Brain Research最新文献_第4页

Role of dexmedetomidine in postoperative cognitive dysfunction and sleep improvement in aged rats by regulating the PI3K/Akt signaling pathway and its mechanism

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-30 DOI: 10.1016/j.brainres.2025.149482

Ying Kong , Xiaopeng Wang , Jun Pang , Haiyan Huo , Xiaofang Wang

Objective

This study aims to explore the mechanism of dexmedetomidine (Dex) in improving postoperative cognitive dysfunction (POCD) and postoperative sleep in aged rats through the PI3K/Akt signaling pathway.

Methods

Splenectomy was used to establish a POCD model in aged rats. Open field test (OFT) and new object recognition test (NORT) were used to observe the cognitive function of rats The awakening and sleep times of rats were recorded. Hematoxylin-eosin, Nissl, and TUNEL staining were adopted to examine histopathological alterations, neuronal cell damage, and apoptosis, respectively; western blot to detect the activation of the PI3K/Akt signaling pathway and the protein level of apoptosis factors Bcl-2, Bax, and cleaved caspase-3; enzyme-linked immunosorbent assay to quantify the concentrations of inflammatory factors IL-6, IL-1β, and TNF-α.

Results

On days 1, 7, and 14 post-splenectomy surgery, aged rats exhibited shortened moving distance in OFT, reduced discrimination rate in NORT, prolonged awakening time, and shortened sleep time, while such effect was reversed by further Dex treatment. In addition, neuronal damage, inflammatory response, and apoptosis occurred in the hippocampal CA1 area in aged rats but can be attenuated by Dex treatment. Dex triggered the activation of the PI3K/Akt signaling pathway in the hippocampus in aged rats after surgery, and inhibition of the PI3K/Akt signaling pathway can result in a partial reversal of the alleviating effects observed with Dex treatment.

Conclusion

Dex improves POCD and postoperative sleep in aged rats by activating the PI3K/Akt signaling pathway to reduce inflammatory response and apoptosis in the hippocampal CA1 area.

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引用次数: 0

Happy and angry facial expressions are processed independently of task demands and semantic context congruency in the first stages of vision – A mass univariate ERP analysis

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-29 DOI: 10.1016/j.brainres.2025.149481

Calla Mueller, Amie J. Durston, Roxane J. Itier

Neural decoding of others’ facial expressions is critical in social interactions and has been investigated using scalp event related potentials (ERPs). However, the impact of task and emotional context congruency on this neural decoding is unclear. Previous ERP studies employed classic statistical analyses that only focused on specific electrodes and time points, which inflates type I and type II errors. The present study re-analyzed the study by Aguado et al. (2019) using robust data-driven Mass Univariate Statistics across every time point and electrode and rejected trials with early reaction times to rule out motor-related activity on neural recordings. Participants viewed neutral faces paired with negative or positive situational sentences (e.g. “She catches her partner cheating on her with her best friend”), followed by the same individuals’ faces expressing happiness or anger, such that the facial expressions were congruent or incongruent with the situation. Participants engaged in two tasks: an emotion discrimination task, and a situation-expression congruency discrimination task. We found significant effects of expression largest during the N170-P2 interval, and effects of congruency and task around an LPP-like component. However, the effect of congruency was significant only in the congruency task, suggesting a limited and task-dependant influence of semantic context. Importantly, emotion did not interact with any factor neurally, suggesting facial expressions were decoded automatically during the first 400 ms of vision, regardless of context congruency or task demands. The results and their discrepancies with the original findings are discussed in the context of ERP statistics and the replication crisis.

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引用次数: 0

Senescent microglia: The hidden culprits accelerating Alzheimer’s disease

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-28 DOI: 10.1016/j.brainres.2025.149480

Wu Li , Xie Yong-Yan , Mu Jia-Xin , Ge Shu-Chao , Huang Li-Ping

Ageing is a major risk factor for neurodegenerative diseases like Alzheimer’s disease (AD). Microglia, as the principal innate immune cells within the brain, exert homeostatic and active immunological defense functions throughout human lifespan. The age-related dysfunction of microglia is currently recognized as a pivotal trigger for brain diseases associated with aging. In AD, microglia exhibit alterations in gene expression, cellular morphology, and functional behavior. By focusing on the immunomodulatory functions of factors secreted by senescent microglia, such as cytokines, chemokines, complement factors, and reactive oxygen species (ROS), we explore the diverse detrimental effects of microglia in aging and AD pathogenesis, including Aβ accumulation, Tau deposition, synaptic dysfunction, and neuroinflammation. These collectively contribute to hastening the progression of. In this review, we highlight the key role of senescent microglia in the pathological processes of AD. Then we propose that targeting senescent microglia holds great promise for therapeutic interventions in neurodegenerative diseases.

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引用次数: 0

Exploring the therapeutic potential of α-(Phenylselanyl) acetophenone in tumor necrosis Factor-α-Induced depressive-like and hyperalgesic behavior in mice

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-28 DOI: 10.1016/j.brainres.2025.149473

Fernanda Severo Sabedra Sousa , Rodolfo Baldinotti , Mariana G. Fronza , Renata Balaguez , Diego Alves , César Augusto Brüning , Lucielli Savegnago

Chronic pain and depression exhibit a high comorbidity, are challenging to manage, and their pathophysiology mechanisms are intricated and closely related to the up-regulation of pro-inflammatory response and oxidative stress. Chronic pain and depression often coexist and present significant management challenges. Their underlying pathophysiological mechanisms are complex and closely linked to the up-regulation of pro-inflammatory responses and oxidative stress. α-(Phenylselanyl) acetophenone (PSAP), an organoselenium compound, has shown antioxidant, antidepressant-like and antinociceptive effects in animal models. This study aimed to evaluate the effects of acute PSAP administration in a comorbid pain-depression model induced by intracerebroventricular (i.c.v.) injection of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) in male Swiss mice. TNF-α (0.1 ƒg/5 µL, i.c.v.) was injected 1 h before the behavioral tests, followed by acute PSAP treatment (10 mg/kg, intragastrically [i.g.]) 30 min post-TNF-α injection. TNF-α decreased the latency time to first immobility episode and increased the total immobility time of mice in the forced swimming test (FST), effects prevented by PSAP treatment. PSAP also reversed TNF-α–induced nociceptive responses in mice, assessed by the hot plate test. These behavioral improvements may be attributed, at least in part, to the capacity of PSAP treatment reverse the TNF-α-induced increase on reactive species and lipoperoxidation levels, as well as modulate altered activities of antioxidant enzymes catalase and superoxide dismutase in the cerebral cortex and hippocampus. Furthermore, PSAP decreased circulating corticosterone levels elevated by TNF-α injection. In conclusion, PSAP emerges as a promising candidate for the development of innovative therapeutic strategies to address the comorbidity of pain and depression.

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引用次数: 0

Paeoniflorin inhibits pyruvate dehydrogenase kinase 3 and promotes BDNF activity by modulating neuronal activity and TNF-α

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-28 DOI: 10.1016/j.brainres.2025.149476

Pinky, Saleha Anwar, Neha, Suhel Parvez

Metabolic dysregulation causes diseases like diabetes and cancer, making PDKs attractive targets. However, a thorough investigation into the unique roles played by the different members of the PDK family, especially PDK3, about memory loss and related diseases like Alzheimer’s disease (AD) is still lacking. The current study investigates PF’s potential to reduce PDK3-associated toxicity in neurodegenerative illnesses, including AD. The association between PF and PDK3 presents a significant opportunity for medication development and AD therapy approaches. PF efficiently suppresses PDK3 activity, as demonstrated by molecular docking and biophysical characterization, providing an in-depth understanding of their molecular interactions. PF significantly inhibited PDK3 in a concentration-dependent manner with an IC50 value of 4.88 µM. Considering this, the current investigation also explores the biological component of PF, which exhibits potential in treating AD and is primarily associated with neuroprotection. In the present study, a 3-hour pre-treatment of PF was administered at varying concentrations (4, 6, and 8 µM) in response to the 24-hour SCP (2 mM)-mediated toxicity. Based on the results of in silico and biophysical characterization, it is concluded that PF inhibits the PDK3 activity. Additionally, it can enhance cell viability, suppress ROS expression, impede apoptosis, and downregulate TNF-α expression. When combined, these actions help to prevent neuronal death in an in vitro model of SCP. PF strengthens the memory marker, which is confirmed through BDNF expression. This study found that all results were more effective at lower and moderate doses of PF. Our research indicates that PF boosts memory, decelerates the progression of oxidative stress, and could potentially serve as a dose-dependent treatment for AD.

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引用次数: 0

A linking hypothesis for eyetracking and mousetracking in the visual world paradigm

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-28 DOI: 10.1016/j.brainres.2025.149477

Michael J. Spivey

For a linking hypothesis in the visual world paradigm to clearly accommodate existing findings and make unambiguous predictions, it needs to be computationally implemented in a fashion that transparently draws the causal connection between the activations of internal representations and the measured output of saccades and reaching movements. Quantitatively implemented linking hypotheses provide an opportunity to not only demonstrate an existence proof of that causal connection but also to test the fidelity of the measuring methods themselves. When a system of interest is measured one way (e.g., ballistic dichotomous outputs) or another way (e.g., smooth graded outputs), the apparent results can differ substantially. What is needed is one linking hypothesis that can produce both types of outputs. The localist attractor network simulation of spoken word recognition demonstrated here recreates eye and mouse movements that capture key findings in the visual world paradigm, and especially relies on one particularly powerful theoretical construct: feedback from the action-perception cycle. Visual feedback from the eye position enhancing the cognitive prominence of the fixated object allows the simulation to fit a wider range of findings, and points to predictions for new experiments. When that feedback is absent, the linking hypothesis simulation no longer fits human data as well. Future experiments, and improvements of this network simulation, are discussed.

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引用次数: 0

Unraveling the dual role of bilirubin in neurological Diseases: A Comprehensive exploration of its neuroprotective and neurotoxic effects

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-27 DOI: 10.1016/j.brainres.2025.149472

Arshdeep Kaur , Rohit , Khadga Raj Aran

Neurodegenerative disorders are characterized by a progressive loss of neurons, causing substantial deficits in motor and cognitive functioning. Bilirubin is a yellow by-product of heme, existing in two primary isoforms namely unconjugated and conjugated, while initially produced unconjugated isomer is lipophilic and cytotoxic in nature. At physiological levels, bilirubin has an important role in brain function by acting as a powerful antioxidant, preventing brain tissues from oxidative damage by eliminating reactive oxygen species (ROS). Additionally, it contributes to immune regulation through microglial activation, cytokine release, complement system interception, fragment crystallization (Fc) receptor modulation, and major histocompatibility complex (MHC II) expression modification, which lower the risk of inflammatory and autoimmune reactions in the central nervous system (CNS). As per the literature, serum bilirubin concentrations are associated with CNS diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), ischemic stroke, hemorrhagic stroke, traumatic brain injury (TBI), multiple sclerosis (MS), epilepsy, schizophrenia and kernicterus spectrum disorder (KSD), which causes neuronal damage, especially in regions like the basal ganglia and cerebellum, which causes movement abnormalities and cognitive deficits. The aim of this article is to explore the dual role of bilirubin as neuroprotective and neurotoxic, essential for establishing effective therapeutic outcomes for neurodegenerative diseases by looking at its cellular mechanisms and discussing how bilirubin’s antioxidant properties can shield neurons and, in some situations, may induce oxidative stress and apoptosis.

{"title":"Unraveling the dual role of bilirubin in neurological Diseases: A Comprehensive exploration of its neuroprotective and neurotoxic effects","authors":"Arshdeep Kaur , Rohit , Khadga Raj Aran","doi":"10.1016/j.brainres.2025.149472","DOIUrl":"10.1016/j.brainres.2025.149472","url":null,"abstract":"<div><div>Neurodegenerative disorders are characterized by a progressive loss of neurons, causing substantial deficits in motor and cognitive functioning. Bilirubin is a yellow by-product of heme, existing in two primary isoforms namely unconjugated and conjugated, while initially produced unconjugated isomer is lipophilic and cytotoxic in nature. At physiological levels, bilirubin has an important role in brain function by acting as a powerful antioxidant, preventing brain tissues from oxidative damage by eliminating reactive oxygen species (ROS). Additionally, it contributes to immune regulation through microglial activation, cytokine release, complement system interception, fragment crystallization (Fc) receptor modulation, and major histocompatibility complex (MHC II) expression modification, which lower the risk of inflammatory and autoimmune reactions in the central nervous system (CNS). As per the literature, serum bilirubin concentrations are associated with CNS diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), ischemic stroke, hemorrhagic stroke, traumatic brain injury (TBI), multiple sclerosis (MS), epilepsy, schizophrenia and kernicterus spectrum disorder (KSD), which causes neuronal damage, especially in regions like the basal ganglia and cerebellum, which causes movement abnormalities and cognitive deficits. The aim of this article is to explore the dual role of bilirubin as neuroprotective and neurotoxic, essential for establishing effective therapeutic outcomes for neurodegenerative diseases by looking at its cellular mechanisms and discussing how bilirubin’s antioxidant properties can shield neurons and, in some situations, may induce oxidative stress and apoptosis.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1851 ","pages":"Article 149472"},"PeriodicalIF":2.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chronic stress-induced neuroplasticity in the prefrontal cortex: Structural, functional, and molecular mechanisms from development to aging

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-27 DOI: 10.1016/j.brainres.2025.149461

Sami Awda Algaidi

Chronic stress profoundly affects the structure and function of the prefrontal cortex (PFC), a brain region critical for executive functions and emotional regulation. This review synthesizes current knowledge on stress-induced PFC plasticity, encompassing structural, functional, and molecular changes. We examine how chronic stress leads to dendritic atrophy, spine loss, and alterations in neuronal connectivity within the PFC, particularly affecting the medial PFC. These structural changes are accompanied by disruptions in neurotransmitter systems, most notably glutamatergic and GABAergic signaling, and alterations in synaptic plasticity mechanisms. At the molecular level, we discuss the intricate interplay between stress hormones, neurotrophic factors, and epigenetic modifications that underlie these changes. The review highlights the significant behavioral and cognitive consequences of stress-induced PFC plasticity, including impairments in working memory, decision-making, and emotional regulation, which may contribute to the development of stress-related psychiatric disorders. We also explore individual differences in stress susceptibility, focusing on sex-specific effects and age-dependent variations in stress responses. The role of estrogens in conferring stress resilience in females and the unique vulnerabilities of the developing and aging PFC are discussed. Finally, we consider potential pharmacological and non-pharmacological interventions that may mitigate or reverse stress-induced changes in the PFC. The review concludes by identifying key areas for future research, including the need for more studies on the reversibility of stress effects and the potential of emerging technologies in unraveling the complexities of PFC plasticity. This comprehensive overview underscores the critical importance of understanding stress-induced PFC plasticity for developing more effective strategies to prevent and treat stress-related mental health disorders.

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引用次数: 0

Elevated plasma Tau-PT217 linked to decreased hippocampal functional connectivity in patients with knee osteoarthritis

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-26 DOI: 10.1016/j.brainres.2025.149478

Ya Wen , Mattia Cannistra , Valeria Sacca , Linting Ma , Liang Feng , Zhongcong Xie , Jian Kong

Background

Osteoarthritis is associated with a higher risk of developing dementia, though the underlying biological mechanisms have remained unclear. Recent studies suggest that blood phosphorylated tau proteins, particularly Tau-PT217, are sensitive biomarkers capable of detecting cognitive decline in its early stages, making it useful for early diagnosis of Alzheimer’s disease and other forms of cognitive impairment.

Methods

In this study, we investigated the plasma phosphorylated tau protein levels (Tau-PT217 and Tau-PT181), hippocampus functional connectivity, and cognitive function in people with knee osteoarthritis compared to age and gender matched pain-free controls.

Results

We found that knee osteoarthritis was associated with increased plasma levels of Tau-PT217 (but not Tau-PT181), and that the Tau-PT217 is also correlated with reduced hippocampal functional connectivity with middle cingulate cortex. Our findings suggest a potential biological correlation between knee osteoarthritis and an elevated risk of dementia, contributing valuable insights that may guide the formulation of early intervention and preventative strategies to mitigate dementia in individuals with knee osteoarthritis.

{"title":"Elevated plasma Tau-PT217 linked to decreased hippocampal functional connectivity in patients with knee osteoarthritis","authors":"Ya Wen , Mattia Cannistra , Valeria Sacca , Linting Ma , Liang Feng , Zhongcong Xie , Jian Kong","doi":"10.1016/j.brainres.2025.149478","DOIUrl":"10.1016/j.brainres.2025.149478","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis is associated with a higher risk of developing dementia, though the underlying biological mechanisms have remained unclear. Recent studies suggest that blood phosphorylated tau proteins, particularly Tau-PT217, are sensitive biomarkers capable of detecting cognitive decline in its early stages, making it useful for early diagnosis of Alzheimer’s disease and other forms of cognitive impairment.</div></div><div><h3>Methods</h3><div>In this study, we investigated the plasma phosphorylated tau protein levels (Tau-PT217 and Tau-PT181), hippocampus functional connectivity, and cognitive function in people with knee osteoarthritis compared to age and gender matched pain-free controls.</div></div><div><h3>Results</h3><div>We found that knee osteoarthritis was associated with increased plasma levels of Tau-PT217 (but not Tau-PT181), and that the Tau-PT217 is also correlated with reduced hippocampal functional connectivity with middle cingulate cortex. Our findings suggest a potential biological correlation between knee osteoarthritis and an elevated risk of dementia, contributing valuable insights that may guide the formulation of early intervention and preventative strategies to mitigate dementia in individuals with knee osteoarthritis.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1851 ","pages":"Article 149478"},"PeriodicalIF":2.7,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

rTMS improves cognitive function and its real-time and cumulative effect on neuronal excitability in aged mice

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research

Pub Date : 2025-01-25 DOI: 10.1016/j.brainres.2025.149474

Chong Ding , Xueting Pan , Rui Fu , Haoyu Qiu , Haijun Zhu

Repetitive transcranial magnetic stimulation (rTMS) is acknowledged for its critical role in modulating neuronal excitability and enhancing cognitive function. The dentate gyrus of the hippocampus is closely linked to cognitive processes; however, the precise mechanisms by which changes in its excitability influence cognition are not yet fully understood. This study aimed to elucidate the effects on granule cell excitability and the effects on cognition of high-frequency rTMS in naturally aging mice, as well as to investigate the potential interactions between these two factors. It was observed that 20 Hz high-frequency rTMS attenuated granule cell loss in aged mice, demonstrating both cumulative and real-time effects on neural excitability. Importantly, this intervention significantly ameliorated age-related cognitive decline. The findings suggest that one of the potential mechanisms underlying the amelioration of age-related cognitive decline through high-frequency rTMS may involve the attenuation of granule cell apoptosis and the enhancement of their neural excitability.

{"title":"rTMS improves cognitive function and its real-time and cumulative effect on neuronal excitability in aged mice","authors":"Chong Ding , Xueting Pan , Rui Fu , Haoyu Qiu , Haijun Zhu","doi":"10.1016/j.brainres.2025.149474","DOIUrl":"10.1016/j.brainres.2025.149474","url":null,"abstract":"<div><div>Repetitive transcranial magnetic stimulation (rTMS) is acknowledged for its critical role in modulating neuronal excitability and enhancing cognitive function. The dentate gyrus of the hippocampus is closely linked to cognitive processes; however, the precise mechanisms by which changes in its excitability influence cognition are not yet fully understood. This study aimed to elucidate the effects on granule cell excitability and the effects on cognition of high-frequency rTMS in naturally aging mice, as well as to investigate the potential interactions between these two factors. It was observed that 20 Hz high-frequency rTMS attenuated granule cell loss in aged mice, demonstrating both cumulative and real-time effects on neural excitability. Importantly, this intervention significantly ameliorated age-related cognitive decline. The findings suggest that one of the potential mechanisms underlying the amelioration of age-related cognitive decline through high-frequency rTMS may involve the attenuation of granule cell apoptosis and the enhancement of their neural excitability.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1851 ","pages":"Article 149474"},"PeriodicalIF":2.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0