Neuroscience最新文献

Alzheimer's disease (AD) is a common neurodegenerative disease, neuroinflammation is an early pathological feature of AD. However, the alteration of the immune microenvironment in asymptomatic AD was not fully explained. In this study, we aimed to utilize the transcriptome data of AD patients in public databases to reveal the change of immune microenvironment in asymptomatic AD and screen the potential anti-AD drug. Through a series of bioinformatics analyses, differentially expressed genes (DEGs) screening, enrichment analysis, PPI network construction, and hub gene identification were done. Meanwhile, the hub genes were validated in APP/PS-1(AD) mice. Importantly, seven enrichment pathways and eight hub genes associated with inflammation were identified in asymptomatic AD. Early AD patients presented infiltration of immunoinflammatory cells to varying degrees in the four representative brain regions. Correspondingly, more hub genes changed in the hippocampus in AD mice compared to the other four brain regions. Accompanied by the activation of microglia and astrocytes, the inflammation cytokines were increased in the hippocampus of AD mice. Moreover, HLA-C was correlated with the activation of microglia, HLA-DRB1 with IL-6 and OAS2 with TGF-β1 in the hippocampus. Five FDA-approved drugs (Itrazole, Dfo, Syrosingopine, Cefoperazone and Pradaxa) were predicted as the common drug-targeted HLA-C and HLA-DRB1 by molecular docking. Taken together, the changes in the immune microenvironment of asymptomatic AD, and provided a new perspective for the development of anti-inflammatory drugs for AD early treatment.

The presence of ionotropic receptors to neurotransmitters in presynaptic structures is well documented in many synapses of the mammalian brain. However, due to technical limitations, the actual prevalence of presynaptic ionotropic receptors, as well as their potential functional roles, have remained largely uncertain. The relatively simple and regular organization of neurites in the cerebellar cortex has offered a unique opportunity to bridge this gap of knowledge, by systematically probing the presence and role of presynaptic ionotropic receptors at various synapses. In the present review, we describe the collective results for glutamate and GABA presynaptic receptors in this brain region. They indicate a surprisingly large prevalence of presynaptic ionotropic receptors, with many synapses displaying several such receptors, often to both neurotransmitters. These results indicate that the presence of several types of presynaptic ionotropic receptors may be the rule rather than the exception in mammalian brain synapses. In addition, we discuss the functional roles of presynaptic ionotropic receptors in the induction of various forms of cerebellar long-term synaptic plasticity, as well as the potential consequences of having multiple presynaptic ionotropic receptors in a single synapse.

Myelination is the process by which oligodendrocytes ensheath axons to form myelin sheaths. Myelination is a crucial aspect of brain development and is closely associated with central nervous system abnormalities. However, previous studies have found that advanced maternal age might affect the myelination of offspring, potentially through the pathway of disrupting DNA methylation levels in the offspring's hippocampus. Current research has demonstrated that ascorbic acid can promote hydroxymethylation to reduce methylation levels in vivo. This study aims to verify the relationship between ascorbic acid and myelination, as well as the specific mechanism involved. Initially, oligodendrocyte differentiation was observed using immunofluorescence and Western blot. Myelination was assessed through Luxol Fast Blue staining, Glycine silver staining, immunofluorescence, and transmission electron microscopy. The demethylation level of oligodendrocyte progenitor cells was detected by immunofluorescence co-expression of OLIG2 and DNA hydroxylase ten-eleven translocation 1 (TET1), TET2, and TET3. Our study found that advanced maternal age could impair myelination in the hippocampus and corpus callosum of offspring. Ascorbic acid intervention may induce TET1 and TET2-mediated hydroxymethylation to ameliorate myelination disorders, promote myelination and maturation, and reverse the effects of advanced maternal age on offspring.

Empathy deficiencies are prevalent among deaf individuals. It has yet to be determined whether they exhibit deficiencies in both trait empathy and state empathy, along with the effect of top-down attention. Here, the current study employed the IRI-C scale and physiological pain empathy tasks (A-P task and A-N task) to explore the temporal dynamics of neural activities when deaf individuals were processing second-hand painful/non-painful stimuli. For trait empathy, we found that deaf individuals have deficiencies in both emotional and cognitive empathy compared to their hearing counterparts. For state empathy, we found that deaf individuals showed stronger automatic emotional empathy responses and paid more cognitive evaluation resources. Moreover, the differential processing of empathy between deaf individuals and hearing individuals towards others' pain could be regulated by top-down attention, which occurs both in the early and late processing stages of pain empathy.

Patients experiencing severe hemiplegia following a stroke struggle to rehabilitate their affected limbs. Cross-education (CE) training emerges as a promising rehabilitation method due to its safety, simplicity, low risk, and ability to effectively improve muscle strength in the affected limb. However, controversy surrounds the neural mechanisms and clinical applications of CE. To address this, we employed functional near-infrared spectroscopy to monitor the response of regions of interest (ROI) and functional connectivity in patients with stroke experiencing severe hemiplegia during one session of 50% maximal voluntary contraction (MVC) strength training with less-affected hand in both subacute and convalescent phases. Our objective was to compare the two stroke groups to gain insight into the potential utility for unilateral training of the less-affected limb as an effective rehabilitation approach during different phases post of stroke. The findings revealed varying degrees of activation in the ROIs within the affected hemisphere across both groups during the task. Additionally, we found that the subacute stroke patients with severe hemiplegia (SPS) had higher blood oxygen levels in the ipsilesional primary motor (iM1), ipsilesional pre-motor and supplementary motor area (iP-SMA) and contralesional P-SMA (cP-SMA). Functional connectivity strength between the iM1 and contralesional brain regions, as well as between the iP-SMA and ipsilesional ROIs, showed statistically significant differences in SPS compared to convalescent stroke patients with severe hemiplegia (CPS) during a 50% MVC strength training session using the less-affected hand. SIGNIFICANCE STATEMENT: Exploring the neural mechanisms underlying one session of 50% MVC strength training with less-affected hand sheds light on a safe therapy. The study enhances our understanding of less-affected hand training and investigates the feasibility as a future rehabilitation approach. Analyzing how one session of 50% MVC strength training with less-affected hand affects brain activation and connectivity could lead to more tailored and effective rehabilitation strategies.