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.
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.
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.
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.
The early years of life show remarkable brain development and cognitive growth. During this time, the foundations for learning and memory are established, driven by the intricate interplay of various brain structures. Understanding the neuroanatomy of infant learning and retention is crucial in elucidating how these processes evolve and contribute to lifelong cognitive capabilities. Herein, we review the complex processes of brain development, learning and memory in the fetus, and during the first two years of life postpartum. Neural connections and key brain structures start to form during the fetal stage and continue after birth. We discuss how fetuses, infants, and toddlers absorb stimuli from their environment and develop learning and memory capabilities. We also provide an updated review of recent research findings in the field, presenting the latest insights into the development of learning and memory in the fetus and infants. In addition, we compare changes in learning and memory with electroencephalography findings from early childhood.
This study addressed three key challenges in subject-independent electroencephalography (EEG) emotion recognition: limited data availability, restricted cross-domain knowledge transfer, and suboptimal feature extraction. The aim is to develop an innovative framework that enhances recognition performance while preserving data privacy.
This study introduces a novel multi-teacher knowledge distillation framework that incorporates data privacy considerations. The framework first comprises n subnets, each sequentially trained on distinct EEG datasets without data sharing. The subnets, excluding the initial one, acquire knowledge through the weights and features of all preceding subnets, enabling access to more EEG signals during the training process while maintaining privacy. To enhance cross-domain knowledge transfer, a multi-teacher knowledge distillation strategy was designed, featuring knowledge filters and adaptive multi-teacher knowledge distillation losses. The knowledge filter integrates cross-domain information using a multi-head attention module with a gate mechanism, ensuring effective inheritance of knowledge from all previous subnets. Simultaneously, the adaptive multi-teacher knowledge distillation loss dynamically adjusts the direction of knowledge transfer based on filtered feature similarity, preventing knowledge loss in single-teacher models. Furthermore, a spatio-temporal gate module is proposed to eliminate unnecessary frame-level information from different channels and extract important channels for improved feature representation without requiring expert knowledge.
Experimental results demonstrate the superiority of the proposed method over the current state of the art, achieving a 2% performance improvement on the DEAP dataset.
The proposed multi-teacher distillation framework with data privacy addresses the challenges of insufficient data availability, limited cross-domain knowledge transfer, and suboptimal feature extraction in subject-independent EEG emotion recognition, demonstrating strong potential for scalable and privacy-preserving emotion recognition applications.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
No: NCT03444896. https://www.clinicaltrials.gov/study/NCT03444896.
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.
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.
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.
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.
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.
In Parkinson’s disease (PD), levodopa-induced dyskinesia (LID) represents a common motor complication of long-term dopaminergic therapy. Although levodopa remains the most effective treatment for PD, the neurological mechanisms underlying the LID remain incompletely understood. This study aimed to investigate the pattern of cortical morphological and subcortical structural alterations associated with LID in PD.
Clinical data and T1-weighted structural brain images were obtained for 62 patients with PD, including 30 with LID and 32 without LID, along with 30 healthy controls (HCs). Regional sulcal depth (SD) and subcortical volumes were quantified to assess alterations in cortical surface morphology and subcortical structures. The study further aimed to evaluate the association between structural indicators and the severity of LID, as well as to determine their potential diagnostic ability.
PD patients with LID demonstrated reduced regional SD in the right inferior parietal and insula cortices, compared with PD patients without LID and HCs (after Bonferroni correction). The right putamen volume in both PD subtypes was lower than that of HCs (after Bonferroni correction). In particular, the level of right inferior parietal SD was negatively associated with the severity of LID (r = –0.494, p = 0.017). Receiver operating characteristic (ROC) curve analyses further revealed that the combination of cortical SD values demonstrated excellent performance in distinguishing PD-LID from PD-non-levodopa-induced dyskinesia (NLID) (area under the curve [AUC] = 0.913).
Our main findings show that structural alterations associated with LID extend from the frontal to the parietal and insula cortices, suggesting that decreased cortical SD values in these regions may contribute to a better understanding of the neurological underpinnings of LID in PD.
Parkinson’s disease (PD) is characterized by progressive dopaminergic neurodegeneration. Melatonin (MLT) is implicated in neuroprotection, yet the effects of modulating its receptors remain unclear. This study investigated the impact of the MLT receptor agonist agomelatine (AG) and antagonist luzindole (LU) on motor behavior, serum MLT levels, and dopaminergic neuron survival in a 6-hydroxydopamine (6-OHDA) rat model of PD.
A PD model was induced by stereotaxic injection of 6-OHDA into the medial forebrain bundle. Rats received intraperitoneal AG or LU for 2 or 4 weeks. Motor function was assessed using the apomorphine-induced rotation test. Tyrosine hydroxylase (TH) and MLT receptor (MEL-1A/B) expression in the substantia nigra and striatum were evaluated by immunohistochemistry and Western blot. Serum MLT concentrations were measured using ELISA. Pearson’s correlation analysis was performed to examine associations among serum MLT levels, TH expression, and motor performance.
AG significantly improved motor function, increased serum MLT levels, and enhanced TH expression in PD rats. LU also mitigated motor deficits and preserved dopaminergic neurons, despite reducing serum MLT levels. Correlation analysis revealed a dynamic temporal relationship between MLT levels, behavioral outcomes, and dopaminergic neuron survival, indicating that MLT signaling may differentially influence PD pathology at various stages.
Both AG and LU demonstrated neuroprotective potential in 6-OHDA–induced PD rats. AG may exert its effects by enhancing endogenous MLT signaling, while LU may protect neurons by modulating excessive MLT activity. These findings highlight the complex regulatory role of the MLT pathway in PD progression and suggest stage-dependent therapeutic benefits of MLT receptor modulators.
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.
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.
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.
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.