Neurochemistry international最新文献

{"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 CuCl₂ (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 CuCl₂ exposure and their silencing partially limited CuCl₂-neurodetrimental effect. Furthermore, in CuCl₂-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 CuCl₂-induced cell death, the double-transfection of siRNAs for Sp1 and Sp4, or for HD11 and HAT-p300, completely reverted the neurotoxic effect of CuCl₂. Collectively, we found that CuCl₂-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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"title":"METTL3/IGF2BP2/IκBα axis participates in neuroinflammation in Alzheimer's disease by regulating M1/M2 polarization of microglia","authors":"Ling Zhu ,&nbsp;Congyan Liu ,&nbsp;Yang Wang ,&nbsp;Xuanang Zhu ,&nbsp;Lei Wu ,&nbsp;Lvan Chen ,&nbsp;Jing Zhou ,&nbsp;Fan Wang","doi":"10.1016/j.neuint.2025.105964","DOIUrl":"10.1016/j.neuint.2025.105964","url":null,"abstract":"<div><h3>Background</h3><div>Microglia-mediated neuroinflammation is closely related to the development of Alzheimer's disease (AD). This study further elucidated the regulatory mechanism of microglia polarization in AD.</div></div><div><h3>Method</h3><div>Microglia polarization was assessed using RT-qPCR, ELISA, and immunofluorescence (IF). Western blot (WB) analyzed inflammation-related, p-tau, and apoptosis-related proteins. Neuronal damage was evaluated by immunofluorescence, and neuronal apoptosis by flow cytometry and TUNEL assay. METTL3 and IκBα expression were detected using RT-qPCR and WB. N⁶-methyladenosine (m⁶A) levels were quantified with a colorimetric assay. RNA pull-down assay examined METTL3, IGF2BP2, and IκBα mRNA binding. IGF2BP expression was assessed by RT-qPCR. Learning and memory abilities were evaluated using morris water maze (MWM) test and novel object recognition (NOR) test. Inflammation-related proteins were detected using IF.</div></div><div><h3>Results</h3><div>Stimulation with Aβ_1-42 led to microglia M1 polarization, upregulation of inflammation-related proteins, and exacerbation of neuronal injury and apoptosis, along with increased p-tau expression in neurons. METTL3/IGF2BP2 modulated IκBα m⁶A modification through binding to IκBα mRNA, enhancing its expression. Enhanced METTL3 or IGF2BP2 expression suppressed M1 polarization, inflammation, and neuronal apoptosis in microglia, reversed by knockdown of IκBα. AD model mice exhibited cognitive impairments, neuroinflammation, and elevated M1 polarization. METTL3 or IGF2BP2 overexpression improved cognitive function, reduced neuroinflammation, and inhibited M1 polarization, and this effect was similarly reversed by knockdown of IκBα.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that the METTL3/IGF2BP2/IκBα axis is involved in neuroinflammation in AD by modulating microglia M1/M2 polarization, which sheds light on the treatment of AD.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"186 ","pages":"Article 105964"},"PeriodicalIF":4.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661810","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}

{"title":"Nicotine enhances object recognition memory through activation of the medial prefrontal cortex to the perirhinal cortex pathway","authors":"Hirohito Esaki ,&nbsp;Kanta Imai ,&nbsp;Keisuke Nishikawa,&nbsp;Naoya Nishitani,&nbsp;Satoshi Deyama,&nbsp;Katsuyuki Kaneda","doi":"10.1016/j.neuint.2025.105963","DOIUrl":"10.1016/j.neuint.2025.105963","url":null,"abstract":"<div><div>Nicotine enhances recognition memory across species; however, the underlying neuronal mechanisms remain incompletely understood. Our previous study using a novel object recognition (NOR) test and electrophysiological recordings of mouse brain slices demonstrated that nicotine enhanced object recognition memory by stimulating nicotinic acetylcholine receptors in the medial prefrontal cortex (mPFC). To elucidate this further, we conducted the NOR test combined with pharmacology, chemogenetics, optogenetics, and <em>ex vivo</em> electrophysiology in male C57BL/6J mice. Chemogenetic inhibition of mPFC excitatory neurons suppressed nicotine-induced enhancement of object recognition memory, whereas their activation alone was sufficient to enhance memory. Anatomical studies indicate that the mPFC sends projections to the perirhinal cortex (PRH), a brain region involved in object recognition memory. Therefore, we focused on mPFC-PRH projections. Whole-cell patch-clamp recordings with optogenetic stimulation revealed that PRH pyramidal neurons received monosynaptic and glutamatergic inputs from the mPFC. Chemogenetic suppression of mPFC neurons projecting to the PRH blocked the nicotine-induced enhancement of object recognition memory, whereas activation of these neurons alone was sufficient to enhance memory. To achieve precise temporal control, optogenetic inhibition of the mPFC-PRH pathway during the training session blocked the effects of nicotine, and its activation alone enhanced memory. Furthermore, unilateral intra-mPFC nicotine infusion enhanced object recognition memory, and this effect was suppressed by ipsilateral intra-PRH infusion of an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist. These findings indicate that nicotine enhances object recognition memory by activating glutamatergic projections from the mPFC to PRH.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"185 ","pages":"Article 105963"},"PeriodicalIF":4.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612926","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}

{"title":"Biochemical and medical aspects of vitamin B1 research","authors":"Alexander F. Makarchikov ,&nbsp;Pierre Wins ,&nbsp;Lucien Bettendorff","doi":"10.1016/j.neuint.2025.105962","DOIUrl":"10.1016/j.neuint.2025.105962","url":null,"abstract":"<div><div>Vitamin B₁ is an indispensable food factor for the human and animal body. In animals, vitamin B₁ is found in the form of thiamine and its phosphate esters – thiamine mono-, di- and triphosphate, as well as an adenylated derivative – adenosine thiamine triphosphate. At present, the only vitamin B₁ form with biochemical functions being elucidated is thiamine diphosphate, which serves as a coenzyme for several important enzymes involved in carbohydrate, amino acid, fatty acid and energy metabolism. Here we review the latest developments in the field of vitamin B₁ research in animals. Transport, metabolism and biological role of thiamine and its derivatives are considered as well as the involvement of vitamin B₁-dependent processes in human diseases and its therapeutic issues, a field that has gained momentum with several important recent developments.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"185 ","pages":"Article 105962"},"PeriodicalIF":4.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584155","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}

{"title":"Repeated administration of esketamine ameliorates mechanical allodynia in mice with chemotherapy-induced peripheral neuropathy: A role of gut microbiota and metabolites","authors":"Wei-wei Luan ,&nbsp;Han-wen Gu ,&nbsp;Di Qiu ,&nbsp;Xin Ding ,&nbsp;Pan-miao Liu ,&nbsp;Kenji Hashimoto ,&nbsp;Jian-jun Yang ,&nbsp;Xing-ming Wang","doi":"10.1016/j.neuint.2025.105961","DOIUrl":"10.1016/j.neuint.2025.105961","url":null,"abstract":"<div><div>Chemotherapy-induced peripheral neuropathy (CIPN) severely diminishes the quality of life for cancer survivors, yet effective treatments remain scarce. Esketamine, a commonly used anesthetic, has demonstrated neuroprotective effects by restoring gut microbiome dysbiosis. In this study, we investigated the impact of esketamine on nociceptive sensitivity in a mouse model of CIPN and explored the potential involvement of the gut microbiome. In mice treated with oxaliplatin, repeated esketamine doses (in contrast to a single dose) significantly improved the paw withdrawal threshold (PWT). Western blot and qPCR analyses further revealed that repeated esketamine administration markedly reduced microglial activation and neuroinflammation in the dorsal root ganglion (DRG), underscoring its potent anti-inflammatory properties. Moreover, fecal 16S rRNA analysis indicated that esketamine partially restored the abnormal gut microbiota composition (β-diversity). Plasma metabolome analysis showed that repeated esketamine treatment significantly lowered the elevated levels of 6H-indolo[2,3-b]quinoline and restored the reduced levels of (3-exo)-3-[3-methyl-5-(1-methylethyl)-4H-1,2,4-triazol-4-yl]-8-azabicyclo[3.2.1]octane observed in oxaliplatin-treated mice. In addition, fecal microbiota transplantation from esketamine-treated CIPN mice notably improved both the diminished PWT and DRG neuroinflammation in oxaliplatin-treated mice. Collectively, these findings suggest that repeated esketamine administration may alleviate mechanical allodynia in CIPN mice by modulating neuroinflammation, gut microbiota, and associated metabolites.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"185 ","pages":"Article 105961"},"PeriodicalIF":4.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584167","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}