Neurochemistry international最新文献_第5页

Acute ketamine enhances social behavior and dendritic plasticity in the amygdala by increasing BDNF, GAP43, and TRKB presence following excitotoxic neonatal ibotenic acid lesion 急性氯胺酮通过增加BDNF、GAP43和TRKB的存在，增强兴奋性新生儿伊博滕酸损伤后杏仁核的社交行为和树突可塑性。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-07-01 DOI: 10.1016/j.neuint.2025.106016

Nestor I. Martínez-Torres , Jhonathan Cárdenas-Bedoya , Blanca Miriam Torres-Mendoza

{"title":"Acute ketamine enhances social behavior and dendritic plasticity in the amygdala by increasing BDNF, GAP43, and TRKB presence following excitotoxic neonatal ibotenic acid lesion","authors":"Nestor I. Martínez-Torres , Jhonathan Cárdenas-Bedoya , Blanca Miriam Torres-Mendoza","doi":"10.1016/j.neuint.2025.106016","DOIUrl":"10.1016/j.neuint.2025.106016","url":null,"abstract":"<div><div>Schizophrenia is a highly disabling psychopathology that is a significant burden on public health systems and is characterized by both positive and negative symptoms. One of these negative symptoms is social isolation, which responds poorly to available treatments. Ketamine (KET) has been shown to enhance social behavior in various preclinical models, accompanied by neurobiological changes. In this study, we used a preclinical model of schizophrenia involving neonatal ventral hippocampal (NVHL) bilateral lesions induced by excitotoxicity with ibotenic acid (IA) at postnatal day 7 (PD). Thirty male <em>Sprague-Dawley</em> rats, aged 7 PD, were assigned to one of the following groups: Intact, Sham, Intact + KET, IA + Saline, and IA + KET, with n = 6 per group. Rats in the Sham, IA + Saline, and IA + KET groups underwent stereotaxic surgery and were administered with either 0.3 % saline or IA at 7 PD. At 35 PD, the rats received either saline or ketamine (15 mg/kg) and were assessed using the three-chamber social test. A Golgi-modified technique was then employed to evaluate neuronal changes in the amygdala with Sholl analysis. Also, immunohistochemistry was conducted to measure brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TRKB), and growth-associated protein 43 (GAP43). Acute KET treatment rescued social behavior, increased dendritic tree complexity, and elevated BDNF, TRKB, and GAP43 protein presence. Our results suggest that acute sub-anesthetic administration of KET may help alleviate social isolation symptoms. This dose could provide a window of opportunity to encourage individuals with schizophrenia to initiate and continue their treatment.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"188 ","pages":"Article 106016"},"PeriodicalIF":4.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558720","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

Thiamet-G ameliorates Parkinson's disease-associated cognitive impairment via increasing O-GlcNAcylation of STING in the microglia Thiamet-G通过增加小胶质细胞中STING的o - glcn酰化来改善帕金森病相关的认知障碍

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-06-26 DOI: 10.1016/j.neuint.2025.106014

Shanshan Zhu , Nan Wang , Shuyang Chen , Ju Zou , Sijie Tan

{"title":"Thiamet-G ameliorates Parkinson's disease-associated cognitive impairment via increasing O-GlcNAcylation of STING in the microglia","authors":"Shanshan Zhu , Nan Wang , Shuyang Chen , Ju Zou , Sijie Tan","doi":"10.1016/j.neuint.2025.106014","DOIUrl":"10.1016/j.neuint.2025.106014","url":null,"abstract":"<div><div>Microglia activation contributed to the development of Parkinson's disease (PD)-associated cognitive impairment and targeting microglia may be a promising strategy for improving the cognitive function in PD. O-GlcNAclytion is a novel protein post-translational modification with cognitive enhancing effects. This study aimed to investigate the effects of Thiamet-G (TMG), an O-GlcNAcase inhibitor that can increase the intracellular O-GlcNAclytion levels, on PD-associated cognitive impairment and the mechanism related to microglia activation. A PD mouse model was established using rotenone (ROT) and the cognitive functions of these mice were investigated by behavioral tests. The anti-inflammatory effects of TMG were tested in the BV2 microglia cells. TMG treatment significantly improved the cognitive function in the ROT-induced PD mouse model as evidenced by the Y-maze test and objective recognition test. Histological studies showed that TMG decreased the reactive microglia via increasing the total protein O-GlcNAclytion levels in the hippocampus of the PD mice. In the in vitro studies, TMG inhibited ROT-induced inflammation via decreasing the pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6 in BV2 microglia cells. Bioinformatic analysis revealed that STING, a core protein in the innate immunity regulation, might be a novel target of O-GlcNAclytion. The <strong>i</strong>mmunoprecipitation experiments further confirmed that TMG inhibited STING phosphorylation via increasing O-GlcNAcylation. Taken together, <span>TMG</span> might ameliorate PD-associated cognitive impairment via increasing O-GlcNAcylation of STING in microglia, which provided evidence supporting that inhibiting the inflammatory response of microglia by elevating the O-GlcNAclytion levels might be an effective strategy for improving the cognitive function in PD.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"188 ","pages":"Article 106014"},"PeriodicalIF":4.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502576","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

Anti-inflammatory and analgesic effects of marine-derived antimicrobial peptide tilapia piscidin 3(TP3) in alleviating chronic constriction injury-induced neuropathic pain in rats 海洋来源抗菌肽Piscidin 3（TP3）对大鼠慢性收缩性损伤神经性疼痛的抗炎镇痛作用

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-06-20 DOI: 10.1016/j.neuint.2025.106013

Jui-Kang Tsai , Zong-Sheng Wu , San-Nan Yang , Shi-Ying Huang , Hui-Lu Chen , Wei-Ning Teng , Fu-Wei Su , Wu-Fu Chen , Zhi-Hong Wen , Chun-Sung Sung

{"title":"Anti-inflammatory and analgesic effects of marine-derived antimicrobial peptide tilapia piscidin 3(TP3) in alleviating chronic constriction injury-induced neuropathic pain in rats","authors":"Jui-Kang Tsai , Zong-Sheng Wu , San-Nan Yang , Shi-Ying Huang , Hui-Lu Chen , Wei-Ning Teng , Fu-Wei Su , Wu-Fu Chen , Zhi-Hong Wen , Chun-Sung Sung","doi":"10.1016/j.neuint.2025.106013","DOIUrl":"10.1016/j.neuint.2025.106013","url":null,"abstract":"<div><div>Neuropathic pain has multiple etiologies, and many patients remain inadequately treated. The cyclic adenosine monophosphate (cAMP) signaling pathway plays a critical role in inflammatory responses, particularly through the upregulation of proinflammatory cytokines. This study aimed to investigate the anti-inflammatory and analgesic properties of the marine-derived antimicrobial peptide Tilapia Piscidin 3 (TP3), using a chronic constriction injury (CCI) model to simulate neuropathic pain. In vitro assays showed that TP3 exerted a dose-dependent inhibitory effect on lipopolysaccharide-induced proinflammatory cytokine expression in mouse BV-2 microglia and RAW 264.7 macrophages. Nociceptive behavioral tests revealed that intrathecal (IT) administration of TP3 alleviated CCI-induced mechanical allodynia and thermal hyperalgesia. Immunofluorescence analysis showed that IT TP3 significantly increased phosphodiesterase 4D (PDE4D) levels and decreased the expression of cAMP, brain-derived neurotrophic factor (BDNF), and tumor necrosis factor-α in astrocytes within the dorsal horn of the spinal cord in CCI rats. The antinociceptive effects of TP3 were abolished by the PDE4D inhibitor rolipram, highlighting the role of PDE4D-mediated modulation of the cAMP pathway in producing these effects. These findings suggest that TP3 may be a promising therapeutic agent for treating neuropathic pain by exerting anti-inflammatory and analgesic effects through regulation of the cAMP pathway.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"188 ","pages":"Article 106013"},"PeriodicalIF":4.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367782","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

Pathway-specific regulation of amphetamine-induced conditioned place preference by chemogenetic modulation of basolateral amygdala projections to prelimbic cortex and nucleus accumbens subregions 安非他明诱导的条件位置偏好的通路特异性调控：杏仁核基底外侧向前边缘皮层和伏隔核亚区投射的化学发生调节

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-06-18 DOI: 10.1016/j.neuint.2025.106012

Joonyeup Han , Haeun Rim , Hanbyual Jang , Wen Ting Cai , Wha Young Kim , Jeong-Hoon Kim

{"title":"Pathway-specific regulation of amphetamine-induced conditioned place preference by chemogenetic modulation of basolateral amygdala projections to prelimbic cortex and nucleus accumbens subregions","authors":"Joonyeup Han , Haeun Rim , Hanbyual Jang , Wen Ting Cai , Wha Young Kim , Jeong-Hoon Kim","doi":"10.1016/j.neuint.2025.106012","DOIUrl":"10.1016/j.neuint.2025.106012","url":null,"abstract":"<div><div>Individuals with substance use disorders develop maladaptive associative memories, linking environmental contexts with drug experiences. The basolateral amygdala (BLA), prelimbic cortex (PrL), and nucleus accumbens (NAc) are central components of the neural circuitry underlying these associations. However, it remains unclear how specific BLA outputs differentially regulate the expression of contextual drug memories. Using designer receptors exclusively activated by designer drugs, we selectively modulated neuronal activity with deschloroclozapine as the activating agent during the expression of amphetamine-induced conditioned place preference (CPP) in the BLA pathways to the PrL, NAc core, and NAc shell. Our findings revealed a dissociation between these pathways: the BLA-to-PrL circuit exerted bidirectional control over CPP expression, with inhibition significantly enhancing and activation attenuating drug-context associations. In contrast, BLA-to-NAc core manipulations selectively modulated locomotor aspects of conditioned responses without affecting place preference, while BLA-to-NAc shell manipulations produced no significant effects on CPP expression. These results demonstrate that the BLA has a distinctive pathway-specific roles in the expression of contextual drug memory.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"188 ","pages":"Article 106012"},"PeriodicalIF":4.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322709","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

Differential synaptic inhibition and serotonin 5-HT7 receptor-mediated modulation in identified dorsal horn neurons 鉴定的背角神经元的差异突触抑制和血清素5-HT7受体介导的调节

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-06-18 DOI: 10.1016/j.neuint.2025.106011

Chiara Salio , Francesco Ferrini , Andrea Bighinati , Enza Lacivita , Marcello Leopoldo , Rita Bardoni

{"title":"Differential synaptic inhibition and serotonin 5-HT7 receptor-mediated modulation in identified dorsal horn neurons","authors":"Chiara Salio , Francesco Ferrini , Andrea Bighinati , Enza Lacivita , Marcello Leopoldo , Rita Bardoni","doi":"10.1016/j.neuint.2025.106011","DOIUrl":"10.1016/j.neuint.2025.106011","url":null,"abstract":"<div><div>Serotonergic modulation of pain transmission in the spinal cord involves the activation of multiple receptor types, including 5-HT<sub>7</sub> receptors. Activation of spinal 5-HT<sub>7</sub> receptors appears to have a predominant antinociceptive effect in various animal models. Although the serotonergic modulation of dorsal horn circuits has been extensively investigated, information about the specific effects of serotonergic receptors on identified neuron types remains limited. To address this, we have employed transgenic mice expressing channelrhodopsin-2 (ChR2) in inhibitory neurons, under the control of the vesicular GABA transporter (VGAT) promoter. Postsynaptic inhibitory responses (oIPSCs) induced by optogenetic stimulation of spinal cord slices displayed distinct properties in superficial dorsal horn VGAT+ and VGAT- neurons (inhibitory and putative excitatory neurons, respectively). While oIPSCs recorded from VGAT + neurons showed GABA- and glycine-mediated components of similar amplitudes, oIPSCs from VGAT- neurons were predominantly mediated by glycine. Consistently, immunofluorescence staining for the glycine transporter GlyT2 in mice expressing dTomato in GAD2 neurons revealed that GlyT2+ boutons primarily contact putative excitatory interneurons, which are negative for GAD2. Activation of 5-HT<sub>7</sub> receptors by the agonist LP-211 significantly enhanced both the frequency of spontaneous inhibitory currents and the amplitude of oIPSCs in VGAT- neurons. In minimal optical stimulation experiments, application of LP-211 reduced the number of synaptic failures and increased the quantal content of oIPSCs, indicating presynaptic modulation mediated by 5-HT<sub>7</sub> receptors. Our results suggest that enhanced synaptic inhibition of dorsal horn excitatory interneurons may contribute to the role of 5-HT<sub>7</sub> receptors in suppressing pain transmission at the spinal cord level.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"188 ","pages":"Article 106011"},"PeriodicalIF":4.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331187","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

Antinociceptive and anti-inflammatory effects of dihydroaustrasulfone alcohol in alleviating peripheral neuropathy via Nrf2/HO-1 pathway in rats 二氢奥斯柳酮醇通过Nrf2/HO-1通路减轻大鼠周围神经病变的抗伤性和抗炎作用

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-06-17 DOI: 10.1016/j.neuint.2025.106010

Chun-Sung Sung , Hao-Jung Cheng , San-Nan Yang , Pei-Jyuan Li , Shi-Ying Huang , Wu-Fu Chen , Nan-Fu Chen , Jui-Kang Tsai , Zhi-Hong Wen

{"title":"Antinociceptive and anti-inflammatory effects of dihydroaustrasulfone alcohol in alleviating peripheral neuropathy via Nrf2/HO-1 pathway in rats","authors":"Chun-Sung Sung , Hao-Jung Cheng , San-Nan Yang , Pei-Jyuan Li , Shi-Ying Huang , Wu-Fu Chen , Nan-Fu Chen , Jui-Kang Tsai , Zhi-Hong Wen","doi":"10.1016/j.neuint.2025.106010","DOIUrl":"10.1016/j.neuint.2025.106010","url":null,"abstract":"<div><div>Peripheral neuropathic pain is closely associated with neuroinflammation and oxidative stress accumulation in the spinal cord dorsal horn (SCDH), but effective treatments remain limited. Dihydroaustrasulfone alcohol (WA25), a synthetic precursor of austrasulfone obtained from a Formosan soft coral, has anti-inflammatory and antioxidant properties. However, its potential therapeutic effect on neuropathic pain is yet to be established. This study aimed to elucidate the cellular mechanisms responsible for therapeutic potential of WA25 in rats with neuropathic pain. Neuropathic pain was induced in rats via chronic constriction injury (CCI), and WA25 was intrathecally administered in these rats. To evaluate the analgesic effects of WA25 and the underlying cellular mechanisms, nociceptive behavior assessment and immunofluorescence staining, respectively, were employed. WA25 significantly alleviated CCI-induced nociceptive behavior, neuroinflammation, and oxidative stress accumulation. Further, WA25 enhanced the expression of astrocytic nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the ipsilateral SCDH, suggesting its role in mitigating inflammation and oxidative stress. The co-administration of the HO-1 inhibitor ZnPP abolished the analgesic, anti-inflammatory, and antioxidant effects of WA25. The findings of the study suggest that WA25 effectively attenuates nociceptive sensitization, neuroinflammation, and oxidative stress accumulation in rats via the activation of the Nrf2/HO-1 signaling pathway, highlighting its potential as a therapeutic agent for neuropathic pain management.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"188 ","pages":"Article 106010"},"PeriodicalIF":4.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338649","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

Deferoxamine prevents BBB disruption, neuroinflammation and apoptotic changes in early hours of ischemic reperfusion injury 去铁胺可预防缺血再灌注损伤早期血脑屏障破坏、神经炎症和细胞凋亡改变。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-06-13 DOI: 10.1016/j.neuint.2025.106009

Rajesh Ugale, Sneha Vatte, Punit Girdhar, Dinesh Anandani

{"title":"Deferoxamine prevents BBB disruption, neuroinflammation and apoptotic changes in early hours of ischemic reperfusion injury","authors":"Rajesh Ugale, Sneha Vatte, Punit Girdhar, Dinesh Anandani","doi":"10.1016/j.neuint.2025.106009","DOIUrl":"10.1016/j.neuint.2025.106009","url":null,"abstract":"<div><h3>Background</h3><div>Iron contributes to brain damage in ischemia/reperfusion injury (I/R). Deferoxamine (DFX), an iron chelator, offers neuroprotective action in I/R animal models. However, its underlying mechanism is under investigation. This study aims to investigate effect of DFX on I/R damage led by BBB disruption, neuroinflammation, and apoptosis.</div></div><div><h3>Methods</h3><div>In adult male Wistar rats, cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). Rats were treated with vehicle or DFX at 100, 200, and 300 mg/kg doses intraperitoneally (<em>i.p.</em>) at time intervals 1, 2, and 3 h of I/R injury. The neuroprotective effect of DFX was observed using histological staining and behavioural assessment after 24 h of I/R injury. Blood-brain barrier (BBB) integrity was evaluated by Evans blue staining & MMP9 expression. Anti-inflammatory effect of DFX was observed using immunohistochemical analysis whereas, anti-apoptotic effects via mRNA expressions of CREB, caspase-3, BDNF and Bcl-2.</div></div><div><h3>Results</h3><div>DFX (300 mg/kg) at 1 h of I/R injury ameliorates cerebral infarction, neurological deficits, and beam walk score. Histologically, Hoechst, hematoxylin and eosin (H & E), and cresyl violet stainings showed reduced neuronal death in DFX treated rats. It mitigates BBB disruption as observed with Evans blue staining. Additionally, DFX reduced MMP-9 expression indicative of reduced BBB disruption and improved inflammatory changes (CD86 and CD206). Besides, it inhibits mRNA expression of cleaved caspase-3 and improved expression of BDNF and Bcl-2.</div></div><div><h3>Conclusions</h3><div>Our findings, demonstrate that DFX prevents I/R brain damage in early hour (1 h) of I/R injury by reducing BBB disruption, inflammation, and apoptosis. DFX may exhibit potential to act as adjuvant in management of acute ischemic stroke.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"188 ","pages":"Article 106009"},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300917","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

Epitranscriptomic shifts in M6A RNA methylation influencing transcriptional dynamics in the prefrontal cortex of chronic restraint stress rats 慢性限制性应激大鼠前额皮质M6A RNA甲基化的表观转录组改变影响转录动力学。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-06-13 DOI: 10.1016/j.neuint.2025.106008

Yu Funahashi , Bhaskar Roy , Kevin Prall , Yogesh Dwivedi

{"title":"Epitranscriptomic shifts in M6A RNA methylation influencing transcriptional dynamics in the prefrontal cortex of chronic restraint stress rats","authors":"Yu Funahashi , Bhaskar Roy , Kevin Prall , Yogesh Dwivedi","doi":"10.1016/j.neuint.2025.106008","DOIUrl":"10.1016/j.neuint.2025.106008","url":null,"abstract":"<div><div>Chronic restraint stress (CRS) is a widely used model for investigating stress-induced molecular and neuronal changes. In this study, we examined transcriptome-wide m6A methylation in the prefrontal cortex of CRS rats to understand the molecular impact of stress. Elevated plasma corticosterone levels confirmed the physiological stress response in CRS rats. MeRIP-seq analysis identified 21,669 differentially methylated transcripts, with a predominant hypermethylation pattern (4,301 transcripts) compared to a smaller subset of hypomethylated transcripts (79). Chromosomal distribution revealed widespread hypermethylation across multiple chromosomes, with notable peaks on chromosomes 1, 3, and 10. Gene expression profiling indicated differential regulation of 1,424 genes, with 847 upregulated and 577 downregulated in CRS rats. Integration of m6A methylation and gene expression data revealed an inverse correlation, where hypermethylated transcripts were downregulated, suggesting a role for m6A in transcript stability and turnover. Functional analysis of hypermethylated transcripts highlighted enrichment in key neuronal processes, including synaptic plasticity, neurotransmitter signaling, and chromatin remodeling. Additionally, the 3′UTR of coding transcripts exhibited enriched m6A methylation marks, suggesting a regulatory role in mRNA stability and translation efficiency. RNA level expression analysis revealed significant downregulation of key m6A methylation-related enzymes (METTL3, METTL14, and ALKBH5), further supporting m6A dysregulation under CRS. Pathway analysis underscored the involvement of differentially methylated transcripts in RNA metabolism, chromatin remodeling, and neurobiological pathways linked to stress-related psychiatric disorders. Altogether, the study provides insight into the epitranscriptomic mechanisms underlying stress responses and their implications in neuropsychiatric disorders such as major depression.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"188 ","pages":"Article 106008"},"PeriodicalIF":4.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300918","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

DNA methylation and hydroxymethylation dynamics in the aging brain and its impact on ischemic stroke 衰老脑中的DNA甲基化和羟甲基化动力学及其对缺血性脑卒中的影响

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-06-11 DOI: 10.1016/j.neuint.2025.106007

Vijay Arruri , Pallavi Joshi , Raghu Vemuganti

引用次数: 0

Neurochemical in vivo microdialysis and postmortem tissue analysis of amygdala endocannabinoid levels after MAGL- and FAAH-inhibition in rodents MAGL-和faah抑制后啮齿动物杏仁核内源性大麻素水平的神经化学体内微透析和死后组织分析。

IF 4.4 3区医学

Neurochemistry international Pub Date : 2025-06-08 DOI: 10.1016/j.neuint.2025.106006

Mariette S. Heins , Marc D. Ferger , Patrizia Voehringer , Thomas I.F.H. Cremers , Boris Ferger

{"title":"Neurochemical in vivo microdialysis and postmortem tissue analysis of amygdala endocannabinoid levels after MAGL- and FAAH-inhibition in rodents","authors":"Mariette S. Heins , Marc D. Ferger , Patrizia Voehringer , Thomas I.F.H. Cremers , Boris Ferger","doi":"10.1016/j.neuint.2025.106006","DOIUrl":"10.1016/j.neuint.2025.106006","url":null,"abstract":"<div><div>This study is the first to investigate the target modulation of the MAGL inhibitor elcubragistat (ABX-1431; Lu-AG06466) and the FAAH inhibitor JNJ-42165279 in the amygdala, a brain region involved in stress-induced psychiatric disorders.</div><div>We aimed to assess dynamic changes in the endocannabinoid ligands 2-arachidonoylglycerol (2-AG) and anandamide (AEA) following pharmacological inhibition of MAGL and FAAH, enzymes regulating their metabolism.</div><div>Freely moving rats received oral doses of elcubragistat or JNJ-42165279. Microdialysis probes in the basolateral amygdala and nucleus accumbens measured extracellular 2-AG and AEA levels over 240 min using LC-MS/MS. A supplementary mouse study analyzed postmortem endocannabinoid levels in the basolateral amygdala.</div><div>MAGL inhibition by elcubragistat selectively increased extracellular and tissue 2-AG levels in the basolateral amygdala in a dose-related manner without affecting AEA. Conversely, FAAH inhibition by JNJ-42165279 selectively elevated AEA levels without altering 2-AG. Highest endocannabinoid concentration in basolateral amygdala tissue was between 2 and 4 h after MAGL or FAAH inhibition.</div><div><em>In vivo</em> microdialysis is a sensitive method to study target modulation of both MAGL and FAAH inhibitors in the amygdala of freely moving rats. The results of the microdialysis study are in general agreement with postmortem tissue analysis of both 2-AG and AEA and suitable to support the preclinical drug discovery process in concert with disease related animal models.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"188 ","pages":"Article 106006"},"PeriodicalIF":4.4,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264998","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