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Non-canonical STAT3 pathway induces alterations of mitochondrial dynamic proteins in the hippocampus of an LPS-induced murine neuroinflammation model
IF 4.4 3区 医学
Neurochemistry international Pub Date : 2025-04-08 DOI: 10.1016/j.neuint.2025.105979
Périne Millot , Laurine Duquesne , Carine San , Baptiste Porte , Claire Pujol , Benoit Hosten , Jacques Hugon , Claire Paquet , François Mouton-Liger
{"title":"Non-canonical STAT3 pathway induces alterations of mitochondrial dynamic proteins in the hippocampus of an LPS-induced murine neuroinflammation model","authors":"Périne Millot ,&nbsp;Laurine Duquesne ,&nbsp;Carine San ,&nbsp;Baptiste Porte ,&nbsp;Claire Pujol ,&nbsp;Benoit Hosten ,&nbsp;Jacques Hugon ,&nbsp;Claire Paquet ,&nbsp;François Mouton-Liger","doi":"10.1016/j.neuint.2025.105979","DOIUrl":"10.1016/j.neuint.2025.105979","url":null,"abstract":"<div><div>The activation of STAT3 is a crossroads of cellular regulation, induced in its canonical pathway by phosphorylation on a critical tyrosine residue (Y705). The existence of a STAT3 non-canonical signaling mechanisms, induced by phosphorylation at serine 727 (S727), has been recently identified in vitro. After cytoplasmic activation, non-canonical STAT3 could move to the level of mitochondria-endoplasmic reticulum contacts (MERCs).</div><div>We have previously shown that LPS injections in mouse model induce STAT3 canonical pathway, leading to its nuclear translocation and to neuroinflammation. However, the effects of LPS on activation of the non-canonical pathway and its consequences on protein complexes of MERCs remain to be determined. In an <em>in vivo</em> LPS mouse model, we found that systemic inflammation induces in hippocampus the non-canonical STAT3 pathway. LPS-induced STAT3 affects specifically MERC protein BAP31, and that of a mitochondrial membrane protein known to interact with it, TOM40. These findings shed light on the role of STAT3 on mitochondrial – endoplasmic reticulum interaction under inflammatory conditions, offering new perspectives for targeting mitochondrial function and STAT3 activation in disease contexts.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"186 ","pages":"Article 105979"},"PeriodicalIF":4.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815987","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
Illustrating the distribution and metabolic regulatory effects of nuciferine by mass spectrometry imaging and spatial metabolomics
IF 4.4 3区 医学
Neurochemistry international Pub Date : 2025-04-07 DOI: 10.1016/j.neuint.2025.105977
Guangyuan Liu , Yiying Wu , Liangyu Pan , Qian Wang , Yuyu Zhang , Jingwen Yan , Panpan Zhang , Wei Zhang , Dezhi Kong
{"title":"Illustrating the distribution and metabolic regulatory effects of nuciferine by mass spectrometry imaging and spatial metabolomics","authors":"Guangyuan Liu ,&nbsp;Yiying Wu ,&nbsp;Liangyu Pan ,&nbsp;Qian Wang ,&nbsp;Yuyu Zhang ,&nbsp;Jingwen Yan ,&nbsp;Panpan Zhang ,&nbsp;Wei Zhang ,&nbsp;Dezhi Kong","doi":"10.1016/j.neuint.2025.105977","DOIUrl":"10.1016/j.neuint.2025.105977","url":null,"abstract":"<div><div>Nuciferine has been widely used in traditional Chinese medicine compound preparations and natural edible resources. Most current studies have concentrated on its lipid-lowering and weight-loss effects, while relatively few have explored its impact on central nervous system disorders. To investigate the effects of nuciferine on the nervous system and its potential pharmacological mechanisms, we mapped the distribution of nuciferine and its key metabolites in brain microregions and major organs of mice using air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI). Nuciferine was found to be distributed throughout the brain, particularly in the prefrontal cortex and hippocampus. Additionally, nuciferine was detected in several peripheral organs, including the heart, liver, kidneys, and spleen. We also identified the distribution of a major demethylated metabolite (M1), which correlated with the localization of the CYP1A2 enzyme. Metabolomic analysis revealed that nuciferine significantly alters purine metabolism, specifically increasing adenosine levels while decreasing xanthine and hypoxanthine. This metabolic shift suggests a potential enhancement of neuroinhibitory effects, contributing to nuciferine's sedative, hypnotic, and analgesic properties. These findings provide novel insights into the neuropharmacological mechanisms of nuciferine.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"186 ","pages":"Article 105977"},"PeriodicalIF":4.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823811","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
Mechanism of Tau protein incorporation into exosomes via cooperative recognition of KFERQ-like motifs by LAMP2A and HSP70
IF 4.4 3区 医学
Neurochemistry international Pub Date : 2025-04-03 DOI: 10.1016/j.neuint.2025.105976
Shan Xu , Kangyan Liu , Shiyan Qian , Jingying Wu , Jialing Hu , Dongming Zhou , Tingting Zheng
{"title":"Mechanism of Tau protein incorporation into exosomes via cooperative recognition of KFERQ-like motifs by LAMP2A and HSP70","authors":"Shan Xu ,&nbsp;Kangyan Liu ,&nbsp;Shiyan Qian ,&nbsp;Jingying Wu ,&nbsp;Jialing Hu ,&nbsp;Dongming Zhou ,&nbsp;Tingting Zheng","doi":"10.1016/j.neuint.2025.105976","DOIUrl":"10.1016/j.neuint.2025.105976","url":null,"abstract":"<div><div>Aggregates of the tau protein is a well-known hallmark of Alzheimer's disease (AD) and other Tauopathies, such as Frontotemporal dementia (FTD). Tau can be propagated between nerve cells or brain areas, similar as 'seed'. As a member of small extracellular vesicles, exosomes may act as one of the most important 'seeding machines', disseminating toxic tau and phosphorylated tau proteins between cells and thereby amplifying their neurotoxic effects. Therefore, exploring the underlying mechanisms of Tau loading into exosomes is of great importance. In this study, human P301L tau transfections were established in SH-SY5Y cells (SY5Y-EGFP-TauP301L cells). The content of membrane protein LAMP2A and HSP70 proteins was significantly increased in the SY5Y-EGFP-Tau P301L cells compared to control group. Tau containing KFERQ-like motifs pentapeptide interact with LAMP2A and HSP70, forming a multi-protein complex, which can be loaded into a subpopulation of exosomes. Moreover, knockout of LAMP2A significantly reduced the content of Tau protein in exosomes obtained from SY5Y-EGFP-Tau P301L cells. Thus, exosome-mediated secretion of tau protein may depend on the formation of multi-protein (KFERQ-like motif pentapeptide in tau,LAMP2A and HSP70) complex. These findings revealed the presence of a novel mechanism by which release of tau through exosome secretion pathway and that LAMP2A may play an important role in the regulation of exosome-mediated secretion of tau, which may become a potential therapeutic target for AD or other Tauopathies.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"186 ","pages":"Article 105976"},"PeriodicalIF":4.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787642","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
Sp4/HD11 and Sp1/HAT-p300 complexes induce apoptotic cell death in CuCl2-treated neurons by modulating histone acetylation on BCL-W and BAX promoters
IF 4.4 3区 医学
Neurochemistry international Pub Date : 2025-04-02 DOI: 10.1016/j.neuint.2025.105973
Silvia Ruggiero , Natascia Guida , Luigi Mascolo , Angelo Serani , Anna Ferrante , Francesca Galasso , Luca Sanguigno , Erica Piemonte , Elvira De Rosa , Paolo Montuori , Maria Triassi , Gianfranco Di Renzo , Mario Galgani , Luigi Formisano
{"title":"Sp4/HD11 and Sp1/HAT-p300 complexes induce apoptotic cell death in CuCl2-treated neurons by modulating histone acetylation on BCL-W and BAX promoters","authors":"Silvia Ruggiero ,&nbsp;Natascia Guida ,&nbsp;Luigi Mascolo ,&nbsp;Angelo Serani ,&nbsp;Anna Ferrante ,&nbsp;Francesca Galasso ,&nbsp;Luca Sanguigno ,&nbsp;Erica Piemonte ,&nbsp;Elvira De Rosa ,&nbsp;Paolo Montuori ,&nbsp;Maria Triassi ,&nbsp;Gianfranco Di Renzo ,&nbsp;Mario Galgani ,&nbsp;Luigi Formisano","doi":"10.1016/j.neuint.2025.105973","DOIUrl":"10.1016/j.neuint.2025.105973","url":null,"abstract":"<div><div>Copper is a metal physiologically present in the brain that becomes neurotoxic at high concentrations; on the other hand, pharmacological inhibition of Histone Deacetylases (HDs) or of Histone Acetyltransferases (HATs) reduce neuronal death caused by several neurotoxicants. Herein, we found that CuCl<sub>2</sub> (300 μM in SH-SY5Y cells or 100 μM in cortical neurons) determined apoptotic cell death, that was counteracted by the class IV HDs inhibitor Mocetinostat (MOCE) and by the HAT-p300 inhibitor C646, but not by the class I and II HDs inhibitors. Interestingly, HD11 and HAT-p300 protein levels increased after both 12 and 24 h of CuCl<sub>2</sub> exposure and their silencing partially limited CuCl<sub>2</sub>-neurodetrimental effect. Furthermore, in CuCl<sub>2</sub>-treated cells the transcriptional factor Sp4 co-localized with HD11 on the promoter of anti-apoptotic gene BCL-W, determining histone H3 hypo-acetylation, a marker of gene repression. Contrarily, Sp1 co-localized with HAT-p300 on the pro-apoptotic gene BAX, determining histone H4 hyper-acetylation, a hallmark of transcriptional activation. In addition, siRNA against Sp4 prevented HD11 binding on BCL-W promoter and its consequent down-regulation, whereas Sp1 knocking-down, by reducing HAT-p300 interaction on BAX gene promoter counteracted its up-regulation. Importantly, while the single knocking-down of Sp1, Sp4, HD11 and HAT-p300 partially mitigated CuCl<sub>2</sub>-induced cell death, the double-transfection of siRNAs for Sp1 and Sp4, or for HD11 and HAT-p300, completely reverted the neurotoxic effect of CuCl<sub>2</sub>. Collectively, we found that CuCl<sub>2</sub>-induced neuronal apoptosis is determined by the binding of Sp1/HAT-p300 and of Sp4/HD11 transcriptional complexes on the BAX and BCL-W gene, respectively, unraveling a new pathway involved in Copper-induced neurotoxicity.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"186 ","pages":"Article 105973"},"PeriodicalIF":4.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785579","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
Suppression of KDM5C mitigates the symptoms of Alzheimer's disease by up-regulating BDNF expression
IF 4.4 3区 医学
Neurochemistry international Pub Date : 2025-04-01 DOI: 10.1016/j.neuint.2025.105975
Jingjing Han , Rui Hong , Cong Cao , Lina Zhang , Ao Sun , Yufei Li , Yinxiu Chi , Linlin Zhang , Ya Yang , Xuebin Qu
{"title":"Suppression of KDM5C mitigates the symptoms of Alzheimer's disease by up-regulating BDNF expression","authors":"Jingjing Han ,&nbsp;Rui Hong ,&nbsp;Cong Cao ,&nbsp;Lina Zhang ,&nbsp;Ao Sun ,&nbsp;Yufei Li ,&nbsp;Yinxiu Chi ,&nbsp;Linlin Zhang ,&nbsp;Ya Yang ,&nbsp;Xuebin Qu","doi":"10.1016/j.neuint.2025.105975","DOIUrl":"10.1016/j.neuint.2025.105975","url":null,"abstract":"<div><div>Histone methylation, a common form of chromatin remodeling, has been found to be associated with various neurological and cognitive disorders. However, little is known about how this mechanism contributes to the onset and progression of Alzheimer's disease (AD). Here, we found that lysine demethylase 5C (KDM5C), a histone H3 lysine 4 di- and tri-methyl (H3K4me2/3)-specific demethylase encoded by an X-linked mental retardation-related gene, displayed a progressive increase in the hippocampus with age in 3 × Tg-AD mice. Suppression of KDM5C partially mitigated the cognitive decline according to water maze, Y maze, and novel object recognition tests. In addition, significantly decreased amyloid plaques, enhanced long-term potentiation (LTP), and up-regulated expression of <em>synaptic proteins</em> were observed in KDM5C knockdown 3 × Tg-AD mice. Mechanistically, suppression of KDM5C could promote the expression of brain-derived neurotrophic factor (BDNF) to partially protect hippocampal neurons from beta-amyloid damage. In the promoter region of <em>Bdnf</em>, KDM5C was bound to the repressor element-1 (RE-1) motif to reduce the nearby H3K4me3 level and inhibit gene transcription. Mutations in the RE-1 motif reversed the inhibitory effect of KDM5C. Our results emphasize that KDM5C excess is one of the reasons for the onset and progression of AD and that suppression of KDM5C in the hippocampus should be considered a potential therapeutic target to ameliorate cognitive impairment and pathological symptoms in AD.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"186 ","pages":"Article 105975"},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778642","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
Chronic inflammatory pain suppresses alcohol intake and accumbal dopamine response
IF 4.4 3区 医学
Neurochemistry international Pub Date : 2025-04-01 DOI: 10.1016/j.neuint.2025.105974
Javier Cuitavi , Ana Riera-Calabuig , Yolanda Campos-Jurado , Jesús D. Lorente , María de Jorge , Ana Polache , Lucía Hipólito
{"title":"Chronic inflammatory pain suppresses alcohol intake and accumbal dopamine response","authors":"Javier Cuitavi ,&nbsp;Ana Riera-Calabuig ,&nbsp;Yolanda Campos-Jurado ,&nbsp;Jesús D. Lorente ,&nbsp;María de Jorge ,&nbsp;Ana Polache ,&nbsp;Lucía Hipólito","doi":"10.1016/j.neuint.2025.105974","DOIUrl":"10.1016/j.neuint.2025.105974","url":null,"abstract":"<div><div>Alcohol use disorders (AUDs) are influenced by factors that initiate, maintain, and/or induce relapse. Chronic pain is both a risk factor for and consequence of AUD, sharing neurological pathways that affect the mesolimbic dopaminergic system. This study examines how inflammatory pain impacts long-term alcohol intake and mesolimbic dopamine transmission in alcohol-naïve rats. Inflammatory pain was induced in eight-week-old Sprague Dawley rats using complete Freund adjuvant (CFA), while controls received saline. Two protocols were followed: one group had continuous access to 20 % ethanol for one month (n = 10/sex), and the second group for three months (n = 8/sex) in a two-bottle choice paradigm. Mechanical nociception was assessed weekly using the Von Frey test. Dopamine levels in the nucleus accumbens core were measured through microdialysis during the final 1.5 months of ethanol exposure in the second cohort. Due to experimental limitations animals underwent microdialysis at different time points after alcohol was firstly introduced, this was done in a balanced manner by alternating sex and group. After a month of alcohol exposure, rats showed no differences in alcohol consumption. However, from the second month until the end, rats exhibited a non-sex-dependent decrease in alcohol intake, significantly lower in CFA-animals. This reduction was accompanied by a blunted ethanol-evoked dopamine release in the nucleus accumbens. Moreover, low mechanical nociception was maintained until the end of the experiment in CFA-animal. These findings provide insights into the effect of pain on alcohol-elicited neurochemical responses and drinking behaviour, showing how pain alters dopamine response to alcohol, affecting drinking patterns and prolonging nociception from CFA.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"186 ","pages":"Article 105974"},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768121","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
Potential roles of inhalation aromatherapy on stress-induced depression by inhibiting inflammation in the peripheral olfactory system
IF 4.4 3区 医学
Neurochemistry international Pub Date : 2025-03-28 DOI: 10.1016/j.neuint.2025.105967
Hongxiu Song , Aihong Yang , Yang Wang , Rui Xu , Wei Hu
{"title":"Potential roles of inhalation aromatherapy on stress-induced depression by inhibiting inflammation in the peripheral olfactory system","authors":"Hongxiu Song ,&nbsp;Aihong Yang ,&nbsp;Yang Wang ,&nbsp;Rui Xu ,&nbsp;Wei Hu","doi":"10.1016/j.neuint.2025.105967","DOIUrl":"10.1016/j.neuint.2025.105967","url":null,"abstract":"<div><div>According to principles of Traditional Chinese Medicine, the nose is the passage for exogenous evil to invade the body, while essential or volatile oils extracted from herbs have the effects of dispelling melancholy, repelling foulness, and resuscitation with aromatics. Inhalation aromatherapy can target the brain and has a potential therapeutic effect on mood disorders. However, in particular, the mechanism of the effect of inhalation aromatherapy on the olfactory mucosa (OM) of the nasal cavity at the peripheral level, the first step in olfactory detection, where olfactory sensory neurons (OSNs) relay information to brain for signal processing, remains unclear. Here, we examined the roles of inhalation aromatherapy with compound essential oils derived from Bergamot, Peppermint and Rosa rugose on chronic unpredictable mild stress (CUMS)-induced depression and explored potential therapeutic targets in the peripheral OM. We found that inhalation aromatherapy effectively ameliorated CUMS-induced depression and olfactory dysfunction in rats. Strikingly, inhalation aromatherapy improved pathological changes, significantly reduced apoptosis levels, and promoted olfactory neurogenesis in the OM, which may contribute to the beneficial effects on the olfactory function of depressed rats. Further, inhalation aromatherapy significantly may reverse inflammation levels in the OM through Sirt1/FKBP5/GR/NF-κB signaling pathway, and prevented neuroinflammation in other parts of the olfactory system such as the hippocampus and prefrontal cortex, which may play a role in the olfactory impairments in rats with depression. Collectively, we have demonstrated that inhalation aromatherapy could efficiently prevent the local inflammatory responses in the OM of CUMS depression model rats. These findings provide new insights into the treatment of depression with aromatherapy, as well as new concept for the identification of novel antidepressant strategies.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"186 ","pages":"Article 105967"},"PeriodicalIF":4.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750430","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 C. elegans glutamate transporters GLT-4 and GLT-5 regulate protein expression, behavior, and lifespan
IF 4.4 3区 医学
Neurochemistry international Pub Date : 2025-03-25 DOI: 10.1016/j.neuint.2025.105966
Grace J. Bronstone , Moriah Harton , Maya Muldowney , James Reigle , Adam J. Funk , Sinead M. O'Donovan , Robert E. McCullumsmith , Deborah E. Bauer
{"title":"The C. elegans glutamate transporters GLT-4 and GLT-5 regulate protein expression, behavior, and lifespan","authors":"Grace J. Bronstone ,&nbsp;Moriah Harton ,&nbsp;Maya Muldowney ,&nbsp;James Reigle ,&nbsp;Adam J. Funk ,&nbsp;Sinead M. O'Donovan ,&nbsp;Robert E. McCullumsmith ,&nbsp;Deborah E. Bauer","doi":"10.1016/j.neuint.2025.105966","DOIUrl":"10.1016/j.neuint.2025.105966","url":null,"abstract":"<div><div>Glutamate transporters are important for regulating extracellular glutamate levels, impacting neural function and metabolic homeostasis. This study explores the behavioral, lifespan, and proteomic profiles in <em>Caenorhabditis elegans</em> strains with either <em>glt-4</em> or <em>glt-5</em> null mutations, highlighting contrasting phenotypes. Δ<em>glt-4</em> mutants displayed impaired mechanosensory and chemotactic responses, reduced lifespans, and decreased expression levels of ribosomal proteins and chaperonins involved in protein synthesis and folding. In contrast, Δ<em>glt-5</em> mutants displayed heightened chemorepulsion, extended lifespans, and upregulation of mitochondrial pyruvate carriers and cytoskeletal proteins. Proteomic profiling via mass spectrometry identified 53 differentially expressed proteins in Δ<em>glt-4</em> mutants and 45 in Δ<em>glt-5</em> mutants. Δ<em>glt-4</em> mutants showed disruptions in ribonucleoprotein complex organization and translational processes, including downregulation of glycogen phosphorylase and V-type ATPase subunits, while Δ<em>glt-5</em> mutants revealed altered metabolic protein expression, such as increased levels of mitochondrial pyruvate carriers and decreased levels of fibrillarin and ribosomal proteins. Gene ontology enrichment analysis highlighted differential regulation of protein biosynthesis and metabolic pathways between the strains. Overall, these findings underscore the distinct, tissue-specific roles of GLT-4 and GLT-5 in <em>C. elegans</em>, with broader implications for glutamate regulation and systemic physiology. The results also reinforce the utility of <em>C. elegans</em> as a model for studying glutamate transporters' impact on behavior, longevity, and proteostasis.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"186 ","pages":"Article 105966"},"PeriodicalIF":4.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724325","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
Morphine self-administration decreases intrinsic excitability of accumbal medium spiny neurons and suppresses the innate immune system in male Wistar rats
IF 4.4 3区 医学
Neurochemistry international Pub Date : 2025-03-22 DOI: 10.1016/j.neuint.2025.105965
Louise Adermark , Davide Cadeddu , Erika Lucente , Klara Danielsson , Bo Söderpalm , Mia Ericson
{"title":"Morphine self-administration decreases intrinsic excitability of accumbal medium spiny neurons and suppresses the innate immune system in male Wistar rats","authors":"Louise Adermark ,&nbsp;Davide Cadeddu ,&nbsp;Erika Lucente ,&nbsp;Klara Danielsson ,&nbsp;Bo Söderpalm ,&nbsp;Mia Ericson","doi":"10.1016/j.neuint.2025.105965","DOIUrl":"10.1016/j.neuint.2025.105965","url":null,"abstract":"<div><h3>Introduction</h3><div>Morphine alleviates severe pain but is addictive and associated with weakened immune system. Interestingly, the immunosuppressive effects have been linked to central circuits including the nucleus accumbens shell (NAc), suggesting that there might be a direct link between reward processing in the NAc and weakened immune system. The overall aim with this study was to assess the impact displayed by morphine self-administration on neuroplasticity in the NAc shell and circulating white blood cells.</div></div><div><h3>Methods</h3><div>Wistar rats received morphine injections over ten days, and locomotor activity was monitored. Next, morphine self-administration, and relapse drinking after forced abstinence, were assessed. Lastly, electrophysiological recordings were conducted in the NAc <em>ex vivo</em> to define neurophysiological adaptations, and hematological analysis were conducted in parallel.</div></div><div><h3>Results</h3><div>While ten days of morphine injections were not sufficient to affect morphine self-administration, behavioral sensitization to the locomotor stimulatory properties of morphine was observed and further correlated with the amount of morphine consumed following forced abstinence. Electrophysiological slice recordings demonstrated no effect on excitatory neurotransmission, but the intrinsic excitability of NAc neurons was significantly depressed compared to water drinking controls. In addition, hematological analysis demonstrated a significant decline in the number of white blood cells, especially monocytes and neutrophils, while erythrocytes were not affected. The amount of circulating white blood cells further correlated with morphine intake, but not with neurophysiological parameters.</div></div><div><h3>Conclusion</h3><div>The data presented here demonstrates that morphine self-administration produces accumbal neuroplasticity and biological transformations that could contribute to the addictive and immunosuppressive properties of morphine.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"186 ","pages":"Article 105965"},"PeriodicalIF":4.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697504","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
METTL3/IGF2BP2/IκBα axis participates in neuroinflammation in Alzheimer's disease by regulating M1/M2 polarization of microglia
IF 4.4 3区 医学
Neurochemistry international Pub Date : 2025-03-17 DOI: 10.1016/j.neuint.2025.105964
Ling Zhu , Congyan Liu , Yang Wang , Xuanang Zhu , Lei Wu , Lvan Chen , Jing Zhou , Fan Wang
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