Brain Research Bulletin最新文献_第4页

Addressing myelination disorders: Novel strategies using human 3D peripheral nerve model

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-02-10 DOI: 10.1016/j.brainresbull.2025.111252

Camille Loret , Camille Scherrer , Amandine Rovini , Esther Lesage , Laurence Richard , Aurore Danigo , Franck Sturtz , Frédéric Favreau , Pierre-Antoine Faye , Anne-Sophie Lia

Peripheral myelination disorders encompass a variety of disorders that affect myelin sheaths in the peripheral nervous system. The Charcot-Marie-Tooth disease (CMT), the most common inherited peripheral neuropathy, is one of the most prevalent among them. CMT stems from a wide range of genetic causes that disrupt the nerve conduction, leading to progressive muscle weakness and atrophy, sensory loss, and motor function impairment. Historically, the study of these disorders has relied heavily on animal studies, owing to the challenges in accessing human cells. However, the advent of human induced pluripotent stem cell (hiPSC)-derived neuronal cells has addressed these limitations in the realm of peripheral myelination disorders. Despite this, obtaining myelin in these models remains an expensive, time-consuming, and material-intensive process. This study presents a novel, cost-effective method utilizing hiPSC-derived Schwann cells and motor neurons in a three-dimensional culture system. Our method successfully enabled the acquisition of myelin in a control clone within just four weeks, as confirmed by electron microscopy. Furthermore, the utility of these approaches was validated by studying CMT4C, also named AR-CMTde-SH3TC2, the most common recessive demyelinating form of CMT. This revealed defects in Schwann cell support to motor neuron neurite outgrowth and impaired myelination in disease-specific hiPSC-derived lines. This approach offers valuable insights into the pathogenesis of peripheral myelination disorders and provides a platform for testing potential therapeutic strategies.

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引用次数: 0

Gut microbiome composition changes in obstructive sleep apnoea syndrome also in relation to excessive daytime sleepiness

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-02-10 DOI: 10.1016/j.brainresbull.2025.111251

Mariana Fernandes , Orazio Palmieri , Stefano Castellana , Matteo Spanetta , Tiziana Latiano , Clementina Lupo , Claudia De Masi , Christian Cardile , Carmen Calvello , Francesca Izzi , Fabio Placidi , Tommaso Mazza , Nicola Biagio Mercuri , Anna Latiano , Claudio Liguori

Introduction

Obstructive sleep apnoea syndrome (OSAS) is considered a risk factor for several comorbidities. Alteration in gut microbiome was documented in OSAS animal models and in paediatric patients. This study analysed gut microbiome composition in adult patients with OSAS compared to healthy controls. Further, the effect of excessive daytime sleepiness (EDS) on gut microbiome was evaluated.

Methods

Adult patients with OSAS underwent polysomnographic recording and completed the Epworth Sleepiness Scale (ESS) to assess EDS. Faecal samples were collected and compared between patients and healthy controls. Composition, community diversity, differences in taxa abundance profiles and sample dysbiosis were evaluated through 16S metagenomics and multiple bioinformatics algorithms. OSAS patients were distributed in two groups according to EDS (ESS score≥10) to assess differences in clinical, polysomnographic and faecal data.

Results

Twenty-three OSAS patients were compared to 44 healthy controls. Patients presented significant differences of gut microbiome biodiversity, specifically in qualitative alpha diversity metrics (Faith’s PD Kruskal-Wallis test, p-value=0.003; Number_of_Observed_Features, p-value =0.001). OSAS patients tend to cluster together, at least for Jaccard and Unweighted UniFrac distance-based PERMANOVA tests (q-values=0.02 and =0.003, respectively). Several taxa were detected as different in abundance between OSAS patients and healthy controls, although, globally, OSAS patients cannot be considered as “dysbiotic”. Differences in bacteria composition were evident between OSAS patients with and those without EDS.

Conclusions

OSAS is associated with gut microbiome alteration in adult patients. EDS in OSAS seems to characterize a different gut microbiome composition, although it can be only hypothesized a gut-mediated effect on EDS in OSAS.

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引用次数: 0

The antioxidant role of aromatic plant extracts in managing neurodegenerative diseases: A comprehensive review

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-02-10 DOI: 10.1016/j.brainresbull.2025.111253

Youyang Zhu , Miao Tian , Shiyu Lu , Yuliang Qin , Ting Zhao , Hongling Shi , Zhaofu Li , Dongdong Qin

Neurodegenerative diseases (NDDs) are a class of cognitive and motor disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), and others. They are caused by lesions in cells and tissues of the central nervous system, resulting in corresponding dysfunctions and consequent decline in cognitive and motor functions. Neural tissues are extremely vulnerable to oxidative stress, which plays critical biological roles in NDDs. Aromatic compounds are found extensively in natural plants and have substantial effects of anti-oxidative stress damage, which not only have a wide range of research applications in cosmetics, foods, etc., but are also frequently utilized in the treatment of various central nervous system diseases. This review summarizes the relevant oxidative stress mechanisms in NDDs (AD, PD, HD, and ALS) and reviews aromatic compounds such as polyphenols, terpenoids, and flavonoids that can be used in the management of neurodegenerative diseases, as well as their specific mechanisms of antioxidant action. This review will serve as a reference for future experimental studies on neurodegenerative illnesses while also offering fresh insights into clinical therapy.

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引用次数: 0

Peripheral mitochondrial transplantation alleviates diabetes-associated cognitive dysfunction by suppressing cuproptosis

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-02-07 DOI: 10.1016/j.brainresbull.2025.111245

Juan Hu , Qiao Li , Shiqiu Jiang , Yingying Deng , Lan Yang , Mengyu Du , Shuxuan He , Fuxing Xu , Chaoying Yan , Wei Gao , Yansong Li , Yaomin Zhu

Mitochondrial dysfunction and neuronal impairment are hallmark features of Diabetes-Associated Cognitive Dysfunction (DACD), mitochondrial transplantation is also a therapeutic intervention for DACD. However, the precise mechanism underlying its therapeutic effects are not fully elucidated. Given that imbalances in copper homeostasis and cuproptosis are associated with various neurodegenerative disorders and diabetic myocardial damage, we hypothesize a role for cuproptosis in the pathogenesis of DACD. We further propose that therapeutic peripheral mitochondrial transplantation may ameliorate DACD by reducing processes of cuproptosis. In this research, the study delved into the expression levels of cuproptosis-associated proteins FDX1, LIAS, and DLAT, as well as the copper content in both type 2 diabetes mellitus (T2DM) mice and primary neuronal cells exposed to high glucose and palmitic acid (HG/Pal). Furthermore, the cognitive capabilities of the mice were evaluated using a series of behavioral tests. The findings revealed that in primary neurons exposed to HG/Pal, the expression of copper levels was elevated, and the levels of FDX1, LIAS, and DLAT were reduced. Post-transplantation of platelet-derived mitochondria (Mito-Plt), a significant reversal of these biomarkers was noted, coincident with an improvement in cognitive deficits in T2DM mice. Significantly, the cuproptosis agonist elesclomol (ES) aggravated these alterations. In summary, the findings collectively suggest a causal connection between DACD and the development of cuproptosis in neurons. The use of exogenous Mito-Plt presents a promising therapeutic approach, capable of rescuing neurons from cuproptosis and thereby potentially alleviating DACD.

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引用次数: 0

Unraveling the PVTGlu-mPFCGlu circuit: A new frontier in chronic pain management for bone cancer pain

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-02-06 DOI: 10.1016/j.brainresbull.2025.111235

Liqun Duan , Qianliang Wang , Jianpeng Chen , Zelin Fan , Wenzhi Zhang , Jun Yan

Bone cancer pain (BCP) is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone metastasis. BCP impairs patients’ quality of life. Depending upon clinical observations, the administration of centrally acting analgesic has been associated with the alleviation of pain symptoms BCP patients. Central nervous system sensitization performs a crucial role in pain-regulating perception in BCP. Nevertheless, the precise neural circuitry and mechanism of action remain enigmatic. In the present study, we observed the activation of glutamatergic neurons in the Prelimbic cortex (mPFC) and paraventricular thalamus (PVT) in BCP mice. Experimental validation using viral tracers confirmed the existence of a projection pathway between the PVT and mPFC. Inhibition of the input from PVT glutamatergic neurons to mPFC glutamatergic neurons alleviates chronic pain in BCP, whereas activation of the PVT^Glu-mPFC^Glu projection induces chronic pain in mice. These findings imply a pivotal role for the PVT^Glu-mPFC^Glu circuit in the regulation of chronic pain in BCP.

{"title":"Unraveling the PVTGlu-mPFCGlu circuit: A new frontier in chronic pain management for bone cancer pain","authors":"Liqun Duan , Qianliang Wang , Jianpeng Chen , Zelin Fan , Wenzhi Zhang , Jun Yan","doi":"10.1016/j.brainresbull.2025.111235","DOIUrl":"10.1016/j.brainresbull.2025.111235","url":null,"abstract":"<div><div><strong>Bone cancer pain (BCP)</strong> is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone metastasis. BCP impairs patients’ quality of life. Depending upon clinical observations, the administration of centrally acting analgesic has been associated with the alleviation of pain symptoms BCP patients. Central nervous system sensitization performs a crucial role in pain-regulating perception in BCP. Nevertheless, the precise neural circuitry and mechanism of action remain enigmatic. In the present study, we observed the activation of glutamatergic neurons in the Prelimbic cortex (mPFC) and paraventricular thalamus (PVT) in BCP mice. Experimental validation using viral tracers confirmed the existence of a projection pathway between the PVT and mPFC. Inhibition of the input from PVT glutamatergic neurons to mPFC glutamatergic neurons alleviates chronic pain in BCP, whereas activation of the PVT<sup>Glu</sup>-mPFC<sup>Glu</sup> projection induces chronic pain in mice. These findings imply a pivotal role for the PVT<sup>Glu</sup>-mPFC<sup>Glu</sup> circuit in the regulation of chronic pain in BCP.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111235"},"PeriodicalIF":3.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MicroRNA-155 modulates methotrexate-induced spatial memory impairment by disruption of the blood-brain barrier integrity

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-02-06 DOI: 10.1016/j.brainresbull.2025.111240

Yu-Chieh Chen , Li-Tung Huang , Hong-Ren Yu , Jiunn-Ming Sheen

Aim

Methotrexate (MTX) is a commonly used chemotherapy drug, yet its late neurotoxic side effects are gaining attention. The aim of the study was to evaluate the role of miR-155 in the pathogenesis of MTX-induced cognitive impairment, mainly focused on the interplay of blood-brain barrier (BBB) integrity and MTX toxicity.

Main methods

We use young rat model mimicking children leukemia treatment protocol, focusing on the systemic MTX effect on the central nervous system by intraperitoneal (IP) MTX injection. The cognitive function was evaluated by Morris Water Maze test and the BBB integrity was accessed by cortex permeability test. Tight junction proteins expression were also examined. Finally, we tested whether anti-miR155 pretreatment can reversed the MTX effect.

Key findings

We found increased plasma miR-155 expression at 24 hr after IP MTX treatment. Besides, IP MTX resulted in impaired learning acquisition, which can be reversed by anti-miR155 treatment. Furthermore, brain cortex permeability and tight junction proteins were changed by IP MTX. miR-155 revealed its protective role in the current study for the development of MTX-induced cognitive impairment.

Significance

IP MTX can induce significant cognitive impairment, which is related to the disruption of BBB integrity. miR-155 plays a vital role in the regulation of MTX-induced cognitive impairment, mainly through the maintenance of BBB integrity.

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引用次数: 0

The mirror preference test: A reverse translational approach to study anomalous subjective experience in rats

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-02-05 DOI: 10.1016/j.brainresbull.2025.111247

Daria Chestnykh , Liubov S. Kalinichenko , Stephan von Hörsten , Johannes Kornhuber , Christian P. Müller

Significant advancements have been made in the treatment of psychotic disorders, yet current pharmacotherapy remains inadequate. Symptoms related to the misinterpretation of reality are crucial for diagnosis but pose challenges for preclinical research. In humans, a Mirror-Gazing test is used to examine abnormal self-experience and to predict the risk of schizophrenia. To address this, we developed a task to evaluate anomalous subjective experiences in rats using a Mirror-Preference test. Here we demonstrate that naive rats show a preference for a mirror chamber, which was followed by significant habituation over a series of trials. In subsequent tests, we utilized dimmed lighting and net-covered mirrors to induce incomplete mirror images. Acute stimulation with amphetamine (AMPH, 3 mg/kg, i.p.) further increased the preference for the mirror. In a model of psychosis induced by chronic AMPH administration, rats showed fewer and shorter interactions with the mirror but maintained their preference for the chamber where psychotic-like animals were given additional AMPH stimulation (1.5 mg/kg, i.p.) before testing. Here, a surprising reversal in chamber preference was observed, along with decreased frequency and duration of mirror contact, suggesting mirror avoidance. The AMPH-presensitized rats also exhibited hyperlocomotion and elevated anxiety, indicative of psychotic-like behaviour. Although self-recognition in rodents is debatable, recent studies suggest they can discriminate mirror images. We propose that limited visual perception that meets brain monoamine sensitization may trigger visual illusions as part of a psychotic-like state in rats. This novel approach can be utilized to test intervention strategies for psychosis in rats.

{"title":"The mirror preference test: A reverse translational approach to study anomalous subjective experience in rats","authors":"Daria Chestnykh , Liubov S. Kalinichenko , Stephan von Hörsten , Johannes Kornhuber , Christian P. Müller","doi":"10.1016/j.brainresbull.2025.111247","DOIUrl":"10.1016/j.brainresbull.2025.111247","url":null,"abstract":"<div><div>Significant advancements have been made in the treatment of psychotic disorders, yet current pharmacotherapy remains inadequate. Symptoms related to the misinterpretation of reality are crucial for diagnosis but pose challenges for preclinical research. In humans, a Mirror-Gazing test is used to examine abnormal self-experience and to predict the risk of schizophrenia. To address this, we developed a task to evaluate anomalous subjective experiences in rats using a Mirror-Preference test. Here we demonstrate that naive rats show a preference for a mirror chamber, which was followed by significant habituation over a series of trials. In subsequent tests, we utilized dimmed lighting and net-covered mirrors to induce incomplete mirror images. Acute stimulation with amphetamine (AMPH, 3 mg/kg, i.p.) further increased the preference for the mirror. In a model of psychosis induced by chronic AMPH administration, rats showed fewer and shorter interactions with the mirror but maintained their preference for the chamber where psychotic-like animals were given additional AMPH stimulation (1.5 mg/kg, i.p.) before testing. Here, a surprising reversal in chamber preference was observed, along with decreased frequency and duration of mirror contact, suggesting mirror avoidance. The AMPH-presensitized rats also exhibited hyperlocomotion and elevated anxiety, indicative of psychotic-like behaviour. Although self-recognition in rodents is debatable, recent studies suggest they can discriminate mirror images. We propose that limited visual perception that meets brain monoamine sensitization may trigger visual illusions as part of a psychotic-like state in rats. This novel approach can be utilized to test intervention strategies for psychosis in rats.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111247"},"PeriodicalIF":3.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143196043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Individualized prediction of multi-domain intelligence quotient in bipolar disorder patients using resting-state functional connectivity

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-02-03 DOI: 10.1016/j.brainresbull.2025.111238

Xiaoyu Li , Wei Wei , Linze Qian , Xiaojing Li , Mingli Li , Ioannis Kakkos , Qiang Wang , Hua Yu , Wanjun Guo , Xiaohong Ma , George K. Matsopoulos , Liansheng Zhao , Wei Deng , Yu Sun , Tao Li

Background

Although accumulating studies have explored the neural underpinnings of intelligence quotient (IQ) in patients with bipolar disorder (BD), these studies utilized a classification/comparison scheme that emphasized differences between BD and healthy controls at a group level. The present study aimed to infer BD patients’ IQ scores at the individual level using a prediction model.

Methods

We applied a cross-validated Connectome-based Predictive Modeling (CPM) framework using resting-state fMRI functional connectivity (FCs) to predict BD patients’ IQ scores, including verbal IQ (VIQ), performance IQ (PIQ), and full-scale IQ (FSIQ). For each IQ domain, we selected the FCs that contributed to the predictions and described their distribution across eight widely-recognized functional networks. Moreover, we further explored the overlapping patterns of the contributed FCs for different IQ domains.

Results

The CPM achieved statistically significant prediction performance for three IQ domains in BD patients. Regarding the contributed FCs, we observed a widespread distribution of internetwork FCs across somatomotor, visual, dorsal attention, and ventral attention networks, demonstrating their correspondence with aberrant FCs correlated to cognition deficits in BD patients. A convergent pattern in terms of contributed FCs for different IQ domains was observed, as evidenced by the shared-FCs with a leftward hemispheric dominance.

Conclusions

The present study preliminarily explored the feasibility of inferring individual IQ scores in BD patients using the FCs-based CPM framework. It is a step toward the development of applicable techniques for quantitative and objective cognitive assessment in BD patients and contributes novel insights into understanding the complex neural mechanisms underlying different IQ domains.

{"title":"Individualized prediction of multi-domain intelligence quotient in bipolar disorder patients using resting-state functional connectivity","authors":"Xiaoyu Li , Wei Wei , Linze Qian , Xiaojing Li , Mingli Li , Ioannis Kakkos , Qiang Wang , Hua Yu , Wanjun Guo , Xiaohong Ma , George K. Matsopoulos , Liansheng Zhao , Wei Deng , Yu Sun , Tao Li","doi":"10.1016/j.brainresbull.2025.111238","DOIUrl":"10.1016/j.brainresbull.2025.111238","url":null,"abstract":"<div><h3>Background</h3><div>Although accumulating studies have explored the neural underpinnings of intelligence quotient (IQ) in patients with bipolar disorder (BD), these studies utilized a classification/comparison scheme that emphasized differences between BD and healthy controls at a group level. The present study aimed to infer BD patients’ IQ scores at the individual level using a prediction model.</div></div><div><h3>Methods</h3><div>We applied a cross-validated Connectome-based Predictive Modeling (CPM) framework using resting-state fMRI functional connectivity (FCs) to predict BD patients’ IQ scores, including verbal IQ (VIQ), performance IQ (PIQ), and full-scale IQ (FSIQ). For each IQ domain, we selected the FCs that contributed to the predictions and described their distribution across eight widely-recognized functional networks. Moreover, we further explored the overlapping patterns of the contributed FCs for different IQ domains.</div></div><div><h3>Results</h3><div>The CPM achieved statistically significant prediction performance for three IQ domains in BD patients. Regarding the contributed FCs, we observed a widespread distribution of internetwork FCs across somatomotor, visual, dorsal attention, and ventral attention networks, demonstrating their correspondence with aberrant FCs correlated to cognition deficits in BD patients. A convergent pattern in terms of contributed FCs for different IQ domains was observed, as evidenced by the shared-FCs with a leftward hemispheric dominance.</div></div><div><h3>Conclusions</h3><div>The present study preliminarily explored the feasibility of inferring individual IQ scores in BD patients using the FCs-based CPM framework. It is a step toward the development of applicable techniques for quantitative and objective cognitive assessment in BD patients and contributes novel insights into understanding the complex neural mechanisms underlying different IQ domains.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111238"},"PeriodicalIF":3.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association of cortical macrostructural and microstructural changes with cognitive performance and gene expression in subcortical ischemic vascular disease patients with cognitive impairment

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-02-03 DOI: 10.1016/j.brainresbull.2025.111239

Jing Huang , Runtian Cheng , Xiaoshuang Liu , Li Chen , Tianyou Luo

Objective

Previous researches have demonstrated that patients with subcortical ischemic vascular disease (SIVD) exhibited brain structure abnormalities. However, the cortical macrostructural and microstructural characteristics and their relationship with cognitive scores and gene expression in SIVD patients remain largely unknown.

Methods

This study collected 3D-T1 and diffusion tensor imaging data from 30 SIVD patients with cognitive impairment (SIVD-CI) and 32 normal controls. The between-group comparative analyses of cortical thickness, area, volume, local gyrification index (LGI), and mean diffusivity (MD) were conducted with a general linear model. Moreover, the associations between the significant neuroimaging values and the cognitive scores and gene expression values from Allen Human Brain Atlas database were evaluated using partial least squares regression and partial correlation analysis.

Results

SIVD-CI patients showed significant decreases in cortical thicknesses across 18 regions, cortical volumes across three regions, and cortical LGI across five regions, as well as significant increases in cortical MD across five regions (P < 0.05). The significantly reduced cortical thicknesses of the right insula, left superior temporal gyrus, left central anterior gyrus, and left caudal anterior cingulate cortex, as well as the significantly reduced cortical LGI in left caudal anterior cingulate cortex, were significantly positively correlated with different cognitive scores (P < 0.05). Furthermore, the abnormal cortical structural indicators were found to be significantly related to nine risk genes (VCAN, APOE, EFEMP1, SALL1, BCAN, KCNK2, EPN2, DENND1B and XKR6) (P < 0.05).

Conclusions

The specific cortical structural damage may be related to specific cognitive decline and specific risk genes in SIVD-CI patients.

{"title":"Association of cortical macrostructural and microstructural changes with cognitive performance and gene expression in subcortical ischemic vascular disease patients with cognitive impairment","authors":"Jing Huang , Runtian Cheng , Xiaoshuang Liu , Li Chen , Tianyou Luo","doi":"10.1016/j.brainresbull.2025.111239","DOIUrl":"10.1016/j.brainresbull.2025.111239","url":null,"abstract":"<div><h3>Objective</h3><div>Previous researches have demonstrated that patients with subcortical ischemic vascular disease (SIVD) exhibited brain structure abnormalities. However, the cortical macrostructural and microstructural characteristics and their relationship with cognitive scores and gene expression in SIVD patients remain largely unknown.</div></div><div><h3>Methods</h3><div>This study collected 3D-T1 and diffusion tensor imaging data from 30 SIVD patients with cognitive impairment (SIVD-CI) and 32 normal controls. The between-group comparative analyses of cortical thickness, area, volume, local gyrification index (LGI), and mean diffusivity (MD) were conducted with a general linear model. Moreover, the associations between the significant neuroimaging values and the cognitive scores and gene expression values from Allen Human Brain Atlas database were evaluated using partial least squares regression and partial correlation analysis.</div></div><div><h3>Results</h3><div>SIVD-CI patients showed significant decreases in cortical thicknesses across 18 regions, cortical volumes across three regions, and cortical LGI across five regions, as well as significant increases in cortical MD across five regions (<em>P</em> < 0.05). The significantly reduced cortical thicknesses of the right insula, left superior temporal gyrus, left central anterior gyrus, and left caudal anterior cingulate cortex, as well as the significantly reduced cortical LGI in left caudal anterior cingulate cortex, were significantly positively correlated with different cognitive scores (<em>P</em> < 0.05). Furthermore, the abnormal cortical structural indicators were found to be significantly related to nine risk genes (VCAN, APOE, EFEMP1, SALL1, BCAN, KCNK2, EPN2, DENND1B and XKR6) (<em>P</em> < 0.05).</div></div><div><h3>Conclusions</h3><div>The specific cortical structural damage may be related to specific cognitive decline and specific risk genes in SIVD-CI patients.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"222 ","pages":"Article 111239"},"PeriodicalIF":3.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143196634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glucose metabolism impairment in major depressive disorder 重度抑郁症的糖代谢障碍。

IF 3.5 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-02-01 DOI: 10.1016/j.brainresbull.2025.111191

Fanhao Meng , Jing Wang , Long Wang , Wei Zou

Major depressive disorder (MDD) is a common mental disorder with chronic tendencies that seriously affect regular work, life, and study. However, its exact pathogenesis remains unclear. Patients with MDD experience systemic and localized impairments in glucose metabolism throughout the disease course, disrupting various processes such as glucose uptake, glycoprotein transport, glycolysis, the tricarboxylic acid cycle (TCA), and oxidative phosphorylation (OXPHOS). These impairments may result from mechanisms including insulin resistance, hyperglycemia-induced damage, oxidative stress, astrocyte abnormalities, and mitochondrial dysfunction, leading to insufficient energy supply, altered synaptic plasticity, neuronal cell death, and functional and structural damage to reward networks. These mechanical changes contribute to the pathogenesis of MDD and severely interfere with the prognosis. Herein, we summarized the impairment of glucose metabolism and its pathophysiological mechanisms in patients with MDD. In addition, we briefly discussed potential pharmacological interventions for glucose metabolism to alleviate MDD, including glucagon-like peptide-1 receptor agonists, metformin, topical insulin, liraglutide, and pioglitazone, to encourage the development of new therapeutics.

重度抑郁症（MDD）是一种常见的精神障碍，具有慢性倾向，严重影响正常的工作、生活和学习。然而，其确切的发病机制尚不清楚。在整个疾病过程中，MDD患者会经历全身和局部的葡萄糖代谢损伤，破坏葡萄糖摄取、糖蛋白转运、糖酵解、三羧酸循环（TCA）和氧化磷酸化（OXPHOS）等多种过程。这些损伤的机制可能包括胰岛素抵抗、高血糖诱导的损伤、氧化应激、星形胶质细胞异常和线粒体功能障碍，导致能量供应不足、突触可塑性改变、神经元细胞死亡以及奖励网络的功能和结构损伤。这些机械变化有助于MDD的发病机制，并严重影响预后。在此，我们总结了重度抑郁症患者的糖代谢障碍及其病理生理机制。此外，我们简要地讨论了葡萄糖代谢的潜在药物干预措施，包括胰高血糖素样肽-1受体激动剂、二甲双胍、外用胰岛素、利拉鲁肽和吡格列酮，以促进新疗法的发展。

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引用次数: 0