Brain Research最新文献

Phonological awareness reflects linguistic knowledge related to the sound system of a language. Individual development of phonological awareness is known to progress from larger to smaller sized units and is promoted by the acquisition of literacy, especially in alphabet-based writing systems that are built around sound-to-symbol correspondences. The present study addressed the nature of phonological awareness in speakers of a logographically scripted language. It investigated phonological awareness in adult speakers of Cantonese hailing from Hong Kong who (compared to speakers of other logographically scripted languages) traditionally received little sound-based assistance from tools like Pinyin or Zhu-yin-Fu-Hao when they acquired orthography. The study adopted an individual difference approach, quantifying individually variable levels of experience with a sound-to-symbol writing system and their relationship to phonological awareness. Fifty-seven Hong-Kong speakers of Cantonese took part online, completing rhyme judgment and phoneme monitoring tasks, alongside an extensive background questionnaire. The main prediction that Cantonese speakers who had a relatively high level of experience with sound-to-symbol writing would show an advantage in phonological awareness at the subsyllabic level was largely borne out by the data. The findings of the present study suggest that phonological awareness is a complex set of dissociable skills, shaped by the linguistic and orthographic experience of individual speakers.

Background

Postural control imposes higher demands on the central neural system (CNS), and age-related declines or incomplete CNS development often result in challenges performing tasks like forward postural leaning. Studies on older adults suggest increased variability in center of pressure (COP), greater muscle co-activations, and reduced corticospinal control during forward leaning tasks. However, the understanding of these features in children remains unclear. Specifically, it is uncertain whether forward leaning poses greater challenges for young children compared to adults, given the ongoing maturation of CNS during development. Understanding the distinct neuromuscular patterns observed during postural leaning could help optimize therapeutic strategies aimed at improving postural control in pediatric populations.

Methods

12 typically developing children (5.91 ± 1.37 years) and 12 healthy young adults (23.16 ± 1.52 years) participated in a dynamic leaning forward task aimed at matching a COP target in the anterior-posterior direction as steadily as possible. Participants traced a triangular trajectory involving forward leaning (FW phase) to 60 % of their maximum lean distance and backward returning (BW phase) to the neutral standing position. Surface electromyography (sEMG) from muscles including gastrocnemius medialis (GM), soleus (SOL), and tibialis anterior (TA) were collected during both phases. COP variability was assessed using the standard deviation (SD) of COP displacements. Muscle co-activation indexes (CI) for ankle plantar and dorsal flexors (SOL/TA, GM/TA) were derived from sEMG activities. Intermuscular coherence in the beta band (15–30 Hz) was also analyzed to evaluate corticospinal drive.

Results

Children exhibited a significantly greater SD of COP compared to young adults (p < 0.01) during the BW phase. They also demonstrated higher CI (p < 0.05) and reduced coherence of SOL/TA (p < 0.05) compared to young adults during this phase. No significant group differences were observed during the FW phase. Within the children’s group, COP variability was significantly higher in the BW phase compared to the FW phase (p < 0.01). Moreover, children displayed greater CI (p < 0.01) and reduced coherence of SOL/TA (p < 0.01) during the BW phase compared to the FW phase. Conversely, no significant phase effects were observed in the adult group. Furthermore, sEMG measures were significantly correlated with COP variability (p < 0.05).

Conclusions

The findings of this small study suggest that age-related differences in CNS development influence the modulation of corticospinal drive to ankle muscles (e.g., SOL/TA) during childhood, particularly supporting the existence of a separate pathway underlying the control of forward lean and backward returning.

Kainic acid (KA)-induced excitotoxicity induces acute degradation of phospholipids and release of free fatty acids (FFAs) in rodent hippocampus, but the long-term changes in phospholipids or the subcellular origins of liberated FFAs remain unclarified. Phospholipids and FFAs were determined in KA-damaged mouse hippocampus by enzyme-coupled biochemical assays. The evolution of membrane injuries in the hippocampus was examined by a series of morphological techniques. The levels of phospholipids in the hippocampus decreased shortly after KA injection but recovered close to the control levels at 24 h. The decline in phospholipids was accelerated again from 72 to 120 after KA treatment. The levels of FFAs were negatively related to those of phospholipids, exhibiting a similar but opposite trend of changes. KA treatment caused progressively severe damage to vulnerable neurons, which was accompanied by increased permeability in the cell membrane and increased staining of membrane-bound dyes in the cytoplasm. Double fluorescence staining showed that the latter was partially overlapped with abnormally increased endocytic and autophagic components in damaged neurons. Our results revealed intricate and biphasic changes in phospholipid and FFA levels in KA-damaged hippocampus. Disrupted endomembrane system may be one of the major origins for KA-induced FFA release.

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and synaptic dysfunction. Emerging evidence suggests a significant relationship between gut microbiota and brain health, mediated through the gut-brain axis. Alterations in gut microbiota composition may influence AD progression by affecting molecular pathways and miRNA interactions.

Methods

We retrieved and analyzed microarray data from 34 tissue samples of AD patients and controls (GEO accession number GSE110298). Differentially expressed genes (DEGs) with the GCS score package in R, considering a p-value < 0.05 and logFC<-1 and logFC>1 to isolate significant gene clusters. Enrichment analysis of signaling pathways and gene ontology was conducted using Enrichr, KEGG, Panther, DAVID, and shiny GO databases. Protein-protein interactions were visualized with Networkanalyst and CytoScape. Gut microbiota in 200 CE patients was analyzed using next-generation sequencing (NGS) data from gutMDisorder and GMrepo databases. miRNA interactions were evaluated using miEAA, Targetscan, MienTurnet, and miRnet databases.

Results

Significant reductions in microbial taxa, including Clostridia (LDA score −4.878208), Firmicutes (LDA score −4.817032), and Faecalibacterium (LDA score −4.40714), were observed in AD patients. Pathway analysis highlighted the involvement of Axon guidance, ErbB, and MAPK signaling pathways in AD. Venn diagram analysis identified 619 intersecting genes in brain and gut tissues, emphasizing pathways such as Axon Guidance and Cell Cycle. miRNA analysis revealed important regulatory miRNAs, including hsa-let-7c, hsa-mir-125b-2, and hsa-mir-145, which target key transcription factors involved in AD pathology.

Conclusion

The study demonstrates significant dysbiosis in the gut microbiota of AD patients and underscores the potential role of gut microbiota in AD progression through altered signaling pathways and miRNA interactions. These findings highlight the need for further research into microbiota-based interventions as potential therapeutic strategies for AD.

Peripheral viral infections are well known to profoundly alter brain function; however detailed mechanisms of this immune-to-brain communication have not been deciphered. This review focuses on studies of cerebral effects of peripheral viral challenge employing intraperitoneal injection of a viral mimetic, polyinosinic-polycytidylic acid (PIC). In this paradigm, PIC challenge induces the acute phase response (APR) characterized by a transient surge of circulating inflammatory factors, primarily IFNβ, IL-6 and CXCL10. The blood-borne factors, in turn, elicit the generation of CXCL10 by hippocampal neurons. Neurons also express the cognate receptor of CXCL10, i.e., CXCR3 implicating the existence of autocrine/paracrine signaling. The CXCL10/CXCR3 axis mediates the ensuing neuroplastic changes manifested as neuronal hyperexcitability, seizure hypersusceptibility, and sickness behavior. Electrophysiological studies revealed that the neuroplastic changes entail the potentiation of excitatory synapses likely at both pre- and postsynaptic loci. Excitatory synaptic transmission is further augmented by PIC challenge-induced elevation of extracellular glutamate that is mediated by astrocytes. In addition, the hyperexcitability of neuronal circuits might involve the repression of inhibitory signaling. Accordingly, CXCL10 released by neurons activates microglia whose processes invade perisomatic inhibitory synapses, resulting in a partial detachment of the presynaptic terminals, and thus, de-inhibition. This process might be facilitated by the cerebral complement system, which is also upregulated and activated by PIC challenge. Moreover, CXCL10 stimulates the expression of neuronal c-fos protein, another index of hyperexcitability. The reviewed studies form a foundation for full elucidation of the fascinating intersection between peripheral viral infections and neuroplasticity. Because the activation of such pathways may constitute a serious comorbidity factor for neuropathological conditions, this research would advance the development of preventive strategies.

Background

Alzheimer’s disease (AD) remains a significant global health challenge, with its etiology intricately linked to a variety of genetic and environmental factors. Among these, lipid metabolism has been hypothesized to play a crucial role, though the causal pathways remain inadequately elucidated. This study aims to employ Mendelian Randomization (MR) to unravel the potential causal relationships between a comprehensive array of lipid species and the risk of developing AD.

Methods

Utilizing a two-sample MR framework, we analyzed data from genome-wide association studies (GWAS) encompassing 487,511 individuals of European descent. A total of 179 lipid species across 13 lipid categories were investigated for their causal association with AD. Genetic variants serving as instrumental variables (IVs) were carefully selected based on stringent criteria to ensure validity. The statistical analyses, including inverse variance weighting (IVW), weighted median-based estimation, and sensitivity analyses, were conducted using the R software environment.

Results

Our findings reveal a significant causal relationship between ten specific lipid species and the risk of AD. Notably, certain lipids such as Sterol ester (27:1/15:0) and Phosphatidylcholine (16:0_22:4) exhibited a protective effect against AD, as evidenced by their inverse correlation with the disease’s risk. Additionally, a reciprocal analysis suggested a negative causal impact of AD on the levels of certain Triacylglycerol species. The integrity of our results was reinforced by sensitivity analyses, including the MR Egger intercept test, indicating the absence of horizontal pleiotropy and confirming the reliability of our findings.

Conclusions

This study substantiates the causal link between specific lipid species and Alzheimer’s disease, highlighting the complex interplay between lipid metabolism and AD pathogenesis. The identified lipid biomarkers offer new insights into the disease’s etiology and potential therapeutic targets. Furthermore, our rigorous methodological approach demonstrates the utility of MR in disentangling the causal relationships in complex diseases.

Schizophrenia is believed to be, at least in part, a dysfunction of the glutamatergic system. In line with anatomical evidence, suppressing N-methyl-D-aspartate (NMDA) neurotransmission leads to symptoms that are characteristic of schizophrenia. Rodent models of schizophrenia often involve the acute application of NMDA antagonists, which produce both behavioural and brain activity changes that closely resemble symptoms observed in schizophrenia. It is, however, important to note that the full spectrum of schizophrenia symptoms may not be manifested following the acute suppression of NMDA receptors. This has led to the proposal of a chronic model where NMDA receptors are suppressed for prolonged periods. Although the chronic model has shown promising results from a behavioural perspective and alterations in metabolic processes in the brain, its impact on brain oscillations remains largely unknown. The aim of this study is to examine the impact of acute and chronic NMDA neurotransmission suppression on brains’ oscillatory activity. To achieve this, chronic brain activity recordings in mice of both sexes were used to assess both spontaneous and evoked brain oscillations. The study demonstrates that an acute suppression of NMDA receptors alters brain oscillations across a wide frequency spectrum and diminishes the oscillatory potency in evoked responses, paralleling changes observed in schizophrenia. However, the chronic suppression of NMDA receptors did not have the expected cumulative effect on brain activity. This research highlights the robust yet similar impacts of acute and chronic NMDA receptor suppression on brain activity, contributing to the nuanced understanding of rodent models of schizophrenia.

Excessive iron accumulation in the brain plays a significant role in neurodegenerative processes, contributing to the pathogenesis of Alzheimer’s disease (AD). AD, a prominent neurological disorder affecting the central nervous system, is characterized by the accumulation of beta-amyloid (Aβ) and tau phosphorylation. This accumulation leads to the subsequent development of cognitive impairments, particularly in learning and memory functions. This study investigates the neuroprotective effects of emoxypine succinate in a zebrafish model of iron overload-induced neurodegeneration. Iron was administered to the zebrafish for 28 days to induce neurodegeneration. Following induction, Emoxypine succinate was employed as a treatment intervention for 14 days (concentrations of 4 mg/L, 8 mg/L, and 12 mg/L). Following the end of the treatment, behavioral tests (Y maze test, Novel tank test) were conducted on the zebrafish, and the biochemical (MDA, Catalase, SOD, GSH) and molecular parameters (AchE, Iron levels, IL-1β, TNF-α, CDK-5, GSK-3β, and NLRP3) of the zebrafish brain were also assessed. In the novel tank test, emoxypine succinate-treated groups exhibited significantly increased time in the upper zone (p < 0.001), higher distance travelled (p < 0.001), and shorter latency to the top (p < 0.001) compared to the negative control. Similarly, the Y-maze test revealed improved time in the novel arm (p < 0.001) and total distance travelled (p < 0.001) in treated groups versus the negative control. Assessment of oxidative stress parameters demonstrated significant reductions in oxidative stress in emoxypine succinate-treated groups. Furthermore, AChE activity decreased significantly (p < 0.001), and brain iron levels decreased substantially (p < 0.001) in treated groups, indicating positive therapeutic outcomes. Molecular analysis showed a significant reduction in pro-inflammatory markers like IL-1β, TNF-α, CDK-5, GSK-3β, and NLRP3 (p < 0.001). This comprehensive study highlights the potential efficacy of emoxypine succinate in mitigating neurodegeneration associated with iron dysregulation.