Journal of integrative neuroscience最新文献

Cognitive behavioral therapy for insomnia (CBT-I) is a widely used psychological intervention known for its effectiveness in improving insomnia symptoms. However, the neurophysiological mechanisms underlying the cognitive-behavioral treatment of insomnia remain unclear. This narrative review aimed to elucidate the neurophysiological and molecular mechanisms of CBT-I, focusing on the fields of psychology, neurophysiology, neuroendocrinology, immunology, medical microbiology, epigenetics, neuroimaging and brain function. A comprehensive search was conducted using databases including: PubMed, Embase, PsycINFO and Web of Science, with customized search strategies tailored to each database that included controlled vocabulary and alternative synonyms. It revealed that CBT-I may have a beneficial effect on the central nervous system, boost the immune system, upregulate genes involved in interferon and antibody responses, enhance functional connectivity between the hippocampus and frontoparietal areas and increase cortical gray matter thickness. In conclusion, an integrated model is proposed that elucidates the mechanisms of CBT-I and offers a new direction for investigations into its neurophysiological mechanisms.

Background: The aim of this study was to investigate the possible molecular mechanisms underlying cerebral small vessel disease caused by a missense mutation in the high-temperature serine peptidase A1 gene, HtrA1 (NM_002775.4, Exon4, c.905G>A, p.Arg302Gln). Stable strain models were constructed using wild-type and mutant HtrA1 overexpression lentiviral vectors to infect mouse brain microvascular endothelial cells (bEnd.3 cells).

Methods: HtrA1 mRNA and protein expression were analyzed by Western blot and quantitative real-time polymerase chain reaction. Western blot technique was also used to evaluate the expression of transforming growth factor (TGF)-β/Smads-related signaling pathway proteins and the oxidative stress pathway protein nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). The level of reactive oxygen species (ROS) was evaluated using dichloro-dihydro-fluorescein diacetate (DCFH-DA) fluorescent probes.

Results: HtrA1 mRNA and protein expression levels were found to be decreased in mutant cells, whereas the levels of ROS, the TGF-β/Smads proteins, and the caspase3 and cleaved-caspase3 apoptotic proteins were increased.

Conclusions: Lentivirus-mediated missense mutation in HtrA1 leads to activation of the TGF-β/Smads pathway and to increased apoptosis of mouse brain microvascular endothelial cells via the oxidative stress pathway. Further in vivo studies are required to explore the connections between different signaling pathways in animals, and to identify potential molecular targets for clinical therapy.

Objective: Consuming soy in the diet is beneficial for health, and tofu possess the richest source of dietary soy. However, the specific association with stroke and related subtypes remains controversial. In this study, the genetic causal relationship among tofu and stroke as well as the subtypes was investigated by utilizing the data in a number of genome-wide association study (GWAS) based on population.

Methods: The tofu intake GWAS analysis is derived from the Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol (MRC-IEU) Consortium. The two-sample Mendelian randomization (MR) study was carried out, utilizing multiple analysis methods to analyze the associations with stroke and related subtypes. The sensitivity, heterogeneity, and potential pleiotropy could be investigated by multiple analysis method.

Results: We found that tofu intake had no causal relationship with stroke. However, in stroke subtype, there is a causal relationship among tofu intake with the risk of intracerebral hemorrhage (ICH) (odds ratio, OR = 1.24 × 10^-5, 95% CI: 1.54 × 10^-8-9.95 × 10^-3, p = 9.300 × 10^-4), while tofu intake does not affect the risk of ischemic stroke (OR = 1.07 × 10^-1, 95% CI: 3.84 × 10^-4-2.97 × 10¹, p = 4.362 × 10^-1) and subarachnoid hemorrhage (SAH) (OR = 3.33 × 10^-3, 95% CI: 1.79 × 10^-6-6.18, p = 1.373 × 10^-1). Both the Mendelian randomization PRESSO (MR-PRESSO) global test and Cochran's Q test did not detect any sensitivity and heterogeneity.

Conclusions: While tofu consumption is associated with a higher risk of ICH, it does not show a significant relationship with ischemic stroke or SAH. The varying effects of tofu on different stroke subtypes underscore the need for considering potential confounding dietary and lifestyle factors in future studies.

Background: Avicularin (AL), an ingredient of Banxia, has anti-inflammatory properties in cerebral disease and regulates polarization of macrophages, but its effects on ischemic stroke (IS) damage have not been studied.

Methods: In vivo, AL was administered by oral gavage to middle cerebral artery occlusion/reperfusion (MCAO/R) C57BL/6J mice in doses of 1.25, 2.5, and 5 mg/kg/day for seven days, and, in vitro, AL was added to treat oxygen-glucose deprivation (OGD)-BV2 cells. Modified neurological severity score, Triphenyltetrazolium chloride (TTC) staining, brain-water-content detection, TdT-mediated dUTP nick-end labeling (TUNEL) assay, flow cytometry, immunofluorescence assay, Enzyme linked immunosorbent assay (ELISA), and Western-blot analysis were used to investigate the functions and mechanism of the effect of AL treatment on IS. The exosomes of AL-treated microglia were studied by transmission electron microscope (TEM), nanoparticle tracking analyzer (NTA), and Western-blot analysis.

Results: AL treatment reduced the neurological severity score, infarct volume, brain-water content, neuronal apoptosis, and the release of inflammatory factors, that were induced by MCAO/R. Notably, M2 microglia polarization was promoted but M1 microglia polarization was inhibited by AL in the ischemic penumbra of MCAO/R mice. Subsequently, anti-inflammatory and polarization-regulating effects of AL were verified in vitro. Suppressed NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation was found in the ischemic penumbra of animal and Oxygen-Glucose Deprivation/Reoxygenation (OGD/R) cells treated with AL, as evidenced by decreasing NLRP3-inflammasome-related protein and downstream factors. After AL treatment, the anti-apoptosis effect of microglial exosomes on OGD/R primary cortical neurons was increased.

Conclusion: AL reduce inflammatory responses and neuron death of IS-associated models by regulating microglia polarization by the NLRP3 pathway and by affecting microglial exosomes.

Alzheimer's disease (AD) is the most common cause of dementia. The two major hallmarks of this disease are extracellular amyloid plaques and intracellular neurofibrillary tangles in the brain, accompanied by loss of neurons and synapses. The plaques and tangles mainly consist of amyloid-β (Aβ) and tau protein, respectively. Most of the therapeutic strategies for AD to date have focused on Aβ. However, there is still no effective therapy available. In recent years, the clinical therapeutic failure of targeting Aβ pathology has resulted in increased interest towards tau-based therapeutics. In the current review, we focus on the research progress regarding the pathological mechanisms of tau protein in this disease and discuss tau-targeting therapeutic strategies.

Background: Despite the connections and clear importance of the cerebellum in motor function, research utilizing cerebellar neuromodulation for treatment of movement disorders is still underdeveloped. Here we conduct a systematic review to investigate non-invasive neurostimulation of the cerebellum and its potential impact on motor systems and its function. Our aim is to give a general review of each neurostimulation study focusing on the cerebellum as a treatment target in the past five years at time of search, in order to update the field on current findings and inspire similar cerebellar neurostimulation research without unnecessary repetition.

Methods: Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, our search included articles over the past five years that evaluated neurostimulation of the cerebellum (e.g., transcranial magnetic stimulation, transcranial direct current stimulation, and transcranial alternating current stimulation, etc.). Inclusion criteria included: (1) neurostimulation (repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS)) of the cerebellum; (2) only original articles, and (3) outcomes focused on motor functions. Exclusion criteria included: (1) neurostimulation with the goal of targeting any brain structure other than the cerebellum and (2) reviews and conference abstracts.

Results: The search revealed 82 distinct articles relevant to the research question. Included are 17 articles concerning rTMS, 56 articles concerning tDCS, and 9 articles concerning tACS. The majority of the studies are controlled trials of varying types, with 79, with two case studies and one pilot study.

Conclusions: Many studies showed significant effects on motor function and circuitry via non-invasive neurostimulation of the cerebellum. Common targets of cerebellar neurostimulation include visuomotor control, stroke rehabilitation for improvements in balance and coordination, and motor skill acquisition. The field is still exploring ideal parameters of neurostimulation for each disorder or function of interest. Future research areas should include the inclusion of individual anatomy, including functional connectivity, and improving stimulation selectivity.

Purpose: Alzheimer's disease (AD) is characterized by cognitive decline and abnormal protein accumulation. Copper imbalance and pyroptosis play significant roles in the pathogenesis of AD. Recent studies have suggested that dysregulated copper homeostasis contributed to β-amyloid accumulation, which may activate the NOD-like receptor protein 3 (NLRP3)-related pyroptosis pathway, promoting neuronal damages and AD progression. Therefore, the present study aims to investigates whether copper facilitates AD through exacerbating β-amyloid (Aβ) induced activation of NLRP3/Caspase-1/Gasdermin D (GSDMD)-mediated neuronal cell pyroptosis.

Methods: Mouse hippocampal HT-22 cells were cultured with Aβ1-42 oligomer for 24 h as AD Model group. CuCl₂ treatment was administered to the AD cell model, and cell survivability levels were detected by Cell Counting Kit-8 (CCK-8), TdT-mediated dUTP nick end labeling (TUNEL), and other relevant kits. Mitochondrial function was evaluated using Mitochondrial membrane potential dye JC-1 and transmission electron microscopy (TEM). After intervention with the NLRP3 inhibitor MCC950, activation of the NLRP3/Caspase-1/GSDMD pathway by copper ions (Cu²⁺) was confirmed via Western Blot. Thioredoxin T (ThT) fluorescence assay was performed to observe the aggregation effect of Aβ induced by Cu²⁺ overload.

Results: CuCl₂ treatment of the AD cell model resulted in up-regulation of the levels of Lactate Dehydrogenase (LDH), Interleukin-1β (IL-1β), and IL-18 expression, which indicated activation of pyroptosis. We observed a significant decrease in mitochondrial membrane potential, mitochondrial swelling, and loss of mitochondrial cristae by fluorescence microscopy and TEM. ThT fluorescence imaging showed that Cu²⁺ promoted Aβ aggregation and up-regulated NLRP3, apoptosis-associated speck-like protein containing a CARD (ACS), Caspase-1, Cleaved Caspase-1, GSDMD, and Gasdermin D N-terminal (GSDMD-NT). The NLRP3 inhibitor MCC950 partially reversed Cu²⁺-mediated pyroptosis in HT-22 cells.

Conclusions: Exposure to copper ions disrupt mitochondrial copper homeostasis, promotes Aβ aggregation, and activates NLRP3 inflammasomes, further promoting the Aβ aggregation activated pyroptosis in AD cell models.

Intracranial vascular-related diseases are a common occurrence in neurosurgery. They have complex and diverse pathogeneses; further, their diagnosis and treatment remain unclear. Three-dimensional image post-processing technology is an emerging technology that involves converting a brain image scan into a digital model using image post-processing software, thus establishing a 3D view of the region of interest. Three-dimensional visualisation of the brains of patients with cerebrovascular diseases can allow a more intuitive examination of the local anatomy of the lesion as well as the adjacency between the lesion and peripheral nerves, brain tissue, and skull bones. Subsequently, this informs pre-operative planning, allows more accurate diagnosis of cerebrovascular diseases, and improves the safety of surgical treatment. This review summarised the current literature regarding cerebrovascular diseases and the application of 3D image post-processing technology in different cerebrovascular diseases.

Background: Acute gamma-aminobutyric acid (GABAergic) effects of alcohol consumption are well-known, whereas prior research has yielded inconsistent findings regarding on adaptations of the GABAergic neurotransmitter system to chronic alcohol use. Previous studies indicate either elevated or reduced GABA levels in cortical regions such as the anterior cingulate cortex (ACC) in persons with alcohol use disorder (AUD). We tested the hypothesis that active alcohol consumption compared to abstinence contributes to GABA levels as observed in prior research on chronic alcohol use.

Methods: We investigated GABA levels in the ACC of 31 healthy controls (low risk, LR), 38 high risk individuals providing an active drinking pattern (high risk, HR) and 27 recently detoxified alcohol-dependent (AD) subjects via proton magnetic resonance spectroscopy (1H-MRS).

Results: GABA levels in the ACC were significantly lower in HR compared with AD, but did neither differ between LR and AD nor between LR and HR. Also, we observed a quadratic effect indicating a distribution of GABA levels in the ACC as follows: LR > HR < AD. GABA levels were not associated with abstinence duration in AD.

Conclusions: This study suggests that the GABAergic neurotransmitter system is blunted in AUD. More precisely GABA levels in the ACC seem to be higher in recently detoxified AD patients than in individuals at high risk which might suggest that GABA levels may increase after abstinence. No correlation was found between GABA levels and abstinence duration. Longitudinal studies are required to investigate alterations in the GABAergic system throughout the development and maintenance of AUD.

Clinical trial registration: No: NCT02094196. Registered 20 March 2014, https://clinicaltrials.gov/study/NCT02094196.

Background: Many studies have shown that total sleep deprivation (TSD) impairs the attention network, which includes three subcomponents as follows: alerting, orienting, and executive control. However, the specific attention network(s) damaged by TSD remains unclear.

Methods: Twenty two participants were enrolled to complete the attention network test (ANT) before and after 36 h of TSD with simultaneous electroencephalography recordings.

Results: The repeated-measures analysis of variance of the response time (RT) suggested that the interaction effect between sleep conditions (before versus after TSD) and target congruence (incongruent versus congruent target) was significant; that is, the RT of the incongruent target was longer than that of the congruent target, whereas this difference disappeared after TSD. Furthermore, the interaction effect of sustained potential (SP) amplitude between the sleep conditions and target congruence was significant; that is, the incongruent target invoked a less positive sustained potential amplitude after than before TSD; whereas that invoked by the congruent target was not.

Conclusion: TSD selectively impairs attention networks. TSD affects the executive control network the most, which is followed by the alerting network rather than the orienting network. This provides a new perspective for understanding how shortened sleep affects attention.

Clinical trial registration: No: ChiCTR2400088448. Registered 19 August 2024, https://www.chictr.org.cn.