Brain Research最新文献

Cerebrovascular diseases (CVDs) include conditions such as stroke, cerebral amyloid angiopathy (CAA) and cerebral small vessel disease (CSVD), which contribute significantly to global morbidity and healthcare burden. The pathophysiology of CVD is complex, involving inflammatory, cellular and vascular mechanisms. Recently, research has focused on triggering receptor expressed on myeloid cells 2 (TREM2), an immune receptor predominantly found on microglia. TREM2 interacts with multiple signalling pathways, particularly toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB), inhibiting patients’ inflammatory response. This receptor plays an essential role in both immune regulation and neuroprotection. TREM2 deficiency or dysfunction is associated with impaired microglial responses, exacerbated neurodegeneration and neuroinflammation. Up until recently, TREM2 related studies have focused on neurodegenerative diseases (NDs), however a shift in focus towards CVDs is beginning to take place. Advancements in CVD research have focused on developing therapeutic strategies targeting TREM2 to enhance recovery and reduce long-term deficits. These include the exploration of TREM2 agonists and combination therapies with other anti-inflammatory agents, which may synergistically reduce neuroinflammation and promote neuroprotection. The modulation of TREM2 activity holds potential for innovative treatment approaches aimed at improving patient outcomes following cerebrovascular insults. This review compiles current research on TREM2, emphasising its molecular mechanisms, therapeutic potential, and advancements in CNS disease research.

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.

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.

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.

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.