Translational Neuroscience最新文献

Episodic memory refers to the recall of memories concerned with unique, personal past experiences. It has been differentiated from semantic or rule learning that may be associatively learned. Episodic memory has the quality of mentally traveling back in time to recover a memory. Episodic memory is believed to be related to language and consciousness, and for this reason, has been thought to be unique to humans. Having episodic memory generally allows one to describe what happened, where it happened, and when it happened. For some time, research has focused on these three properties, and research with animals indicates that several species do have the capacity to behaviorally report the what, where, and when of an event. But such evidence is not sufficient to conclude that animals have episodic memory. Instead, to better distinguish episodic memory from semantic or rule learning, an organism should be able to respond appropriately to an unexpected question about an event that was incidentally rather than explicitly encoded. Using this criterion, there is growing evidence that several species do have such an ability. Furthermore, it is proposed that episodic memory serves to enable future planning, and animals show some evidence for that as well.

Objective: Intracranial infection is a serious complication after neurosurgery. However, the early diagnosis of post-neurosurgical intracranial infection (PNICI) remains challenging. The purpose of this study was to compare clinical characteristics and common laboratory indicators in patients with and without intracranial infections after neurosurgery and construct a diagnostic model of PNICI and assess its diagnostic efficacy.

Methods: A total of 623 patients who underwent neurosurgery from January 2018 to October 2021 were enrolled and divided into a training set and a validation set. SPSS 22.0 software was used to compare the differences in basic information and laboratory examination results between the two groups to screen out valuable indicators. Subsequently, a nomogram for the diagnosis of PNICI was established. Then, the receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis (DCA) were performed to evaluate the discriminative ability, consistency, and clinical usefulness of the nomogram.

Results: The diagnostic model of PNICI consisted of seven variables: meningeal irritation, fever, postoperative drainage, cerebrospinal fluid (CSF) white blood cells, CSF chlorine, the CSF/blood glucose ratio, and blood neutrophil percentage. The model achieved an area under the ROC curve of 0.958 in the training set and 0.966 in the validation set. At the optimal cutoff of 0.397, the training set demonstrated 90.4% sensitivity and 90.8% specificity. The calibration curves and DCA curves of the nomogram demonstrated that the model exhibited good goodness of fit and showed a net benefit from its use.

Conclusions: We developed an easily applicable nomogram using routinely available indicators. This tool enables early risk stratification for PNICI, facilitating timely interventions that may reduce infection-related complications. However, multicenter prospective validation data are required to further confirm the clinical utility.

Objective: Acute sleep deprivation (ASD) is prevalent in contemporary society. This study explored the mechanism of melatonin affecting cognitive dysfunction (CD) in ASD mice through the nuclear factor kappaB (NF-κB) pathway and oxidative stress.

Methods: The ASD mouse model was established and treated with low-dose and high-dose melatonin, a NF-κB inhibitor PDTC, or lipopolysaccharide (LPS), with their spatial memory, spontaneous activity, and anxiety assessed. Hippocampal morphology and neuronal status were observed via HE and Nissl staining. Superoxide dismutase (SOD) activity and levels of hippocampal CA1 region postsynaptic density protein 95 (PSD95), phosphorylated (p)-p65, and p-IκB proteins; acetylcholinesterase (AChE), acetylcholine (ACh), malondialdehyde (MDA), and reactive oxygen species (ROS); and IL-4, IL-10, tumor necrosis factor [TNF]-α, and IL-1β levels were determined by western blot and ELISA kits.

Results: ASD mice exhibited reduced learning and memory abilities and spontaneous activities, loosely-arranged cells in the hippocampal CA1 region, unclear cell body boundaries, enlarged gaps, severe neuronal damage, and reduced PSD95 protein level. There were increases in AChE, p-p65, p-IκB, TNF-α, IL-1β, MDA, and ROS levels, decrements in ACh, IL-4, and IL-10 levels and SOD activity in the hippocampal CA1 region of ASD mice. Melatonin or PDTC inhibited the NF-κB pathway, down-regulated TNF-α, IL-1β, MDA, and ROS and up-regulated IL-4 and IL-10 and SOD activity in the hippocampal CA1 region of ASD mice, and improved the learning and memory abilities. LPS-induced NF-κB pathway activation partially averted melatonin's beneficial effects on ASD mice.

Conclusion: Melatonin ameliorated ASD-induced CD in mice by modulating the NF-κB pathway and oxidative stress.

Objectives: Excessive neuroinflammatory responses represent a key pathological mechanism in cerebral small vessel disease (CSVD). Dl-3-n-butylphthalide (NBP), a compound previously demonstrated to possess anti-inflammatory properties in ischemic stroke, was investigated for its potential therapeutic effects in a rodent model of CSVD. This study aimed to elucidate the neuroprotective mechanisms of NBP in CSVD pathogenesis.

Methods: Forty-week-old spontaneously hypertensive rats were selected as a CSVD rodent model to determine the neuroprotective effects of NBP. Cognitive ability was assessed using the Morris water maze after 28 weeks of treatment. Pathological changes in the brain tissue were observed through immunohistochemistry. Data-independent acquisition (DIA) mass spectrometry was executed to identify the probable targets of NBP in CSVD. Based on the proteomics results, the expression of the toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway in the rat hippocampus was evaluated by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR).

Results: NBP treatment ameliorated the cognitive abilities and pathological changes in CSVD. DIA proteomics revealed 262 differentially expressed hippocampal proteins, with bioinformatics analysis highlighting acute inflammatory response as a primary target. Furthermore, western blotting and qRT-PCR results confirmed these results and showed that after treatment with NBP, TLR4 regulated NF-κB pathway and inflammatory factors decreased.

Conclusions: Our findings demonstrated that NBP exerts neuroprotection in CSVD probably by suppressing TLR4/MyD88/NF-κB-mediated neuroinflammation. This study provides the evidence of NBP's therapeutic mechanisms in CSVD, suggesting its potential as a targeted anti-inflammatory treatment.

Background: Multiple sclerosis (MS) is a major demyelinating disorder that affects the central nervous system. A growing body of evidence has revealed the involvement of coagulation pathway in the pathogenesis of MS. However, the causal association between coagulation factors and MS is still unclear.

Method: A two-sample Mendelian randomization (MR) analysis was conducted. Genetic variants for plasma coagulation factors were identified as instrumental variables. Summary-level statistics for MS were collected from a large-scale genome-wide association study, including 47,429 cases and 68,374 controls. Primary MR analysis was performed using the inverse-variance weighting (IVW) approach. False discovery rate (FDR)-adjusted method was applied to adjust for multiple testing. MR-Egger, weighted median, simple mode, weighted mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods were used as sensitivity analysis approaches.

Results: A causal effect of higher plasma tissue factor (TF) levels on the risk of MS onset was identified using IVW method (OR: 1.215, 95% CI 1.108-1.333, P < 0.001, P _FDR < 0.001). Complementary analysis using weighted median (OR: 1.262, 95% CI: 1.119-1.423, P < 0.001), weighted mode (OR: 1.238, 95% CI: 1.100-1.394, P = 0.012), and MR-PRESSO (OR: 1.215, 95% CI: 1.125-1.313, P = 0.003) methods yielded consistent results. Null associations were found for other plasma coagulation factors with MS.

Conclusions: The study demonstrates a suggestive association between TF and MS. Increasing plasma TF was associated with an increase in MS risk. TF should be a promising biomarker and new target for MS.

Objective: This study aims to determine if Lycium barbarum polysaccharides (LBP) extract attenuate oxidative stress by regulating the SIRT1/PGC-1α axis, potentially ameliorating oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal damage.

Methods: A cellular hypoxia/reoxygenation model (OGD/R) using HT22 cells was established to simulate cerebral ischemia-reperfusion injury. Cells were allocated into four groups: normal (Control), hypoxia (OGD/R), LBP extract-treated (OGD/R + LBP at 25, 50, 100 μg/mL), and SIRT1-inhibited (OGD/R + S100). Western blot and qPCR were performed to detect the expression of pathway-related factors, oxidative stress, mitochondrial function, and apoptosis-related factors.

Results: Compared to the Control group, the OGD/R group exhibited significantly reduced cell survival, increased LDH release, apoptosis rate, and reactive oxygen species (ROS) levels. After intervention with LBP extract, cell survival increased, LDH release, ROS levels, and apoptosis rates reduced. The above injuries were associated with the inhibition of the SIRT1/PGC-1α pathway. LBP extract can attenuate the hypoxia-reperfusion-induced inhibition of the SIRT1/PGC-1α pathway and reverse the resulting high levels of oxidative stress and apoptosis, ultimately ameliorating cellular injury.

Conclusion: LBP extract's protective effects against ischemia-reperfusion injury in HT22 cells appear linked to the modulation of the SIRT1/PGC-1α pathway and a reduction in oxidative stress.

Background: Depression is a pervasive neuropsychiatric disorder having significant social and economic impacts and often linked to imbalances in neurotransmitter systems. Traditional herbal medicines have garnered attention for their potential antidepressant effects, with limited research on Helianthus annuus (sunflower) as a therapeutic option.

Objectives: The present study was carried out to investigate the anti-depressant and neuromodulatory potential of hydroalcoholic extract of Helianthus annuus (H. annuus) florets in mouse models of depression.

Methods: Depression was induced in rats by the forced swim test (FST) and tail suspension test (TST). The hydroalcoholic extract of H. annuus was used as the test drug given in the doses of 200 and 400 mg/kg, whereas fluoxetine was used as the standard drug.

Results: The results revealed that the H. annuus extract decreased the immobility time significantly as reflected in FST and TST. Treatment with H. annuus extract also demonstrated significant improvement in the swimming and climbing times as reflected in FST. Administration of H. annuus extract significantly improved neurotransmitter levels such as serotonin, dopamine, and norepinephrine, which were significantly lowered in depression control rats. The mean value of thiobarbituric acid reactive substances was significantly lowered after the administration of H. annuus extract. Additionally, the levels of glutathione, superoxide dismutase, and catalase were significantly increased after the administration of H. annuus extract. Additionally, the mean value of inflammatory cytokines, for example, tumour necrosis factor alpha and interleukin-6 were reduced significantly in groups treated with H. annuus extract.

Conclusions: The results suggest that H. annuus extract exhibited significant antidepressant and neuromodulatory potential by ameliorating behavioural parameters, oxidative stress, and inflammatory markers.

Estradiol shapes systemic glucose homeostasis by action on ventromedial hypothalamic nucleus (VMN) targets. The neuropeptide transmitter growth hormone-releasing hormone (Ghrh) governs counterregulatory neurochemical marker mRNA expression in dorsomedial VMN (VMNdm) Ghrh/steroidogenic factor-1 (SF-1/Nr5a1) neurons. The current research used tools for in vivo gene silencing and single-cell laser catapult microdissection/multiplex qPCR to determine if VMN Ghrh receptor (Ghrh-R) regulates nuclear and/or membrane estrogen receptor (ER) gene transcription in those neurons. Intra-VMN Ghrh-R siRNA correspondingly up- or down-regulated baseline VMNdm Ghrh/SF-1 neuron ER-alpha (ERα) or G protein-coupled estrogen receptor-1 (GPER) transcripts in male rats; neither mRNA was affected by gene silencing in females. In each sex, hypoglycemic repression of these ER gene profiles was averted by Ghrh-R gene knockdown. Both sexes exhibited diminished baseline VMNdm Ghrh/SF-1 neuron ER-beta (ERβ) gene expression following Ghrh-R gene knockdown. ERβ mRNA was diminished (male) or unaffected (female) by hypoglycemia; Ghrh-R siRNA pretreatment enhanced transcript levels in hypoglycemic rats of either sex. Aromatase gene expression is higher in male versus female VMNdm Ghrh/SF-1 neurons and is inhibited by hypoglycemia in male rats alone. Ghrh-R gene knockdown augmented aromatase mRNA levels in each sex irrespective of glucose status. Results document glucose-dependent Ghrh-R control of VMNdm Ghrh/SF-1 neuron ERα (female), ERβ (both sexes), and GPER (both sexes) gene expression. Ongoing studies aim to characterize mechanisms that cause a hypoglycemia-associated gain of regulatory control or switch in direction (stimulatory-to-inhibitory) of control. Outcomes identify VMNdm Ghrh/SF-1 neurons as a putative neuroestradiol source in each sex and implicate Ghrh-R in hypoglycemic repression of this neurosteroid profile in males.

Parkinson's disease (PD) is increasingly understood as a neurodegenerative condition whose pathology extends beyond the direct and indirect basal ganglia pathways. Clinically, patients are all too painfully aware of dysfunction not only of motor circuits but also of somatosensory, autonomic, cognitive, and emotional systems. Functional neuroimaging studies have begun to document a functional reorganization in the PD brain across a wide number of networks. In particular, the cerebellar-thalamocortical, as well as the fronto-striatal circuit, have been shown to undergo functional reorganization. In this narrative review, citing preclinical as well as clinical neuroimaging studies, our objective is to highlight trends and discuss the relevance of cerebral adaptive changes. It remains clear that not all changes contribute to the normalization of functions. Parsing differences between functional "compensation," "silencing," or "maladaptation" in neural circuits is important. A necessary next step in neurorehabilitation is the question of whether compensatory cerebral changes can be enhanced. In this regard, physical exercise remains of interest, given that in patients, exercise may allow some degree of symptom improvement and possibly slow the course of the disease. Future interventions may wish to integrate neuroimaging findings as potential targets to support neuroplastic changes.