Journal of integrative neuroscience最新文献

Background: Evidence suggests that subjective cognitive decline (SCD) involves abnormal structures and functional alterations in multiple brain networks, rather than a single brain region. Acupuncture has shown a positive therapeutic effect in treating SCD, although whether and how it can improve cognitive decline by altering large-scale brain network organization is unclear.

Methods: We utilized resting-state functional magnetic resonance imaging (fMRI) data from 66 individuals with SCD (derived from a previous randomized controlled trial) and explored brain-wide network-level functional connectivity and topological property changes after 12 weeks of acupuncture intervention to examine its therapeutic mechanisms. The Auditory Verbal Learning Test-Huashan version (AVLT-H) test was used to measure objective memory performance. Neuroimaging outcomes included brain network functional connectivity and topological properties obtained from resting-state fMRI. A repeated-measures general linear model and mixed-effect analysis were used to examine group × time interaction effects on cognitive function and neuroimaging outcomes. Correlation analyses were used to examine the relationship between functional connections (FCs) and memory performance.

Results: Compared with sham acupuncture, 12 weeks of acupuncture treatment significantly improved the objective memory performance of individuals with SCD. Five FCs within the sensorimotor network (SMN) and between the SMN and the cingulo-opercular network (CON) showed significant alterations after acupuncture. Two intrinsic SMN connections were enhanced by acupuncture, whereas inter-network FCs changed oppositely, negatively correlating with memory improvement. The topological properties of two regions within the SMN were also significantly modulated after acupuncture.

Conclusions: The results suggest that 12 weeks of acupuncture may improve objective memory performance in SCD, potentially by reducing FCs between the SMN and CON. Enhancing functional segregation of these networks may be a potential target for acupuncture treatment.

Clinical trial registration: No: NCT03444896. https://www.

Clinicaltrials: gov/study/NCT03444896.

Background: Lysine-Specific Demethylase 1A (Kdm1a) is the first discovered histone lysine-specific demethylase, and mutations in kdm1a have been detected in neurodevelopmental disorders. However, the effect of kdm1a on neurobehaviors and the underlying mechanisms remain largely unknown.

Methods: In this study, kdm1a deficient zebrafish were constructed using (clustered regularly interspaced short palindromic repeat) Clustered Regularly Interspaced Short Palindromic Repeats/CRISPRassociated protein 9 (CRISPR/Cas9) and the neurodevelopment was systematically assessed by a series of behavioral tests.

Results: We found that kdm1a knockout zebrafish exhibited developmental toxicity and abnormal neurobehaviors, including locomotor abnormalities, and learning and memory deficits. Kdm1a deficiency suppressed central nervous system (CNS) neurogenesis in Tg (HuC:egfp) zebrafish, reduced motor neuron axon length in Tg (hb9:egfp) zebrafish and downregulated the expression of neurodevelopment related genes at 96 hours post fertilization (hpf). In addition, the expression of genes related to autophagy and apoptosis increased significantly in kdm1a knockout zebrafish.

Conclusions: These results indicated that kdm1a deficiency induced locomotor abnormalities and learning and memory deficits in zebrafish larvae accompanied by activation of autophagy and apoptosis. These findings indicate a key role of kdm1a in neurodevelopment, providing novel insights into the mechanisms underlying the neurodevelopmental disorders.

Metaphors are a core category of cognitive linguistics and an important mode of human thinking. They concretize abstract concepts through cross-domain mapping and build a bridge between cognition and understanding in verbal communication and interpersonal communication. Metaphor research has shifted from a pure linguistic perspective to multidisciplinary and multimodal research. However, there has yet been no systematic review of how the brain processes the differentiation and integration mechanism of verbal and non-verbal modal metaphorical information, as well as the main influencing factors. In particular, a weak area in current research is how special groups achieve compensation of metaphorical understanding through neuroplasticity. This review systematically describes the relevant achievements in cognitive neuroscience in recent years, with the aim of revealing the main influencing factors of multimodal metaphor processing and the process of neural differentiation and cross-modal integration. This review also focuses on the compensatory mechanisms in autism, aphasia, and deafness, and describes how they achieve effective metaphorical understanding through the reconstruction of neuroplasticity. Moreover, it provides an integrated perspective for understanding the neural basis of metaphorical cognition, as well as a theoretical basis and practical guidance for advancing multimodal metaphor research and applications in rehabilitation. Future research should combine temporal neurodynamic technology with ecological interventions designed to further promote advancement in this field.

Background and purpose: Current intrathecal (IT) catheter techniques in rats are problematic due to complex surgical procedures and frequent blockages. This study developed a simpler, faster, and more reliable method for long-term IT catheter placement.

Methods: Fifty adult male Sprague-Dawley rats were randomly divided into three groups: IT group (n = 30), Sham group (n = 10), and Control group (n = 10). We inserted a polytetrafluoroethylene (PTFE) catheter (0.5-mm outer diameter, 0.3-mm inner diameter) into the cauda equina, reaching a depth of 0.5-1 cm via the L5-L6 intervertebral space. Then catheter was tunneled subcutaneously, exiting at the dorsal neck, and held in place with mechanical compression. We assessed safety and efficacy over 12 weeks through behavioral testing, functional evaluations, and immunofluorescence analysis.

Results: Surgery took an average of 7.2 ± 1.8 min, with a 93.3% first-attempt success rate. Remarkably, all catheters remained patent throughout the 12-week study period (100% patency). Behavioral tests showed no changes in pain sensitivity, although rats did experience a temporary reduction in weight gain during the first postoperative week (p < 0.01). Lidocaine testing confirmed proper catheter function, with motor block occurring rapidly (onset: 30 ± 5 s), followed by complete recovery. Lipopolysaccharide doses of 3, 15, and 30 μg demonstrated clear dose-dependent inflammatory responses, confirming accurate drug delivery. Western blot analysis confirmed no chronic inflammation, with interleukin 1 beta (IL-1β), IL-6, and tumor necrosis factor alpha expression in the IT-Saline group comparable with controls (p > 0.05). Immunofluorescence analysis revealed no significant activation of microglia (ionized calcium-binding adaptor molecule 1) or astrocytes (glial fibrillary acidic protein) based on mean fluorescence intensity, with preserved neuronal density (NeuN-positive cells) comparable with controls.

Conclusion: Our L5-L6 approach effectively minimized the risk of spinal cord injury. The choice of PTFE material proved crucial, as it enabled 100% long-term patency, a result not achieved with other materials. Combined with the neck-mounted external design, this technique offers an improved approach for repeated IT drug delivery in rat models, but more studies are needed to confirm its effectiveness in a wider range of pharmacological applications.

Background: Thalamic hemorrhage (TH) is a severe neurological condition, the molecular mechanisms of which are poorly understood, particularly in clinical settings. N-acetyltransferase 10 (NAT10), a regulator of RNA N4-acetylcytidine (ac4C) modification, has been implicated in cell cycle regulation and identified as a potential therapeutic target. This study explored the effects of NAT10 inhibition on TH pathology using a multi-omics approach.

Methods: A mouse model of TH was established via collagenase IV injection. NAT10 activity was detected by dot blot and inhibited using Remodelin. Comprehensive multi-omics analyses, including 16S ribosomal Deoxyribonucleic Acid (16S rDNA) sequencing, metabolomics, and transcriptomics, were used. Behavioral, histological, and molecular evaluations were conducted to evaluate the key genes.

Results: A total of 35 hub genes, 30 hub metabolites, and 28 hub microorganisms associated with NAT10 inhibition were identified. Among them, the xanthine dehydrogenase (XDH) and guanine deaminase (GDA) genes were linked to xanthine, which is a key metabolite implicated in TH pathology. Based on these findings, the xanthine oxidase inhibitor febuxostat was tested, demonstrating significant therapeutic benefits in TH-affected mice. Behavioral, histological, and molecular evaluations confirmed that NAT10 inhibition alleviated TH-induced damage.

Conclusions: This study provides the first comprehensive molecular insights into the therapeutic potential of NAT10 inhibition in TH. Moreover, it identified NAT10 inhibitors and febuxostat as promising candidates for TH management, paving the way for future therapeutic development targeting NAT10 in this condition.

Cardiovascular modulation in response to movement and gravitational forces can be influenced by vestibular input or peripheral baroreflex mechanisms. Galvanic vestibular stimulation (GVS) is a widely used, noninvasive method for activating neural pathways within the vestibular system, as well as associated pathways such as vestibulo-spinal, oculomotor, and vestibulo-autonomic circuits. Research on vestibulo-autonomic function via GVS has primarily focused on its effects on cardiovascular modulation and sympathetic muscle and nerve activity. However, inconsistencies in GVS application protocols across studies have made it challenging to reach a consensus regarding its effectiveness in modulating the vestibulo-autonomic pathway. Evidence suggests that GVS induces transient autonomic changes by stimulating a neural pathway sensitive to otolith input. This review collates the parameters used in GVS application and examines their effects on autonomic neural pathways by analyzing variations in amplitude, frequency, and electrode montage to understand their impact on autonomic responses, including changes in heart rate (HR), blood pressure (BP), and sympathetic muscle or nerve activity (MSNA). By analyzing stimulation parameters and experimental protocols, we aim to determine their impact on autonomic activation and evaluate their potential for precise autonomic modulation. Finally, based on the evidence generated in populations with neurological disorders and motion sickness, we discuss the potential of GVS as a complementary neuromodulation strategy to treat autonomic dysregulation.

Background: Obstructive sleep apnea (OSA) is associated with widespread higher-order cognitive consequences, including deficits in memory and executive function. However, the specific cognitive architecture and underlying mechanisms that link the disease's pathophysiology to these broad cognitive changes remain poorly understood. This study tested the hypothesis that a selective vulnerability of the working memory (WM) executive control system serves as a central hub, mechanistically mediating the relationship between OSA disease burden and memory retention.

Methods: Thirty male patients with OSA underwent comprehensive polysomnography and neurocognitive assessment. A data-driven Global Severity Index (GSI) was derived from principal component analysis of the most cognitively-relevant physiological metrics. A multi-task paradigm was used to dissociate performance on tasks of WM maintenance capacity from those requiring executive control. Hierarchical linear regression and mediation analyses were performed, controlling for relevant covariates.

Results: A higher GSI was consistently associated with poorer performance across multiple tasks requiring executive control, but not with measures of WM maintenance capacity or attentional control. Critically, the a priori defined mediation model was supported: the relationship between the GSI and memory retention performance was fully mediated by a latent Executive Control Factor (ECF) derived from the executive tasks.

Conclusions: Our findings delineate a specific mechanistic pathway for the cognitive consequences of OSA. The disease's pathophysiological burden is selectively associated with executive control performance, and this vulnerability appears to serve as a core mechanism that accounts for the disorder's downstream impact on memory function. This work identifies executive control as a critical target for mitigating the broader cognitive impact of OSA.

Background: Depression frequently manifests as a secondary affective disorder in individuals who have experienced a stroke. In laboratory rats subjected to stroke, prolonged exposure to chronic stress effectively replicates the physiological impairment and adverse environmental challenges encountered by stroke patients. Nevertheless, the complex mechanisms underlying these phenomena remain unclear.

Methods: To elucidate the mechanisms underlying these impairments, we established a poststroke depression model by combining middle cerebral artery occlusion (MCAO) with 70 minutes of ischemia and chronic unpredictable mild stress (CUMS) exposure. Behavioral assessments, along with analyses of purinergic ligand-gated ion channel 7 receptor (P2X7R) and nucleotide-binding oligomerization domain, leucine-rich repeats, and pyrin domain-containing protein 3 (NLRP3)-associated inflammatory protein levels and peripheral blood inflammatory cytokine levels, were conducted at 1, 2 and 4 weeks post-MCAO, and the results were compared with those of rats subjected to stroke alone.

Results: Depression-like behaviors were induced by CUMS exposure for three weeks. These changes were accompanied by significant increases in the protein levels of interleukin-1β (IL-1β), caspase-1, NLRP3 and Iba-1 in the hippocampus. Additionally, an increase in the fluorescence intensity of Iba-1, P2X7R, and NLRP3 in the Cornu Ammonis 1 (CA1) region was observed, along with dysregulation of plasma IL-6, IL-4, IL-10, and IL-1β levels. Importantly, the interaction of CUMS exposure and time affected behavioral scores and the levels of IL-1β. Notably, intraperitoneal administration of Brilliant blue G reversed depression-like behaviors and reduced the expression of NLRP3, caspase-1, IL-1β and IL-18 in the affected hippocampus.

Conclusions: These findings are consistent with the involvement of P2X7R/NLRP3 signaling in hippocampal impairment and inflammation/immune dysregulation in the context of depression-like behaviors induced by CUMS. In particular, behavioral scores may be affected by the interaction between CUMS exposure and time.

Background: Adding movement sonification to haptic exploration can change the perceptual outcome of a textured surface through multisensory processing. We hypothesized that auditory-evoked emotions influence the appraisal of textured surfaces, with corresponding changes reflected in cortical excitability.

Methods: Twelve participants actively rubbed two different textured surfaces (slippery and rough) either without movement sonification, or with pleasant or disagreeable movement sonification.

Results and discussion: We found that sounds, whether agreeable or disagreeable, did not change the texture appraisal. However, the less pleasant surface was associated with a stronger negative hedonic valence, particularly when paired with disagreeable movement sonification. Time frequency analyses of electroencephalography (EEG) activities revealed a significant reduction in beta-band power [15-25 Hz] within the source-estimated sensorimotor and superior posterior parietal cortices when contrasting both pleasant and unpleasant sounds with the silent touch. This suggests that the primary somatosensory cortices together with the superior parietal regions participated in the audio-tactile binding, with both pleasant and unpleasant sounds. In addition, we observed a significant increase in beta-band power in medial visual areas, specifically when disagreeable movement sonification was paired with tactile exploration. This may reflect a disengagement of visual cortical processing, potentially amplifying auditory-driven emotional responses and intensifying the perceived unpleasantness of the explored surfaces.

Conclusion: Our results offer new insights into the neural mechanisms by which hedonic valence of auditory signals modulates emotional processing, without disrupting the perceptual analysis of texture properties.

Background: Alzheimer's disease (AD) is a severe neurodegenerative disorder that impacts the global impact on the population. Nevertheless, the intricate nature of its pathogenesis has posed significant challenges to drug discovery in this field. This study aimed to verify the therapeutic potential of rubiadin (RB) on AD through both in vivo and in vitro experiments, thereby facilitating translational research for the advancement of AD treatment.

Methods: We investigated the neuroprotective effects of RB on AD using both in vivo and in vitro models. Immunohistochemistry and western blot analysis were employed to evaluate inflammatory factors and the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in Mo/HuAPP695swe (APP)/PS1-dE9 (PS1) mice and N2a cells.

Results: RB enhanced the memory performance of APP/PS1 mice in various tests, including the Morris water maze, step-down and step-through passive avoidance tasks, and novel object recognition. RB reduced the accumulation of Amyloid-beta (Aβ) plaques, as shown by immunohistochemical analysis. It also decreased the expression levels of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α), while increasing the release of IL-4. Additionally, RB inhibited the NF-κB pathway, as demonstrated by western blot. Moreover, a cell viability test showed that RB protected N2a cells against toxicity caused by Aβ_1-42 through a cell viability test. Western blot analysis revealed that neuroinflammation and the NF-κB pathway were inhibited by RB treatment in Aβ_1-42-induced N2a cells. Accordingly, RB suppressed the nuclear translocation of NF-κB in Aβ_1-42-induced N2a cells.

Conclusions: Our results provide experimental evidence supporting the preclinical research and future clinical applications of RB, thereby facilitating the development of new drugs for AD clinical therapy.