Neuroscience最新文献

Focal Cortical Dysplasia (FCD) & Mesial Temporal Lobe Epilepsy-Hippocampal Sclerosis (MTLE-HS) are two common pathologies of drug-resistant focal epilepsy (DRE). Inappropriate localization of the epileptogenic zones (EZs) in FCD is a significant contributing factor to the unsatisfactory surgical results observed in FCD cases. Currently, no molecular or cellular indicators are available which can aid in identifying the epileptogenic zones (EZs) in FCD. Phospholipid modifications in healthy and malignant tumour tissues have been documented and used to demarcate tumour boundaries. The objective of this research was to analyze and evaluate the lipid profiles in a manner that takes into account the specific disease and subtype. The technique of liquid chromatography and tandem mass spectrometry was utilized to detect changes in lipids in surgically resected brain samples from patients with FCD and MTLE-HS, in comparison to non-epileptic controls. Significant upregulation of TAGs was seen in both FCD and MTLE-HS. Additionally, the levels of triglycerides in the plasma of peripheral blood were measured in patients with FCD, MTLE-HS, and healthy individuals as controls. These findings suggest that employing distinct lipid mass spectra could be an effective method for identifying the EZs in FCD. The unique lipid mass spectra of cortical tissues from patients with FCD can be utilized for real-time surgical guidance. Additionally, the plasma triglyceride (TAG) level has the potential to act as a biomarker once validated on a larger cohort.

Apelin, an endogenous ligand of G protein-coupled receptor APJ, is widely distributed in the central nervous system (CNS). It can be divided into such subtypes as Apelin-13, Apelin-17, and Apelin-36 as they have different amino acid structures. All Apelin is widely studied as an adipokine, showing a significant protective effect through regulating apoptosis, autophagy, oxidative stress, angiogenesis, inflammation, and other pathophysiological processes. As an adipokine, Apelin has been found to play a crucial role in cardiovascular disease development. In this paper, we reviewed the effects and mechanisms of Apelin in treating CNS diseases, such as neurotrauma, stroke, spinal cord injury, primary tumors, neurodegenerative diseases, psychiatric diseases, epilepsy, and pain.

Objectives: The association of neuroticism and cerebral small vessel disease (CSVD) development remains unclear. In this study, we used Mendelian randomization (MR) to explore the potential role of neuroticism in CSVD development.

Methods: We collected data on ischemic stroke (IS); small vessel stroke (SVS); three neuroimaging markers altered in CSVD, including white matter hyperintensity (WMH), fractional anisotropy (FA), and mean diffusivity (MD); and three neuroticism clusters, including depressed affect, worry, sensitivity to environmental stress and adversity (SESA), from large-scale genome-wide association studies (GWAS). Bidirectional MR analyses were used to evaluate the association between neuroticism and CSVD, primarily estimated using the inverse variance weighted (IVW) method. The linkage disequilibrium score (LDSC) regression was employed to assess the association between various phenotypes.

Results: LDSC analysis unveiled a noteworthy genetic correlation between depressed affect and IS (rg = 0.111, p = 0.001) as well as between worry and SVS (rg = -0.111, p = 0.032). Our study revealed a causal correlation between SESA and FA using both forward and reverse MR analyses (SESA on FA, odds ratio (OR) = 0.186 (0.071 to 0.483), p = 5.50 × 10^-4; FA on SESA, OR = 0.996 (0.9916 to 0.9997), p = 0.035). Meanwhile, FA also exerted a statistical causal influence on depressed affect cluster (OR = 0.992 (0.987 to 0.997), p = 0.001).

Interpretation: This research suggests a potential correlation between certain aspects of neuroticism and CSVD, with further studies needed to better understand the causal relationship and its implications for patient intervention.

Hypothyroidism is known to affect memory consolidation, and our prior research highlighted the potential of chrysin as a therapeutic agent to restore cognitive function. The present study aimed to investigate the action mechanism of chrysin on memory deficits in hypothyroid in C57BL/6 female mice. We assessed cognitive flexibility, declarative, working, and aversive memories while analyzing the BDNF/TrkB/AKT/Creb neuroplasticity signaling pathway and synaptic function in the hippocampus and prefrontal cortex. To induce hypothyroidism, mice were exposed to 0.1 % methimazole (MTZ) in the drinking water for 31 days. After confirming low thyroid hormones levels, the mice received either vehicle or chrysin (20 mg/kg) intragastrically once a day for 28 consecutive days. Memory tests were conducted in two separate experiments (experiment 1: Y-maze and reverse Morris water maze; experiment 2: object recognition task and step-down latency), ensuring no memories overlap. Following the tests, the brain samples were collected to analyses ex vivo. Hypothyroid mice exhibited deficits in cognitive flexibility and various memory types, along with altered protein expression related to the BDNF/TrkB/Creb signaling pathway and increased AKT levels in hippocampus and prefrontal cortex. Chrysin treatment effectively reversed these memory deficits, restored cognitive flexibility, and improved protein levels. Our findings suggest that hypothyroidism impairs cognitive flexibility and memory through the BDNF/TrkB/AKT/Creb pathway, which chrysin modulates, operating as a neuroprotector in hypothyroidism. This research sheds light on the potential therapeutic benefits of chrysin for memory-related issues in hypothyroidism.

The aim of this study was to assess the potential causal relationship between lifestyle factors and intracranial aneurysms (IAs) using a two-sample Mendelian randomization (MR) approach. The study used a pooled dataset from a genome-wide association study that covered information on 24 lifestyle factors, intracranial aneurysm cases, subarachnoid hemorrhage, and unruptured aneurysms. Five MR methods were applied for analysis by selecting single nucleotide polymorphisms as instrumental variables, with the inverse variance weighting method as the main method. To ensure the stability of the results, horizontal multiple validity tests, sensitivity analyses, and inverse MR were performed, and genetically determined exposure factors were adjusted by multivariate MR. Several lifestyle factors were found to have a significant genetic causal effect on the occurrence and development of intracranial aneurysms. For example, lamb intake, smoking initiation, number of cigarettes smoked per day, length of television viewing, and fatigue were identified as genetic risk factors and strongly associated with aneurysm rupture, whereas red wine intake showed some genetic protection against intracranial aneurysms and similarly affected aneurysm rupture. Sensitivity analyses and inverse MR verified the robustness of these results. After adjusting for exposure factors, multivariate MR confirmed daily smoking and smoking initiation as risk factors for intracranial aneurysms, unruptured aneurysms, and subarachnoid hemorrhage, whereas red wine intake was a genetically protective factor against intracranial aneurysms and subarachnoid hemorrhage. This MR analysis revealed a genetic causal link between specific lifestyle factors and intracranial aneurysms, emphasizing the need for further studies to confirm these findings and explore their mechanisms.

Metabotropic glutamate receptors (mGluRs) are widely expressed throughout the central nervous system. They are linked to G-protein coupled receptors and are known to modulate synaptic transmission. The data regarding their expression in auditory structures are not systematic and mainly originate from physiological studies where expression was used to support physiological findings. MGluRs are classified into three groups based on their sequence homology, G protein-coupling, and ligand selectivity. Our recent physiological findings made us focus on the group II mGluRs. The objective of this study was to characterize group II mGluR expression, and whether it changes in aged brains, in three central auditory structures: inferior colliculus (IC), medial geniculate body (MG), and auditory cortex (AC). We performed immunostaining experiments followed by optical density quantification in young and old mice. We found group II mGluR staining in the IC, MG, and AC. However, the intensity of this staining was not uniform within these auditory structures. In the IC expression was more intense in the dorsal compared to ventral part. Contrarily, the staining was more pronounced in the ventral part of the MG. In the AC, the staining was more intense near the surface and diminished toward white matter. We also found that the overall expression level of mGluR2/3 was increased significantly in aged animals in all auditory structures tested. Collectively, our detailed immunostaining findings suggest that the group II mGluRs are widely expressed throughout the central auditory system and their contribution to auditory processing increases with age.

The optimal stimulation frequency for inducing neuromodulatory effects remains unclear. The purpose of our study was to investigate the effect of neuromuscular electrical stimulation (NMES) with different frequencies on cortical and spinal excitability. Thirteen able-bodied individuals participated in the experiment involving NMES: (i) low-frequency at 25 Hz, (ii) high-frequency at 100 Hz, and (iii) mixed-frequency at 25 and 100 Hz switched every one second. All interventions were applied on the tibialis anterior muscle using a 10 sec ON / 10 sec OFF duty cycle for 10 min, using motor-level NMES at 120 % of the individual motor threshold for each stimulating frequency. Assessments were performed at baseline, immediately after, and 30 min after the interventions. Corticospinal excitability and intracortical inhibition were examined using transcranial magnetic stimulation by assessing the motor evoked potentials and cortical silent period, respectively. Spinal motoneuron excitability and neuromuscular propagation were assessed using peripheral nerve stimulation by evaluating F-wave and maximum motor (M_max) responses, respectively. Maximal voluntary contraction (MVC) was evaluated during isometric dorsiflexion force exertion. Motor performance was also evaluated during the ankle dorsiflexion force-matching task. Our results showed that mixed frequency was most effective in modulating corticospinal excitability, although motor performance was not affected by any intervention. The cortical silent period was prolonged and M_max was inhibited by all frequencies, while the F-wave and MVC were unaffected. Mixed-frequency stimulation could recruit a more diverse range of motor units, which are recruited in a stimulus frequency-specific manner, than single-frequency stimulation, and thus may have affected corticospinal facilitation.

Myelination is the process by which oligodendrocytes ensheathe 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.

Vascular obstruction often causes inadequate oxygen and nutrient supply to the brain. This deficiency results in cerebral ischemic injury, which significantly impairs neurological function. This review aimed to explore the neuroprotective and regenerative effects of nerve growth factor (NGF) in cerebral ischemic injury. NGF, a crucial neurotrophic factor, could inhibit neuronal apoptosis, reduce inflammatory responses, and promote axon regeneration and angiogenesis through its interaction with TrkA, a high-affinity receptor. These functions were closely related to the activation of Phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) and Mitogen-Activated Protein Kinase (MAPK) pathways. Moreover, the mechanisms of NGF in the acute and recovery phases, along with the strategies to enhance its therapeutic effects using delivery systems (such as intranasal administration, nanovesicles, and gene therapy) were also summarized. Although NGF shows great potential for clinical application, its delivery efficiency and long-term safety still need more research and improvements. Future research should focus on exploring the specific action mechanism of NGF, optimizing the delivery strategy, and evaluating its long-term efficacy and safety to facilitate its clinical transformation in cerebral ischemic stroke.

Alzheimer's disease (AD) is a growing health problem worldwide, particularly in the developed world due to an ageing population. Glutamate excitotoxicity plays a major role in the pathophysiology of AD, and glutamate re-uptake is controlled by excitatory amino acid transporters (EAATs). The EAAT2 isoform is the predominant transporter involved in glutamate reuptake, therefore EAAT1 has not been the focus of AD research. We investigated the layer-specific expression of EAAT1 in human medial temporal lobe regions such as the hippocampus, subiculum, entorhinal cortex and superior temporal gyrus, using fluorescent immunohistochemistry and laser scanning confocal microscopy in human post-mortem tissue. We observed low EAAT1 immunoreactivity in control cases, but upregulated labeling in AD across several brain regions of the medial temporal lobe. Significantly higher integrated density in AD cases was observed in the str. oriens and str. radiatum of the CA2 region, the str. pyramidale of CA3, and the str. moleculare and str. granulosum of the DG. Labeling of EAAT1 appeared astrocytic in nature, showing close association with astrocytic processes in AD cases. We also report that a higher EAAT1 density was positively correlated with the age of AD cases, but this relationship was not observed in control cases. Overall, our results indicate an upregulation of EAAT1 across several hippocampal subregions and layers in AD cases, indicating a potential physiological role for this transporter that needs further investigation.