Journal of Neuroscience Research最新文献

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Early-life and chronic exposure to high-fat diet alters noradrenergic and glutamatergic neurotransmission in the male rat amygdala and hippocampus under cognitive challenges 在认知挑战下,雄性大鼠杏仁核和海马的去甲肾上腺素能和谷氨酸能神经传递会发生改变。
IF 4.2 3区 医学
Journal of Neuroscience Research Pub Date : 2024-06-07 DOI: 10.1002/jnr.25360
Daniel Osorio-Gómez, Claudia I. Perez, Pamela Salcedo-Tello, Arturo Hernández-Matias, Susana Hernández-Ramírez, Benjamin Arroyo, Gustavo Pacheco-López, Ranier Gutierrez, Federico Bermúdez-Rattoni, Kioko Guzmán-Ramos, OBETEEN Consortium
{"title":"Early-life and chronic exposure to high-fat diet alters noradrenergic and glutamatergic neurotransmission in the male rat amygdala and hippocampus under cognitive challenges","authors":"Daniel Osorio-Gómez,&nbsp;Claudia I. Perez,&nbsp;Pamela Salcedo-Tello,&nbsp;Arturo Hernández-Matias,&nbsp;Susana Hernández-Ramírez,&nbsp;Benjamin Arroyo,&nbsp;Gustavo Pacheco-López,&nbsp;Ranier Gutierrez,&nbsp;Federico Bermúdez-Rattoni,&nbsp;Kioko Guzmán-Ramos,&nbsp;OBETEEN Consortium","doi":"10.1002/jnr.25360","DOIUrl":"10.1002/jnr.25360","url":null,"abstract":"<p>Childhood obesity increases the risk of health and cognitive disorders in adulthood. Consuming high-fat diets (HFD) during critical neurodevelopmental periods, like childhood, impairs cognition and memory in humans and animals, affecting the function and connectivity of brain structures related to emotional memory. However, the underlying mechanisms of such phenomena need to be better understood. This study aimed to investigate the neurochemical profile of the amygdala and hippocampus, brain structures involved in emotional memory, during the acquisition of conditioned odor aversion in male rats that consumed a HFD from weaning to adulthood. The rats gained weight, experienced metabolic changes, and reduced insulin sensitivity and glucose tolerance. Rats showed enhanced odor aversion memory, contrary to the expected cognitive impairments. This memory enhancement was accompanied by increased noradrenergic and glutamatergic neurotransmission in the amygdala and hippocampus. Importantly, this upregulation was specific to stimuli exposure, as basal neurotransmitter levels remained unaltered by the HFD. Our results suggest that HFD modifies cognitive function by altering neurochemical signaling, in this case, upregulating neurotransmitter levels rendering a stronger memory trace, demonstrating that metabolic dysfunctions do not only trigger exclusively detrimental plasticity processes but also render enhanced plastic effects depending on the type of information.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 6","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25360","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283943","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
GABAergic system and chloride cotransporters as potential therapeutic targets to mitigate cell death in ischemia GABA 能系统和氯化物共转运体是减轻缺血时细胞死亡的潜在治疗靶点。
IF 4.2 3区 医学
Journal of Neuroscience Research Pub Date : 2024-05-29 DOI: 10.1002/jnr.25355
A. A. Nascimento, D. Pereira-Figueiredo, V. P. Borges-Martins, R. C. Kubrusly, K. C. Calaza
{"title":"GABAergic system and chloride cotransporters as potential therapeutic targets to mitigate cell death in ischemia","authors":"A. A. Nascimento,&nbsp;D. Pereira-Figueiredo,&nbsp;V. P. Borges-Martins,&nbsp;R. C. Kubrusly,&nbsp;K. C. Calaza","doi":"10.1002/jnr.25355","DOIUrl":"10.1002/jnr.25355","url":null,"abstract":"<p>Gamma aminobutyric acid (GABA) is a critical inhibitory neurotransmitter in the central nervous system that plays a vital role in modulating neuronal excitability. Dysregulation of GABAergic signaling, particularly involving the cotransporters NKCC1 and KCC2, has been implicated in various pathologies, including epilepsy, schizophrenia, autism spectrum disorder, Down syndrome, and ischemia. NKCC1 facilitates chloride influx, whereas KCC2 mediates chloride efflux via potassium gradient. Altered expression and function of these cotransporters have been associated with excitotoxicity, inflammation, and cellular death in ischemic events characterized by reduced cerebral blood flow, leading to compromised tissue metabolism and subsequent cell death. NKCC1 inhibition has emerged as a potential therapeutic approach to attenuate intracellular chloride accumulation and mitigate neuronal damage during ischemic events. Similarly, targeting KCC2, which regulates chloride efflux, holds promise for improving outcomes and reducing neuronal damage under ischemic conditions. This review emphasizes the critical roles of GABA, NKCC1, and KCC2 in ischemic pathologies and their potential as therapeutic targets. Inhibiting or modulating the activity of these cotransporters represents a promising strategy for reducing neuronal damage, preventing excitotoxicity, and improving neurological outcomes following ischemic events. Furthermore, exploring the interactions between natural compounds and NKCC1/KCC2 provides additional avenues for potential therapeutic interventions for ischemic injury.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
The influence of accelerated brain aging on coactivation pattern dynamics in Parkinson's disease 大脑加速衰老对帕金森病共激活模式动态的影响。
IF 4.2 3区 医学
Journal of Neuroscience Research Pub Date : 2024-05-27 DOI: 10.1002/jnr.25357
Su Yan, Jun Lu, Hongquan Zhu, Tian Tian, Yuanyuan Qin, Yuanhao Li, Wenzhen Zhu
{"title":"The influence of accelerated brain aging on coactivation pattern dynamics in Parkinson's disease","authors":"Su Yan,&nbsp;Jun Lu,&nbsp;Hongquan Zhu,&nbsp;Tian Tian,&nbsp;Yuanyuan Qin,&nbsp;Yuanhao Li,&nbsp;Wenzhen Zhu","doi":"10.1002/jnr.25357","DOIUrl":"10.1002/jnr.25357","url":null,"abstract":"<p>Aging is widely acknowledged as the primary risk factor for brain degeneration, with Parkinson's disease (PD) tending to follow accelerated aging trajectories. We aim to investigate the impact of structural brain aging on the temporal dynamics of a large-scale functional network in PD. We enrolled 62 PD patients and 32 healthy controls (HCs). The level of brain aging was determined by calculating global and local brain age gap estimates (G-brainAGE and L-brainAGE) from structural images. The neural network activity of the whole brain was captured by identifying coactivation patterns (CAPs) from resting-state functional images. Intergroup differences were assessed using the general linear model. Subsequently, a spatial correlation analysis between the L-brainAGE difference map and CAPs was conducted to uncover the anatomical underpinnings of functional alterations. Compared to HCs (−3.73 years), G-brainAGE was significantly higher in PD patients (+1.93 years), who also exhibited widespread elevation in L-brainAGE. G-brainAGE was correlated with disease severity and duration. PD patients spent less time in CAPs involving activated default mode and the fronto-parietal network (DMN-FPN), as well as the sensorimotor and salience network (SMN-SN), and had a reduced transition frequency from other CAPs to the DMN-FPN and SMN-SN CAPs. Furthermore, the pattern of localized brain age acceleration showed spatial similarities with the SMN-SN CAP. Accelerated structural brain aging in PD adversely affects brain function, manifesting as dysregulated brain network dynamics. These findings provide insights into the neuropathological mechanisms underlying neurodegenerative diseases and imply the possibility of interventions for modifying PD progression by slowing the brain aging process.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
The interplay between glucose and ketone bodies in neural stem cell metabolism 葡萄糖和酮体在神经干细胞新陈代谢中的相互作用。
IF 4.2 3区 医学
Journal of Neuroscience Research Pub Date : 2024-05-21 DOI: 10.1002/jnr.25342
Joseph W. Molloy, Denis Barry
{"title":"The interplay between glucose and ketone bodies in neural stem cell metabolism","authors":"Joseph W. Molloy,&nbsp;Denis Barry","doi":"10.1002/jnr.25342","DOIUrl":"10.1002/jnr.25342","url":null,"abstract":"<p>Glucose is the primary energy source for neural stem cells (NSCs), supporting their proliferation, differentiation, and quiescence. However, the high demand for glucose during brain development often exceeds its supply, leading to the utilization of alternative energy sources including ketone bodies. Ketone bodies, including β-hydroxybutyrate, are short-chain fatty acids produced through hepatic ketogenesis and play a crucial role in providing energy and the biosynthetic components for NSCs when required. The interplay between glucose and ketone metabolism influences NSC behavior and fate decisions, and disruptions in these metabolic pathways have been linked to neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Additionally, ketone bodies exert neuroprotective effects on NSCs and modulate cellular responses to oxidative stress, energy maintenance, deacetylation, and inflammation. As such, understanding the interdependence of glucose and ketone metabolism in NSCs is crucial to understanding their roles in NSC function and their implications for neurological conditions. This article reviews the mechanisms of glucose and ketone utilization in NSCs, their impact on NSC function, and the therapeutic potential of targeting these metabolic pathways in neurological disorders.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25342","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076021","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
Heterogeneity of brain extracellular matrix and astrocyte activation 脑细胞外基质和星形胶质细胞活化的异质性
IF 4.2 3区 医学
Journal of Neuroscience Research Pub Date : 2024-05-21 DOI: 10.1002/jnr.25356
Rebecca E. Huber, Courtney Babbitt, Shelly R. Peyton
{"title":"Heterogeneity of brain extracellular matrix and astrocyte activation","authors":"Rebecca E. Huber,&nbsp;Courtney Babbitt,&nbsp;Shelly R. Peyton","doi":"10.1002/jnr.25356","DOIUrl":"10.1002/jnr.25356","url":null,"abstract":"<p>From the blood brain barrier to the synaptic space, astrocytes provide structural, metabolic, ionic, and extracellular matrix (ECM) support across the brain. Astrocytes include a vast array of subtypes, their phenotypes and functions varying both regionally and temporally. Astrocytes' metabolic and regulatory functions poise them to be quick and sensitive responders to injury and disease in the brain as revealed by single cell sequencing. Far less is known about the influence of the local healthy and aging microenvironments on these astrocyte activation states. In this forward-looking review, we describe the known relationship between astrocytes and their local microenvironment, the remodeling of the microenvironment during disease and injury, and postulate how they may drive astrocyte activation. We suggest technology development to better understand the dynamic diversity of astrocyte activation states, and how basal and activation states depend on the ECM microenvironment. A deeper understanding of astrocyte response to stimuli in ECM-specific contexts (brain region, age, and sex of individual), paves the way to revolutionize how the field considers astrocyte-ECM interactions in brain injury and disease and opens routes to return astrocytes to a healthy quiescent state.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Divergent association between pain intensity and resting-state fMRI-based brain entropy in different age groups 不同年龄组的疼痛强度与基于静息态 fMRI 的大脑熵之间存在差异。
IF 4.2 3区 医学
Journal of Neuroscience Research Pub Date : 2024-05-15 DOI: 10.1002/jnr.25341
Gianpaolo Del Mauro, Landrew Samuel Sevel, Jeff Boissoneault, Ze Wang
{"title":"Divergent association between pain intensity and resting-state fMRI-based brain entropy in different age groups","authors":"Gianpaolo Del Mauro,&nbsp;Landrew Samuel Sevel,&nbsp;Jeff Boissoneault,&nbsp;Ze Wang","doi":"10.1002/jnr.25341","DOIUrl":"10.1002/jnr.25341","url":null,"abstract":"<p>Pain is a multidimensional subjective experience sustained by multiple brain regions involved in different aspects of pain experience. We used brain entropy (BEN) estimated from resting-state fMRI (rsfMRI) data to investigate the neural correlates of pain experience. BEN was estimated from rs-fMRI data provided by two datasets with different age range: the Human Connectome Project-Young Adult (HCP-YA) and the Human Connectome project-Aging (HCP-A) datasets. Retrospective assessment of experienced pain intensity was retrieved from both datasets. No main effect of pain intensity was observed. The interaction between pain and age, however, was related to increased BEN in several pain-related brain regions, reflecting greater variability of spontaneous brain activity. Dividing the sample into a young adult group (YG) and a middle age-aging group (MAG) resulted in two divergent patterns of pain–BEN association: In the YG, pain intensity was related to reduced BEN in brain regions involved in the sensory processing of pain; in the MAG, pain was associated with increased BEN in areas related to both sensory and cognitive aspects of pain experience.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Implications of environmental nanoparticles on neurodegeneration 环境纳米粒子对神经退化的影响。
IF 4.2 3区 医学
Journal of Neuroscience Research Pub Date : 2024-05-15 DOI: 10.1002/jnr.25340
Cristina Hermosillo-Abundis, Miguel A. Méndez-Rojas, Oscar Arias-Carrión
{"title":"Implications of environmental nanoparticles on neurodegeneration","authors":"Cristina Hermosillo-Abundis,&nbsp;Miguel A. Méndez-Rojas,&nbsp;Oscar Arias-Carrión","doi":"10.1002/jnr.25340","DOIUrl":"10.1002/jnr.25340","url":null,"abstract":"<p>The ubiquity of nanoparticles, sourced from both natural environments and human activities, presents critical challenges for public health. While offering significant potential for innovative biomedical applications—especially in enhancing drug transport across the blood–brain barrier—these particles also introduce possible hazards due to inadvertent exposure. This concise review explores the paradoxical nature of nanoparticles, emphasizing their promising applications in healthcare juxtaposed with their potential neurotoxic consequences. Through a detailed examination, we delineate the pathways through which nanoparticles can reach the brain and the subsequent health implications. There is growing evidence of a disturbing association between nanoparticle exposure and the onset of neurodegenerative conditions, highlighting the imperative for comprehensive research and strategic interventions. Gaining a deep understanding of these mechanisms and enacting protective policies are crucial steps toward reducing the health threats of nanoparticles, thereby maximizing their therapeutic advantages.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
The differential effects of palmitic acid and oleic acid on the metabolic response of hypothalamic astrocytes from male and female mice 棕榈酸和油酸对雌雄小鼠下丘脑星形胶质细胞代谢反应的不同影响
IF 4.2 3区 医学
Journal of Neuroscience Research Pub Date : 2024-05-14 DOI: 10.1002/jnr.25339
Roberto Collado-Perez, David Chamoso-Sánchez, Antonia García, María S. Fernández-Alfonso, Maria Jiménez-Hernáiz, Sandra Canelles, Jesús Argente, Laura M. Frago, Julie A. Chowen
{"title":"The differential effects of palmitic acid and oleic acid on the metabolic response of hypothalamic astrocytes from male and female mice","authors":"Roberto Collado-Perez,&nbsp;David Chamoso-Sánchez,&nbsp;Antonia García,&nbsp;María S. Fernández-Alfonso,&nbsp;Maria Jiménez-Hernáiz,&nbsp;Sandra Canelles,&nbsp;Jesús Argente,&nbsp;Laura M. Frago,&nbsp;Julie A. Chowen","doi":"10.1002/jnr.25339","DOIUrl":"10.1002/jnr.25339","url":null,"abstract":"<p>Diets rich in saturated fats are more detrimental to health than those containing mono- or unsaturated fats. Fatty acids are an important source of energy, but they also relay information regarding nutritional status to hypothalamic metabolic circuits and when in excess can be detrimental to these circuits. Astrocytes are the main site of central fatty acid β-oxidation, and hypothalamic astrocytes participate in energy homeostasis, in part by modulating hormonal and nutritional signals reaching metabolic neurons, as well as in the inflammatory response to high-fat diets. Thus, we hypothesized that how hypothalamic astrocytes process-specific fatty acids participates in determining the differential metabolic response and that this is sex dependent as males and females respond differently to high-fat diets. Male and female primary hypothalamic astrocyte cultures were treated with oleic acid (OA) or palmitic acid (PA) for 24 h, and an untargeted metabolomics study was performed. A clear predictive model for PA exposure was obtained, while the metabolome after OA exposure was not different from controls. The observed modifications in metabolites, as well as the expression levels of key metabolic enzymes, indicate a reduction in the activity of the Krebs and glutamate/glutamine cycles in response to PA. In addition, there were specific differences between the response of astrocytes from male and female mice, as well as between hypothalamic and cerebral cortical astrocytes. Thus, the response of hypothalamic astrocytes to specific fatty acids could result in differential impacts on surrounding metabolic neurons and resulting in varied systemic metabolic outcomes.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
IDO-1 inhibition improves outcome after fluid percussion injury in adult male rats 抑制 IDO-1 可改善成年雄性大鼠体液冲击损伤后的疗效
IF 4.2 3区 医学
Journal of Neuroscience Research Pub Date : 2024-05-06 DOI: 10.1002/jnr.25338
Marawan Sadek, Kurt R. Stover, Xiaojing Liu, Mark A. Reed, Donald F. Weaver, Aylin Y. Reid
{"title":"IDO-1 inhibition improves outcome after fluid percussion injury in adult male rats","authors":"Marawan Sadek,&nbsp;Kurt R. Stover,&nbsp;Xiaojing Liu,&nbsp;Mark A. Reed,&nbsp;Donald F. Weaver,&nbsp;Aylin Y. Reid","doi":"10.1002/jnr.25338","DOIUrl":"https://doi.org/10.1002/jnr.25338","url":null,"abstract":"<p>The enzyme indoleamine 2,3 dioxygenase 1 (IDO1) catalyzes the rate-limiting step in the kynurenine pathway (KP) which produces both neuroprotective and neurotoxic metabolites. Neuroinflammatory signals produced as a result of pathological conditions can increase production of IDO1 and boost its enzymatic capacity. IDO1 and the KP have been implicated in behavioral recovery after human traumatic brain injury (TBI), but their roles in experimental models of TBI are for the most part unknown. We hypothesized there is an increase in KP activity in the fluid percussion injury (FPI) model of TBI, and that administration of an IDO1 inhibitor will improve neurological recovery. In this study, adult male Sprague Dawley rats were subjected to FPI or sham injury and received twice-daily oral administration of the IDO1 inhibitor PF-06840003 (100 mg/kg) or vehicle control. FPI resulted in a significant increase in KP activity, as demonstrated by an increased ratio of kynurenine: tryptophan, in the perilesional neocortex and ipsilateral hippocampus 3 days postinjury (DPI), which normalized by 7 DPI. The increase in KP activity was prevented by PF-06840003. IDO1 inhibition also improved memory performance as assessed in the Barnes maze and anxiety behaviors as assessed in open field testing in the first 28 DPI. These results suggest increased KP activity after FPI may mediate neurological dysfunction, and IDO1 inhibition should be further investigated as a potential therapeutic target to improve recovery.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25338","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140844764","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
Excessive intragastric alcohol administration exacerbates hepatic encephalopathy and provokes neuronal cell death in male rats with chronic liver disease 雄性慢性肝病大鼠胃内摄入过量酒精会加重肝性脑病并导致神经细胞死亡
IF 4.2 3区 医学
Journal of Neuroscience Research Pub Date : 2024-04-29 DOI: 10.1002/jnr.25337
Farzaneh Tamnanloo, Xiaoru Chen, Mariana M. Oliveira, Mélanie Tremblay, Christopher F. Rose
{"title":"Excessive intragastric alcohol administration exacerbates hepatic encephalopathy and provokes neuronal cell death in male rats with chronic liver disease","authors":"Farzaneh Tamnanloo,&nbsp;Xiaoru Chen,&nbsp;Mariana M. Oliveira,&nbsp;Mélanie Tremblay,&nbsp;Christopher F. Rose","doi":"10.1002/jnr.25337","DOIUrl":"https://doi.org/10.1002/jnr.25337","url":null,"abstract":"<p>Hepatic encephalopathy (HE) is defined as decline in neurological function during chronic liver disease (CLD). Alcohol is a major etiological factor in the pathogenesis of fibrosis/cirrhosis and has also been documented to directly impact the brain. However, the role of alcohol in the development of HE in CLD remains unclear. Here, we investigated the impact of excessive alcohol administration on neurological deterioration in rats with CLD. Starting day 7 post-BDL surgery, rats were administered alcohol twice daily (51% v/v ethanol, 3 g/kg, via gavage) for 4 weeks. Motor coordination was assessed weekly using rotarod and anxiety-like behavior was evaluated with open field and elevated plus maze at 5 weeks. Upon sacrifice, brains were collected for western blot and immunohistochemical analyses to investigate neuronal integrity and oxidative stress status. Alcohol worsened motor coordination performance and increased anxiety-like behavior in BDL rats. Impairments were associated with decreased neuronal markers of NeuN and SMI311, increased apoptotic markers of cleaved/pro-caspase-3 and Bax/Bcl2, increased necroptosis markers of pRIP3 and pMLKL, decreased total antioxidant capacity (TAC), and increased 4-hydroxynonenal (4-HNE)modified proteins in the cerebellum of BDL-alcohol rats when compared to respective controls. Immunofluorescence confirmed the colocalization of cleaved caspase-3 and pMLKL in the granular neurons of the cerebellum of BDL-alcohol rats. Excessive alcohol consumption exacerbates HE which leads to associated apoptotic and necroptotic neuronal loss in the cerebellum of BDL-alcohol rats. Additionally, higher levels of 4-HNE and decreased TAC in the cerebellum of BDL-alcohol rats suggest oxidative stress is the triggering factor of apoptotic and necroptotic neuronal loss/injury.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"102 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.25337","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140808157","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
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