Neuroscience Letters最新文献_第9页

C1ql3 promotes cognitive flexibility behavior in mice C1ql3促进小鼠的认知灵活性行为。

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-06-18 DOI: 10.1016/j.neulet.2025.138305

Keaven Caro , Trevor Religa , Shahnawaz Alam , Mark H. Cristino , Maya Preibisz-Kamat , James R. Rybczyk , Hiu W. Cheung , Maksym V. Ugrak , Timothy Spellman , David C. Martinelli

引用次数: 0

Inhibition of the nucleus accumbens core with DREADDs after acute and repeated exposure to oxycodone reduces locomotor activity in female but not male Rattus norvegicus 急性和反复暴露于氧可酮后，对雌性褐家鼠伏隔核的抑制可降低雌性褐家鼠的运动活性，但对雄性褐家鼠没有作用

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-06-18 DOI: 10.1016/j.neulet.2025.138304

Lenah C. Midani , Julie S. Jesurum , Megan G. Bachant, Fair M. Vassoler

{"title":"Inhibition of the nucleus accumbens core with DREADDs after acute and repeated exposure to oxycodone reduces locomotor activity in female but not male Rattus norvegicus","authors":"Lenah C. Midani , Julie S. Jesurum , Megan G. Bachant, Fair M. Vassoler","doi":"10.1016/j.neulet.2025.138304","DOIUrl":"10.1016/j.neulet.2025.138304","url":null,"abstract":"<div><div>Opioid use disorder affects both men and women, but significant sex differences exist in addiction vulnerability and progression. The nucleus accumbens (NAc) plays a critical role in drug reward and motor outputs, yet its sex-specific functions in opioid response remain poorly understood. We investigated the role of the NAc in acute and repeated oxycodone response using chemogenetics in male and female Sprague Dawley rats. Inhibitory DREADDs (hM4D(Gi)) or control vectors were injected into the NAc core. Rats received oxycodone (1 mg/kg, i.p.) or saline for 5 consecutive days with locomotor activity monitoring. Following a 7-day drug-free period, all rats received oxycodone challenge (1 mg/kg, i.p.) with clozapine-N-oxide (CNO, 3 mg/kg) to activate DREADD-mediated inhibition. Results revealed sex differences in both baseline and drug-induced locomotor activity, with females showing consistently higher activity in response to oxycodone than males across all sessions. Chemogenetic inhibition of the NAc significantly reduced locomotor activity in females but not males during challenge conditions, indicating sex-specific NAc involvement in the opioid response at this dose. These findings reveal sex differences in NAc involvement in acute and chronic oxycodone induced locomotor activity. Our results underscore the need for sex-specific considerations in addiction research.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"863 ","pages":"Article 138304"},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cocaine conditioning promotes persistent inhibition of GABAergic transmission in the mouse ventral hippocampal CA1 region 可卡因调节促进小鼠海马腹侧CA1区gaba能传递的持续抑制

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-06-17 DOI: 10.1016/j.neulet.2025.138301

Kyle A. Brown , John J. Wagner

{"title":"Cocaine conditioning promotes persistent inhibition of GABAergic transmission in the mouse ventral hippocampal CA1 region","authors":"Kyle A. Brown , John J. Wagner","doi":"10.1016/j.neulet.2025.138301","DOIUrl":"10.1016/j.neulet.2025.138301","url":null,"abstract":"<div><div>Millions of individuals globally meet the current diagnostic criteria for cocaine use disorder (CUD), and cocaine misuse contributes to thousands of overdose deaths every year in the United States. Current hypotheses suggest that cocaine misuse imparts a diminished ability for synaptic plasticity (i.e., drug-induced metaplasticity). This metaplasticity impairs adaptive learning, which has been proposed to contribute to the likelihood of cocaine relapse. Delineating plasticity processes that mediate drug-seeking behavior can facilitate the development of therapeutic interventions for CUD. We used behavioral pharmacology and <em>ex vivo</em> patch-clamp electrophysiology to test the hypothesis that escalating cocaine doses elicit long-lasting, drug-seeking behavior that is correlated with a persisting decrease of GABAergic transmission in the mouse ventral hippocampus (vH) CA1 region. We found that noncontingent cocaine conditioning reduced the amplitude of evoked inhibitory postsynaptic currents measured from vH CA1 pyramidal cells 4–5 weeks after the last dose, suggesting sustained synaptic disinhibition. The magnitude of drug-seeking behavior observed 4 weeks, but not 1 day, after cocaine abstinence predicted the extent of synaptic disinhibition. Persisting inhibition of GABAergic transmission occurred in the absence of altered IPSC kinetics. We conclude that cocaine conditioning evokes a progressive metaplasticity that persistently shifts the GABAergic tone of the vH CA1 region, and these synaptic actions are correlated with long-lasting drug-seeking behavior in mice. Our results suggest that targeting metaplastic processes that modulate vH neuronal excitability represents a promising therapeutic strategy for relieving symptoms associated with CUD.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"863 ","pages":"Article 138301"},"PeriodicalIF":2.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anodal transcranial direct current stimulation of cerebellum relieves motion sickness by reducing the release of acetylcholine 经颅阳极直流电刺激小脑通过减少乙酰胆碱的释放来缓解晕动病。

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-06-14 DOI: 10.1016/j.neulet.2025.138303

Niu Deng , Yihong Long , Cong Li , Yu Chen , Xiaoyu Zhang , Wei Li

{"title":"Anodal transcranial direct current stimulation of cerebellum relieves motion sickness by reducing the release of acetylcholine","authors":"Niu Deng , Yihong Long , Cong Li , Yu Chen , Xiaoyu Zhang , Wei Li","doi":"10.1016/j.neulet.2025.138303","DOIUrl":"10.1016/j.neulet.2025.138303","url":null,"abstract":"<div><div>Motion sickness (MS) is a condition caused by conflicts between motion sensors and past visual or motion memories, leading to discomfort with symptoms like hypolocomotion, low body temperature, poor appetite, and nausea. Previous studies have shown that the cerebellum is closely related to the occurrence of MS. In the present study, we aimed to evaluate the potential therapeutic effects of transcranial direct current stimulation (tDCS) of cerebellum on MS. The motion sickness index and the rotarod motor performance test were used to assess the motion sickness symptoms and motor learning in mice. Our results showed that tDCS was effective in reducing the motion sickness index in rotation-induced MS mice, as well as in reversing the rotation-induced impairment in rotarod motor learning. To understand the potential underlying mechanism, we used two-photon microimaging to monitor the release of acetylcholine in the cerebellum. Our results showed a significant increase in acetylcholine release in the cerebellum after rotation. Furthermore, anodal tDCS (a-tDCS) not only counteracted rotation-induced increase of acetylcholine in MS mice but also reduced the level of acetylcholine in static control mice. Together, these findings indicate that anodal transcranial direct current stimulation alleviates symptoms associated with motion sickness, which may be related to the reduction of acetylcholine release in the cerebellum.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"863 ","pages":"Article 138303"},"PeriodicalIF":2.5,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The shallow water test (SWT) as a novel behavioral paradigm to measure anxiety- and despair-like states in zebrafish 浅水测试（SWT）作为一种新的行为范式来测量斑马鱼的焦虑和绝望状态。

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-06-14 DOI: 10.1016/j.neulet.2025.138302

Mariana L. Müller , Angela E. Uchoa , Laura Blanco , Kimberly Fontoura , Rossano M. Silva , Julia Canzian , Barbara D. Fontana , Denis B. Rosemberg

{"title":"The shallow water test (SWT) as a novel behavioral paradigm to measure anxiety- and despair-like states in zebrafish","authors":"Mariana L. Müller , Angela E. Uchoa , Laura Blanco , Kimberly Fontoura , Rossano M. Silva , Julia Canzian , Barbara D. Fontana , Denis B. Rosemberg","doi":"10.1016/j.neulet.2025.138302","DOIUrl":"10.1016/j.neulet.2025.138302","url":null,"abstract":"<div><div>Affective disorders represent psychiatric conditions characterized by mood and emotional dysregulations, with depression and anxiety being among the most prevalent and frequently co-occurring. Depressive- and anxiety-related disorders can be associated with monoaminergic dysfunction and dysregulation of the GABAergic system. Stress plays a crucial role in the development and progression of these disorders, contributing to neurochemical disbalances. Because despair, a core symptom of depression, lacks well-established paradigms in zebrafish models based on naturalistic conditions, our goal was to report the use of the shallow water test (SWT) as a novel paradigm to assess despair-like behavior in zebrafish when placed in an unescapable shallow water environment. Basically, we exposed zebrafish to two distinct aversive conditions: mild electric shock (ES) as a physical stimulation or the conspecific alarm substance (CAS) as a naturalistic chemical cue (Experiment 1); and tested two pharmacological interventions: fluoxetine and diazepam (Experiment 2). Both stressors significantly reduced distance traveled, absolute turn angle, and average velocity, but only CAS increased the latency to mobility. While diazepam increased distance traveled, maximum speed, and average velocity, fluoxetine had no significant effects. Overall, these findings suggest the SWT as a sensitive and reliable tool for evaluating affective-like states in zebrafish, with implications for translational neurobehavioral research on affective disorders and potential therapeutic interventions.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"862 ","pages":"Article 138302"},"PeriodicalIF":2.5,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CB1 receptor antagonism reverses social and cognitive deficits induced by repeated exposure to distressed conspecifics in rats CB1受体拮抗剂可逆转大鼠反复暴露于痛苦同种动物引起的社会和认知缺陷。

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-06-10 DOI: 10.1016/j.neulet.2025.138299

Fatemeh Rahimi Shourmasti , Seyedeh Masoumeh Seyedhosseini Tamijani , Raheleh Rafaiee , Mehdi Khodamoradi , Mohammad Shabani , Fatemeh Mohammadi , Abolhassan Ghaderi , Hamed Ghazvini

{"title":"CB1 receptor antagonism reverses social and cognitive deficits induced by repeated exposure to distressed conspecifics in rats","authors":"Fatemeh Rahimi Shourmasti , Seyedeh Masoumeh Seyedhosseini Tamijani , Raheleh Rafaiee , Mehdi Khodamoradi , Mohammad Shabani , Fatemeh Mohammadi , Abolhassan Ghaderi , Hamed Ghazvini","doi":"10.1016/j.neulet.2025.138299","DOIUrl":"10.1016/j.neulet.2025.138299","url":null,"abstract":"<div><div>Empathy is a behavioral phenomenon characterized by the capacity to share in another individual’s distressing experiences, including pain, discrimination, and social rejection. The cannabinoid system, recognized as one of the brain’s neuromodulatory systems, appears to play a significant role in social and prosocial behaviors, particularly in the context of empathy. This study aimed to investigate the potential role of the cannabinoid system in mediating empathic pain and behavior, an area that has not been thoroughly explored to date. To this end, an empathic pain model was employed, wherein pain was socially transmitted from a sibling demonstrator, who received five formalin injections, to a sibling observer. Naïve observer rats were administered either the cannabinoid type 1 receptor (CB1R) antagonist rimonabant (1 mg/kg, i.p.) or the CB1R agonist WIN 55,212–2 (WIN; 3 mg/kg, i.p.) 30 min prior to behavioral assessments. The animals were subsequently evaluated using tail-flick and social interaction tasks. The behavioral findings revealed that both the demonstrator and observer groups exhibited significant increases in hyperalgesia and impairments in social memory. Notably, the administration of rimonabant, but not WIN, partially restored cognitive functions and induced analgesia in the observer rats. Furthermore, hippocampal levels of brain-derived neurotrophic factor (BDNF) decreased in both demonstrator and observer rats, whereas rimonabant administration resulted in an increase in BDNF levels in the hippocampus, in contrast to WIN. These results suggest that the CB1R may be intricately involved in prosocial behavior and emotional contagion, potentially through the modulation of BDNF levels in the hippocampus.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"863 ","pages":"Article 138299"},"PeriodicalIF":2.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Masitinib attenuates neuropathological changes in acrolein-induced sAD mouse model via NF-κB/NLRP3/Caspase-1 signaling pathway 马西替尼通过NF-κB/NLRP3/Caspase-1信号通路减弱丙烯醛诱导的sAD小鼠模型的神经病理改变。

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-06-10 DOI: 10.1016/j.neulet.2025.138300

Kang Jia , Qianhui Shen , Zhixian Zhang , Yuan Liu , Yanping Chen , Chao Ding , Shisong Wang , Cailv Wei , Yu Ren , Zhi Liang , Rongbiao Pi , Sigui Zhou

{"title":"Masitinib attenuates neuropathological changes in acrolein-induced sAD mouse model via NF-κB/NLRP3/Caspase-1 signaling pathway","authors":"Kang Jia , Qianhui Shen , Zhixian Zhang , Yuan Liu , Yanping Chen , Chao Ding , Shisong Wang , Cailv Wei , Yu Ren , Zhi Liang , Rongbiao Pi , Sigui Zhou","doi":"10.1016/j.neulet.2025.138300","DOIUrl":"10.1016/j.neulet.2025.138300","url":null,"abstract":"<div><div>Alzheimer’s Disease (AD) is a global health crisis, with sporadic AD (sAD) accounting for more than 95 % of all cases. The lack of effective disease-modifying therapies for sAD, driven by its complex pathogenesis involving genetic, environmental, and lifestyle factors, underscores the urgent need for novel treatments. Masitinib, an oral tyrosine kinase inhibitor originally developed for cancer treatment, has shown potential to regulate mast cells and neuroinflammation, making it a promising candidate against AD. In this study, we investigated the therapeutic effects of masitinib (60 mg/kg/day) in acrolein-induced sAD mouse model. A comprehensive series of behavioral tests, including the buried food pellet tests, Morris water maze, Y-maze, open field, and elevated plus maze, along with Western blot, immunofluorescence and Golgi-Cox staining were used to evaluate pathological changes. The results showed that masitinib significantly improved acrolein-induced olfactory deficits, cognitive dysfunction, particularly in learning and memory, and anxiety-like behaviors. Additionally, masitinib not only reduced p-Tau levels, increased PSD95 expression and restored dendritic spine density, but also suppressed neuroinflammation by inhibiting the NF-κB/NLRP3/caspase-1 inflammatory pathway and microglial activation. These findings demonstrate that masitinib, for the first time, attenuates sAD pathology through dual mechanisms of cognitive enhancement and neuroprotection. Our study provides strong preclinical evidence to support further clinical development of masitinib as a disease-modifying therapy for sAD.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"862 ","pages":"Article 138300"},"PeriodicalIF":2.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-amylose diet ameliorates LPS-induced cognitive impairment and depression-like phenotype 高直链淀粉饮食改善lps诱导的认知障碍和抑郁样表型。

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-06-09 DOI: 10.1016/j.neulet.2025.138295

Kohei Takura , Ran Wei , Rina Takayanagi , Yasumitsu Sakai , Masahira Hattori , Toshio Ohshima

{"title":"High-amylose diet ameliorates LPS-induced cognitive impairment and depression-like phenotype","authors":"Kohei Takura , Ran Wei , Rina Takayanagi , Yasumitsu Sakai , Masahira Hattori , Toshio Ohshima","doi":"10.1016/j.neulet.2025.138295","DOIUrl":"10.1016/j.neulet.2025.138295","url":null,"abstract":"<div><div>Neuroinflammation is accompanied by the activation of glial cells, such as microglia and astrocytes. The cytokines released by these glial cells affect neurons, causing their dysfunction and eventually leading to cell death. Neuroinflammation has been suggested to cause cognitive function decline as well as psychiatric disorders, such as major depressive disorders (MDD). In recent years, from the perspective of the gut-brain axis, a prebiotic approach has been considered to improve neuroinflammation. The ingestion of resistant starch has been reported to increase the number of short-chain fatty acid (SCFA)-producing bacteria, and SCFA may suppress neuroinflammation through the gut-brain relationship in both humans and rodents.</div><div>It is reported that diets rich in amylose, a type of resistant starch, lead to an increase in SCFA levels in the feces of mice. Based on these findings, we hypothesized that a high-amylose diet can ameliorate cognitive impairment and depression-like behaviors driven by neuroinflammation. In the present study, we employed lipopolysaccharides (LPS) to induce neuroinflammation in mice. A fear conditioning test showed that this prebiotic method suppressed the decline of associative learning caused by LPS. In addition, tail suspension and forced swim tests showed the ameliorating effect of this prebiotic method on LPS-induced depression-like behaviors. These results suggest that resistant starch has a prebiotic effect, improving cognitive function decline and depression-like symptoms caused by LPS.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"862 ","pages":"Article 138295"},"PeriodicalIF":2.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of the N-terminal region of Crtac1B/LOTUS, an endogenous Nogo receptor-1 antagonist, required for secretion and soluble function 内源性Nogo受体-1拮抗剂Crtac1B/LOTUS的n端区域特征，这是分泌和可溶性功能所必需的

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-06-08 DOI: 10.1016/j.neulet.2025.138284

Yutaka Kawakami , Haruna Tezuka , Hirokazu Takaya , Junpei Matsubayashi , Kohtaro Takei

{"title":"Characterization of the N-terminal region of Crtac1B/LOTUS, an endogenous Nogo receptor-1 antagonist, required for secretion and soluble function","authors":"Yutaka Kawakami , Haruna Tezuka , Hirokazu Takaya , Junpei Matsubayashi , Kohtaro Takei","doi":"10.1016/j.neulet.2025.138284","DOIUrl":"10.1016/j.neulet.2025.138284","url":null,"abstract":"<div><div>Lateral olfactory tract usher substance (LOTUS), also known as cartilage acidic protein-1B (Crtac1B), is a potent endogenous antagonist of Nogo receptor type-1 (NgR1). LOTUS exists in both membrane-bound (m-LOTUS) and soluble (s-LOTUS) forms. m-LOTUS inhibits NgR1 by binding to its C-terminal domain (UA-EC domain), thereby blocking ligand interactions, whereas s-LOTUS disrupts NgR1 signaling by interfering with its interaction with the p75 co-receptor. However, the molecular characteristics of s-LOTUS, including the functional domains required for secretion and NgR1 binding, remain unclear.</div><div>In this study, we identified the N-terminal 35Met-532Pro region as essential for s-LOTUS secretion. While N-type glycosylation patterns remained unchanged, differences in intracellular localization with the Golgi apparatus were observed between secretory and non-secretory forms. The non-secretory form exhibited higher aggregation and ubiquitination levels. Functionally, the soluble 35Met-532Pro fragment bound to both NgR1 and p75, disrupting the NgR1-p75 complex. In contrast, the UA-EC domain, corresponding to the functional domain of m-LOTUS, bound only to NgR1 and did not interfere with p75 interaction.</div><div>A growth cone collapse assay using cultured olfactory bulb neurons from <em>lotus</em>-deficient embryonic mice demonstrated that exogenous 35Met-532Pro, but not UA-EC, inhibited Nogo66-induced growth cone collapse. These findings indicate that the N-terminal 35Met-532Pro region of s-LOTUS functions as its active domain, antagonizing NgR1 signaling through dual binding to NgR1 and p75. In contrast, the UA-EC domain lacks this antagonistic property, highlighting the distinct functional domains and mechanisms of action between s-LOTUS and m-LOTUS.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"862 ","pages":"Article 138284"},"PeriodicalIF":2.5,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Increasing indoxyl sulfate induces iNOS expression via aryl hydrocarbon receptor leading to microglia hyperactivation in the prefrontal cortex of autism-like offspring rats 增加硫酸吲哚酚通过芳烃受体诱导iNOS表达，导致自闭症样子代大鼠前额皮质小胶质细胞过度活化。

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-06-07 DOI: 10.1016/j.neulet.2025.138298

Yuan Miao , Ruifang Luo , Fang Lin , Bei Tong , Junyan Yan , Ting Yang , Zhujun Sun , Tingyu Li , Lu Xiao , Jie Chen

{"title":"Increasing indoxyl sulfate induces iNOS expression via aryl hydrocarbon receptor leading to microglia hyperactivation in the prefrontal cortex of autism-like offspring rats","authors":"Yuan Miao , Ruifang Luo , Fang Lin , Bei Tong , Junyan Yan , Ting Yang , Zhujun Sun , Tingyu Li , Lu Xiao , Jie Chen","doi":"10.1016/j.neulet.2025.138298","DOIUrl":"10.1016/j.neulet.2025.138298","url":null,"abstract":"<div><div>The abnormal indole metabolism is associated with the progression of Autism Spectrum Disorder (ASD). Indoxyl sulfate (IS), one of the active products of indole metabolism, still has an unknown role in ASD progression. This study investigates the role of IS/Aryl hydrocarbon receptor (AhR)/iNOS pathway in microglial activation in the prefrontal cortex (PFC) of ASD-like rats. Prenatal LPS-exposed induced autism-like behaviors offspring rats, concomitant with increased IS levels in the PFC. The levels of nuclear-AhR, IBA1, CD16 and iNOS proteins expression were increased in the PFC of LPS-exposed rats, whereas ARG1 protein expression level decreased, indicates microglia hyperactivation coupled with altered microglia morphology. ELISA analysis and further measure of synapses changes showed significantly increased inflammatory factors (TNF-α and IL-1β) and synaptic alterations. <em>In vitro</em> experiments demonstrated that IS treatment significantly upregulated the expression level of nuclear-AhR, enhanced microglia marker (IBA1, CD16 and iNOS) proteins and pro-inflammation factors levels (TNF-α and IL-1β), while concurrently reducing ARG1 protein expression and IL-10 levels in BV2 microglial cells. Moreover, the IS treatment significantly enhanced AhR enrichment in <em>iNOS</em> promoter region by chromatin immunoprecipitation and dual luciferase reporter assays, thereby significantly elevating the iNOS expression. However, the AhR-specific antagonist CH-223191 could block this activation and reverse the above proteins and inflammation factors changes. In a word, increased IS levels in the PFC of ASD-like offspring rats activate the AhR/iNOS pathway, driving microglial hyperresponsiveness and contributing to the development of ASD disease.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"862 ","pages":"Article 138298"},"PeriodicalIF":2.5,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0