Journal of integrative neuroscience最新文献

Background: The goal of these experiments was to determine which learning and memory system(s) were necessary for the retention of visual discriminations and subsequent acquisition of a second problem. The dorsal striatum should be involved in the acquisition and expression of this task based on previous work implicating this region in instrumental learning and memory processes. The perirhinal cortex has been implicated in learning and memory processes associated with visual information like objects, and pictures and may also play a role in the acquisition and/or retention of visual discriminations. As there is no clear spatial/relational component to the task, the hippocampus should not be involved.

Methods: Rats were trained on a two-choice visual discrimination task to criterion performance after which they received lesions to portions of the dorsal striatum (dorso-medial or dorso-lateral striatum) and medial temporal lobe (perirhinal cortex or hippocampus). After surgical recovery, the rats were tested for retention of the original discrimination, followed by training on a second problem on the same task.

Results: The results showed that dorsal medial striatal lesions produced a retrograde deficit on picture discrimination, but dorsal lateral striatum lesions did not. Neither dorsal striatal lesion produced a deficit on acquisition of a second problem. Perirhinal cortex did not seem to make an essential contribution to the retention of the original discrimination or acquisition of the second problem. Surprisingly, subjects with hippocampal damage were severely impaired but eventually re-learned the discrimination. Damage to the hippocampus had no impact on acquisition of a second problem.

Conclusions: Taken together, the results of the present experiments show that the dorsomedial striatum and the hippocampus may support performance on this instrumental task if intact during acquisition but is not required for acquisition of a new problem. The implications of this pattern of results for our understanding of the organization of learning and memory in mammals is discussed.

Background: Parkinson's disease (PD) is currently the second most common degenerative neurological disorder globally, with aspiration pneumonia caused by difficulty swallowing being the deadliest complication. The patient's subjective experience and the safety of swallowing have been the main focus of previous evaluations and treatment plans. The effectiveness of treatment may be attributed to the brain's ability to adapt and compensate. However, there is a need for more accurate assessment methods for dysphagia and further research on how treatment protocols work.

Objective: This systematic review was designed to assess the effectiveness and long-term impact of published treatment options for swallowing disorders in patients with PD.

Methods: In adherence to the Preferred Reporting Items for Reviews and Meta-analysis (PRISMA) guidelines, we conducted a systematic review where we thoroughly searched multiple databases (PubMed, Web of Science, Elsevier, and Wiley) for clinical studies published in various languages until December, 2023. Two reviewers evaluated the studies against strict inclusion/exclusion criteria.

Results: This systematic review included a total of 15 studies, including 523 participants, involving six treatment approaches, including breath training, deep brain stimulation, reduction of upper esophageal sphincter (UES) pressure, transcranial magnetic stimulation, postural compensation, and video-assisted swallowing therapy. Primary outcomes included video fluoroscopic swallowing study (VFSS), fiberoptic endoscopic evaluation of swallowing (FEES), high-resolution pharyngeal impedance manometry (HPRIM), and functional magnetic resonance imaging (fMRI).

Conclusion: Treatments that reduce UES resistance may be an effective way to treat dysphagia in PD patients. HRPIM can quantify pressure changes during the pharyngeal period to identify patients with reduced swallowing function earlier. However, due to the limited number of randomized controlled trials (RCTs) included and the high risk of bias in some studies, large-scale RCTs are needed in the future, and objective indicators such as HRPIM should be used to determine the effectiveness and long-term impact of different therapies on dysphagia in PD patients.

Glial cells, including astrocytes and microglia, are pivotal in maintaining central nervous system (CNS) homeostasis and responding to pathological insults. This review elucidates the complex immunomodulatory functions of glial cells, with a particular focus on their involvement in inflammation cascades initiated by the accumulation of alpha-synuclein (α-syn), a hallmark of Parkinson's disease (PD). Deriving insights from studies on both sporadic and familial forms of PD, as well as animal models of PD, we explore how glial cells contribute to the progression of inflammation triggered by α-syn aggregation. Additionally, we analyze the interplay between glial cells and the blood-brain barrier (BBB), highlighting the role of these cells in maintaining BBB integrity and permeability in the context of PD pathology. Furthermore, we delve into the potential activation of repair and neuroprotective mechanisms mediated by glial cells amidst α-syn-induced neuroinflammation. By integrating information on sporadic and familial PD, as well as BBB dynamics, this review aims to deepen our understanding of the multifaceted interactions between glial cells, α-syn pathology, and CNS inflammation, thereby offering valuable insights into therapeutic strategies for PD and related neurodegenerative disorders.

Introduction: This research aimed to investigate the pathophysiological mechanism of how drug-induced parkinsonism (DIP) affects the integrity of the white matter (WM) fiber microstructure as measured by magnetic resonance diffusion tensor image (DTI) fractional anisotropy (FA) and mean diffusivity (MD).

Methods: We recruited 17 participants diagnosed with DIP, 20 Parkinson's disease (PD) patients, and 16 normal controls (NCs) with a similar age, gender, and years of education. Subsequently, all participants underwent DTI magnetic resonance imaging scanning. To analyze the data, we utilized the software packages Functional MRI of the Brain Centre (FMRIB) Diffusion Toolbox (FDT), developed by the FMRIB laboratory at Oxford University, and tract-based spatial statistics (TBSS).

Results: The Argentina Hyposmia Rating Scale (AHRS) scores of patients in DIP group were markedly higher than those in PD patients group. Compared with the NC group, the FA values in the genu and body of the corpus callosum (CC), anterior limb of the right internal capsule, bilateral anterior corona radiata, bilateral superior corona radiata, right external capsule, and right superior fronto-occipital fasciculus (could be a part of the anterior internal capsule) were significantly decreased in the DIP group; however, no significant cluster was found in MD.

Conclusions: The present study provides novel insights into the alterations in WM microstructure among DIP patients, suggesting that these methodologies have the potential to aid in the early diagnosis and treatment of DIP.

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.