Journal of integrative neuroscience最新文献

The onset and progression of central nervous system (CNS) disorders are frequently associated with aberrant neuronal death. In addition to the classical forms of cell death such as apoptosis and necrosis, neurons can also undergo alternative modes of death, including ferroptosis, cuproptosis, and ammonia-induced cell death, all of which may involve the participation of astrocytes. Neuronal death is an irreversible process and plays a central role in the pathogenesis of numerous CNS diseases. We found that astrocytes exhibit the capacity to regenerate into neurons, a characteristic that may pave the way for novel therapeutic approaches in the treatment of neurological disorders. Astrocytes represent optimal starting cells for reprogramming techniques due to their anatomical proximity to neurons and their shared origin from common progenitor cells-radial glial cells. Reprogramming techniques encompass the conversion of astrocytes into pluripotent neurospheres or their direct in vivo reprogramming into functional neurons, aiming to replace damaged or lost neurons through processes such as transdifferentiation and dedifferentiation. This article examines the interplay between astrocytes and neuronal survival and degeneration in CNS disorders, as well as two reprogramming strategies for converting astrocytes into neurons, with the aim of establishing a scientific foundation for neuronal repair in the treatment of CNS diseases.

Background: To address the unmet need for targeted therapeutic strategies for neonatal hypoxic-ischemic encephalopathy (HIE), we developed a brain-targeting lipid nanoparticle delivery system capable of silencing circular RNA homeodomain-interacting protein kinase 2 (circHIPK2) in astrocytes and investigated its ability to mediate neuroinflammation and improve neurological outcomes.

Methods: Dual-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly (ethylene glycol)-neurotropic virus-derived peptide (DSPE-PEG2000-RVG29) peptide/mannose-functionalized lipid nanoparticles loaded with circHIPK2 small interfering RNA (M-R@siC-NPs) were constructed, and their physicochemical properties, stability, and biocompatibility were characterized. Using an in vitro oxygen-glucose deprivation (OGD) model and a neonatal murine hypoxic-ischemic brain damage (HIBD) model, we evaluated the effects of circHIPK2 silencing by the M-R@siC-NPs on the expression of two astrocyte activation markers, glial fibrillary acidic protein (GFAP) and interleukin-1β (IL-1β), via western blotting, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and immunofluorescence staining. Neurobehavioral recovery was assessed through righting reflex, negative geotaxis, and Morris water maze tests.

Results: M-R@siC-NPs exhibited a uniform size distribution (134 nm), good blood-brain barrier penetrability, and astrocyte-targeting specificity. The nanoparticles effectively silenced circHIPK2 while demonstrating excellent colloidal stability and biosafety. In vitro, circHIPK2 knockdown by M-R@siC-NPs markedly suppressed OGD-induced astrocyte activation, reducing GFAP and IL-1β expression (p < 0.01). In HIBD mice, M-R@siC-NPs attenuated hippocampal astrocyte activation and improved motor coordination (shortened righting reflex latency, p < 0.0001) and spatial memory (increased platform crossings in Morris water maze, p < 0.0001).

Conclusions: The RVG29/mannose dual-modified M-R@siC-NPs precisely regulated astrocyte activation and attenuated neuroinflammation, effectively ameliorating brain injury in HIBD mice. This study establishes a novel RNA interference-based therapeutic strategy for targeted neuroinflammatory modulation, providing a promising translational platform for HIE treatment.

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.

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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.