methylation rate of SLC6A1 between TLE patients and controls, with TLE patients showing a lower rate (4.81% vs. 5.77%, p = 0.0000), which remained significant even after Bonferroni correction (p = 0.0000). Based on the hypomethylated SLC6A1 in TLE, a predictive model was established that showed promise in distinguishing and calibrating TLE. In the TLE group, there were differences in DNA methylation rates of SLC6A1 between the young patients and the older controls (4.42% vs. 5.22%, p = 0.0004). A similar trend (p = 0.0436) was noted after adjusting for sex, age at onset, and drug response. In addition, the study found that DNA methylation had a silencing impact on the expression of the SLC6A1 gene in SH-SY5Y cells, which were treated with decitabine at a set dose gradient.

Conclusions: The evidence suggests that lower methylation of SLC6A1 may stimulate transcription in TLE, however, further investigation is necessary to confirm the exact mechanism.

Objective: To explore the relationship between YKL-40 level, telomere length, and different subtypes of insomnia disorder.

Methods: A total of 145 individuals suffering from insomnia were enrolled and divided into four groups according to the insomniac subtypes: difficulty initiating sleep, early morning awakening, difficulty maintaining sleep, and mixed symptoms. Eighty healthy controls were also collected at the same time. Peripheral leukocyte genomic DNA was extracted, relative telomere lengths were measured using the real-time quantitative polymerase chain reaction method, and YKL-40 levels were determined using enzyme-linked immunoassay. Logistic regression modeling was used to analyze the correlation between different insomnia subtypes, YKL-40 level, and telomere length.

Results: People with telomere lengths in the lowest tertile were more likely to have trouble falling asleep (odds ratio (OR) 2.13, 95% confidence interval (CI) 1.22-3.63; p = 0.03) and had a higher frequency of mixed symptoms (OR 1.49, 95% CI 1.30-2.81; p = 0.04). People in the highest tertile of YKL-40 level had an increased chance of waking up early (OR 2.98, 95% CI 1.54-5.33; p = 0.01) and more mixed symptoms (OR 1.47, 95% CI 1.22-2.79; p = 0.02). Furthermore, using receiver operating characteristic curve analysis, the area under the curve of YKL-40 level and telomere length was 0.806 and 0.746, respectively.

Conclusions: Telomere length in patients with difficulty initiating sleep and mixed symptoms was significantly shortened and the level of YKL-40 in people who have early morning awakening and mixed symptoms was significantly increased. Our findings provide the first evidence that leukocyte telomere length and YKL-40 level are individually linked to mixed symptoms.

Background: Schizophrenia is a complex and disabling mental disorder that represents one of the most important challenges for neuroimaging research. There were many attempts to understand these basic mechanisms behind the disorder, yet we know very little. By employing machine learning techniques with age-matched samples from the auditory oddball task using multi-site functional magnetic resonance imaging (fMRI) data, this study aims to address these challenges.

Methods: The study employed a three-stage model to gain a better understanding of the neurobiology underlying schizophrenia and techniques that could be applied for diagnosis. At first, we constructed four-level hierarchical sets from each fMRI volume of 34 schizophrenia patients (SZ) and healthy controls (HC) individually in terms of hemisphere, gyrus, lobes, and Brodmann areas. Second, we employed statistical methods, namely, t-tests and Pearson's correlation, to assess the group differences in cortical activation. Finally, we assessed the predictive power of the brain regions for machine learning algorithms using K-nearest Neighbor (KNN), Naive Bayes, Decision Tree (DT), Random Forest (RF), Support Vector Machines (SVMs), and Extreme Learning Machine (ELM).

Results: Our investigation depicts promising results, obtaining an accuracy of up to 84% when applying Pearson's correlation-selected features at lobes and Brodmann region level (81% for Gyrus), as well as Hemispheres involving different stages. Thus, the results of our study were consistent with previous studies that have revealed some functional abnormalities in several brain regions. We also discovered the involvement of other brain regions which were never sufficiently studied in previous literature, such as the posterior lobe (posterior cerebellum), Pyramis, and Brodmann Area 34.

Conclusions: We present a unique and comprehensive approach to investigating the neurological basis of schizophrenia in this study. By bridging the gap between neuroimaging and computable analysis, we aim to improve diagnostic accuracy in patients with schizophrenia and identify potential prognostic markers for disease progression.

Background: Beneficial effects of whole-body vibration (WBV) on brain and musculoskeletal health in mice have been demonstrated, but underlying mechanisms remain relatively unrevealed. WBV improves attention and memory performance in mice, putatively through stimulation of the cholinergic system. Here, we investigated the effects of WBV on the septo-hippocampal cholinergic system.

Methods: Young C57BL/6 mice (8 weeks old) were subjected to 10 min WBV/day (mechanical vibration: 30 Hz; ~0.1-μm peak-to-peak displacement), 5X/week for 5 weeks. In Experiment 1, choline acetyltransferase (ChAT)-immunoreactivity in the septum and hippocampus was analyzed either 2 or 24 h after the last WBV session. Pseudo-WBV-treated mice (same handling procedure as WBV, but no vibrations) served as controls. In Experiment 2, the longitudinal profile of ChAT-immunoreactivity was analyzed in the hippocampus after 1, 2, 3, 4, or 5 weeks of WBV. In addition, synaptophysin immunostaining was performed at either 2 and 5 weeks of WBV. Mice housed 1/cage during the entire experiment served as controls. The balance-beam test was used to monitor the functional impact of WBV. In Experiment 3, a Y-maze reference-memory test was performed after 5 weeks of WBV to obtain a functional cognitive outcome measure of WBV. Pseudo-WBV treated mice served as controls.

Results: In Experiment 1, ChAT-immunoreactivity was significantly enhanced after the last WBV session of the 5-week period. This was found in the septum, Cornu Ammonis 1 (CA1), CA3, and dentate gyrus, and was dependent on layer and time-point (2 or 24 h). Experiment 2 revealed that, ChAT-immunoreactivity was lower after 2 weeks of WBV, whereas it was significantly higher after 5 weeks (similar to in Experiment 1). Immunostaining for synaptophysin, a marker for synaptic density, was also significantly higher after 5 weeks of WBV, but not significantly lower after 2 weeks, as was ChAT. WBV-treated groups performed significantly better than did controls on the balance beam from week 3 onwards. Experiment 3 showed that WBV-treated mice had better spatial-reference memory performance in the Y-maze test than did pseudo-WBV controls.

Conclusions: Our results indicate that WBV stimulates the septo-hippocampal cholinergic system in a gradual and dynamic way that may contribute to improved spatial-memory performance. This finding suggests that WBV, by upregulation of the septo-hippocampal cholinergic system, may be considered a valuable therapeutic strategy to enhance brain functions in aging, neurodegenerative, and other brain diseases.

Background: The abnormal aggregation of α-synuclein (α-syn) in the substantia nigra pars compacta (SNpc) region of the brain is characteristic of Parkinson's disease (PD), leading to the selective demise of neurons. Modifications in the post-translational processing of α-syn, phosphorylation at Ser¹²⁹ in particular, are implicated in α-syn aggregation and are considered key hallmarks of PD. Furthermore, dysregulated Wnt/β-catenin signaling, influenced by glycogen synthase kinase-3 beta (GSK-3β), is implicated in PD pathogenesis. Inhibition of GSK-3β holds promise in promoting neuroprotection by enhancing the Wnt/β-catenin pathway.

Methods: In our previous study utilizing 1-methyl-4-phenylpyridinium (MPP⁺)-administered differentiated SH-SY5Y cells and a PD mouse model, we explored Vanillin's neuroprotective properties and related mechanisms against neuronal loss induced by MPP⁺/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. In the current study, we elucidated the mitigating effects of Vanillin on motor impairments, P-Ser¹²⁹-α-syn expression, Wnt/β-catenin signaling, and autophagic neuron death induced by MPTP in a mouse model of PD by performing motor function tests, western blot analysis and immunostaining.

Results: Our results show that Vanillin effectively modulated the motor dysfunctions, GSK-3β expression, and activity, activated the Wnt/β-catenin signaling, and reduced autophagic neuronal demise in the MPTP-lesioned mice, highlighting its neuroprotective effects.

Conclusions: These findings underscore the complex interplay between α-syn pathology, GSK-3β, Wnt/β-catenin signaling, and autophagic-cell death in PD pathogenesis. Targeting these pathways, particularly with Vanillin, can be a promising therapeutic strategy for restoring dopaminergic (DA-ergic) neuronal homeostasis and slowing the progression of PD. Further research is crucial to resolving existing disputes and translating these discoveries into effective therapeutic interventions for PD patients.

Background: Stroke remains a leading cause of disability globally and movement impairment is the most common complication in stroke patients. Resting-state electroencephalography (EEG) microstate analysis is a non-invasive approach of whole-brain imaging based on the spatiotemporal pattern of the entire cerebral cortex. The present study aims to investigate microstate alterations in stroke patients.

Methods: Resting-state EEG data collected from 24 stroke patients and 19 healthy controls matched by age and gender were subjected to microstate analysis. For four classic microstates labeled as class A, B, C and D, their temporal characteristics (duration, occurrence and coverage) and transition probabilities (TP) were extracted and compared between the two groups. Furthermore, we explored their correlations with clinical outcomes including the Fugl-Meyer assessment (FMA) and the action research arm test (ARAT) scores in stroke patients. Finally, we analyzed the relationship between the temporal characteristics and spectral power in frequency bands. False discovery rate (FDR) method was applied for correction of multiple comparisons.

Results: Microstate analysis revealed that the stroke group had lower occurrence of microstate A which was regarded as the sensorimotor network (SMN) compared with the control group (p = 0.003, adjusted p = 0.036, t = -2.959). The TP from microstate A to microstate D had a significant positive correlation with the Fugl-Meyer assessment of lower extremity (FMA-LE) scores (p = 0.049, r = 0.406), but this finding did not survive FDR adjustment (adjusted p = 0.432). Additionally, the occurrence and the coverage of microstate B were negatively correlated with the power of delta band in the stroke group, which did not pass adjustment (p = 0.033, adjusted p = 0.790, r = -0.436; p = 0.026, adjusted p = 0.790, r = -0.454, respectively).

Conclusions: Our results confirm the abnormal temporal dynamics of brain activity in stroke patients. The study provides further electrophysiological evidence for understanding the mechanism of brain motor functional reorganization after stroke.

Background: Sleep deprivation (SD) can impair an individual's alertness, which is the basis of attention and the mechanism behind continuous information processing. However, research concerning the effects of total sleep deprivation (TSD) on alertness networks is inadequate. In this study, we investigate the cognitive neural mechanism of alertness processing after TSD.

Methods: Twenty-four college students volunteered to participate in the study. The resting-state electroencephalogram (EEG) data were collected under two conditions (rested wakefulness [RW], and TSD). We employed isolated effective coherence (iCoh) analysis and functional independent component analysis (fICA) to explore the effects of TSD on participants' alertness network.

Results: This study found the existence of two types of effective connectivity after TSD, as demonstrated by iCoh: from the left cuneus to the right middle frontal gyrus in the β3 and γ bands, and from the left angular gyrus to the left insula in the δ, θ, α, β1, β3, and γ bands. Furthermore, Pearson correlation analysis showed that increased effective connectivity between all the bands had a positive correlation with increases in the response time in the psychomotor vigilance task (PVT). Finally, fICA revealed that the neural oscillations of the cuneus in the α2 bands increased, and of the angular gyrus in the α and β1 bands decreased in TSD.

Conclusions: TSD impairs the alertness function among individuals. Increased effective connectivity from the cuneus to the middle frontal gyrus may represent overloads on the alertness network, resulting in participants strengthening top-down control of the attention system. Moreover, enhanced effective connectivity from the angular gyrus to the insula may indicate a special perception strategy in which individuals focus on salient and crucial environmental information while ignoring inessential stimuli to reduce the heavy burden on the alertness network.

Clinical trial registration: No: ChiCTR2400088448. Registered 19 August 2024, https://www.chictr.org.cn.

Spinal cord injury (SCI) is a severe central nervous system disorder with no currently available effective treatment. Microglia are immune cells in the central nervous system that play crucial roles in the SCI occurrence, development, and recovery stages. They exhibit dynamic polarization over time and can switch between classical activation (M1) and alternative activation (M2) phenotypes to respond to environmental stimuli. The M1 phenotype is involved in initiating and sustaining inflammatory responses, while the M2 phenotype exerts anti-inflammatory effects and promotes tissue repair in damaged areas. Inhibiting M1 polarization and promoting M2 polarization have become hotspots in regulating neuroinflammation and treating SCI. This article provides a comprehensive review centered on modulating microglial polarization phenotypes for SCI treatment.

Background: Identifying white matter (WM) microstructural similarities and differences between major depressive disorder (MDD) and bipolar disorder (BD) is an important way to understand the potential neuropathological mechanism in emotional disorders. Numerous diffusion tensor imaging (DTI) studies over recent decades have confirmed the presence of WM anomalies in these two affective disorders, but the results were inconsistent. This study aimed to determine the statistical consistency of DTI findings for BD and MDD by using the coordinate-based meta-analysis (CBMA) approach.

Methods: We performed a systematic search of tract-based spatial statistics (TBSS) studies comparing MDD or BD with healthy controls (HC) as of June 30, 2024. The seed-based d-mapping (SDM) was applied to investigate fractional anisotropy (FA) changes. Meta-regression was then used to analyze the potential correlations between demographics and neuroimaging alterations.

Results: Regional FA reductions in the body of the corpus callosum (CC) were identified in both of these two diseases. Besides, MDD patients also exhibited decreased FA in the genu and splenium of the CC, as well as the left anterior thalamic projections (ATP), while BD patients showed FA reduction in the left median network, and cingulum in addition to the CC.

Conclusions: The results highlighted that altered integrity in the body of CC served as the shared basis of MDD and BD, and distinct microstructural WM abnormalities also existed, which might induce the various clinical manifestations of these two affective disorders. The study was registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number: CRD42022301929.