Neurochemistry international最新文献

{"title":"Differences in presynaptic hippocampal GABAergic terminals at the early stage of life in female and male mice: effect of an acute early inflammatory challenge","authors":"Cristina Benatti ,&nbsp;Alessandra Roggeri ,&nbsp;Ylenia Toscano ,&nbsp;Veronica Torre ,&nbsp;Nicoletta Brunello ,&nbsp;Fabio Tascedda ,&nbsp;Johanna Maria Catharina Blom ,&nbsp;Anna Pittaluga","doi":"10.1016/j.neuint.2025.106062","DOIUrl":"10.1016/j.neuint.2025.106062","url":null,"abstract":"<div><div>GABA dictates the efficiency of synaptic connection, influencing its developmental complexity, but its role is tuned by developmental sex differences which affect the efficiency of its innervation. We investigated the efficiency of mechanisms of GABA storage and exocytosis in hippocampal terminals of male and female mice during the juvenile period (PND21), adolescence (PND36) or adulthood (PND90). The expression of mRNA encoding for the presynaptic GABA transporter type 1, (GAT1) and the vesicular GABA transporter (VGAT1) was analysed. A significant scaling-down in the GAT1 mRNA levels (SLC6A1) was detected at PND21 in both sexes until adulthood, while the SLC32A1-VGAT mRNA level was conserved. We also analysed the density of GAT1 and VGAT proteins. Western blot analysis unveiled the presence of a monomeric and an oligomeric form of GAT1. The density of the monomeric form was conserved at the different stages of development in both sexes. Differently, the oligomeric assembly was significantly overexpressed in hippocampal synaptosomal lysates from PND21 male and female mice, but recovered at PND36. VGAT density was largely conserved in PND21 and PND36 male hippocampal synaptosomal lysates when compared to adult particles, but significantly lower in PND21 female particles. Notably, these changes are consistent and support the altered vesicular storage of newly taken-up [³H]GABA detected in PND21 male and female hippocampal synaptosomes as well as the different responsiveness of GABAergic male and female synaptosomes to increasing depolarizing stimuli (12, 20 and 30 mM KCl-enriched solutions) measured as efficiency of the [³H]GABA exocytosis. Interstingly, an acute LPS treatment affects the efficiency of GABA exocytosis at PND36 in a sex-dependent manner. These results add new knowledge on the role of GABA as effector of central inhibitory plasticity at the early stage of development and its relevance in dimorphic adaptation in physio pathological conditions.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106062"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237879","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":"Clinically relevant infraorbital nerve deflation and chronic constriction injury models of trigeminal neuralgia display unifying mechanisms","authors":"Srilakshmi Satti ,&nbsp;Shwetali Ramteke ,&nbsp;Sowmya Chaganti ,&nbsp;Hara Prasad Padhy ,&nbsp;Gananadhamu Samanthula ,&nbsp;Manoj P. Dandekar","doi":"10.1016/j.neuint.2025.106052","DOIUrl":"10.1016/j.neuint.2025.106052","url":null,"abstract":"<div><h3>Background</h3><div>Trigeminal neuralgia is a debilitating pain condition that occurs due to the deflation of trigeminal nerve. Herein, we developed clinically relevant trigeminal neuralgia model using a distal infraorbital trigeminal nerve chronic deflation injury (dIoN CDI) in male and female rats. The results were compared with an existing distal infraorbital nerve chronic constriction injury (dIoN CCI) model.</div></div><div><h3>Methods</h3><div>Pain-related assessments were conducted by von-Frey filaments, orofacial-pain assessment device (OPAD), grooming time and rat-grimace scale (RGS). Anxiodepressive-phenotypes were assessed by elevated-plus maze test (EPM), sucrose-preference test (SPT), forced-swim test (FST), splash test. Brain, trigeminal nerve, faeces and blood samples were collected for molecular analysis.</div></div><div><h3>Results</h3><div>Rats subjected to dIoN CCI and dIoN CDI surgery displayed a decrease in von-Frey threshold and lick number in OPAD. The grooming time and RGS also indicated development of pain. A significant decrease in sucrose consumption in male rats and less exploration of open arms in EPM test by female rats, indicated the development of chronic pain-generated anxiodepressive behaviors. In biomarkers analysis, dIoN CCI and dIoN CDI groups showed elevated expression of calcitonin gene-related peptide and substance P in spinal trigeminal nucleus and/or ganglia. These groups also showed enhanced levels of dopamine, acetylcholine, 5-HT, and corticosterone and decreased concentration of GABA and noradrenaline in frontal and somatosensory cortices, brainstem and plasma. We also noted altered levels of sex hormones, fecal short-chain fatty acids, and occludin expression in the colon.</div></div><div><h3>Conclusion</h3><div>These results indicate that both trigeminal neuralgia models display unifying principles in male and female rats.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106052"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051527","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":"Developmental neuroplasticity enables recovery from anesthetic-induced synaptic perturbations in the immature brain","authors":"Lixi Chen ,&nbsp;Zhiduo Zhang ,&nbsp;Shana Yang ,&nbsp;Yun Tang ,&nbsp;Xuanhe Wang ,&nbsp;Wenfu Li ,&nbsp;Lin Yang ,&nbsp;Chenyi Guo ,&nbsp;Shunchang Fang ,&nbsp;Wenhui Xiao ,&nbsp;Minbiao Yan ,&nbsp;Yonglin Li ,&nbsp;Taixuan Peng ,&nbsp;Boxing Li ,&nbsp;Xiao Min Zhang ,&nbsp;Lianyan Huang","doi":"10.1016/j.neuint.2025.106051","DOIUrl":"10.1016/j.neuint.2025.106051","url":null,"abstract":"<div><div>General anesthetics are essential in pediatric medicine, yet concerns persist regarding their potential neurotoxic effects on the developing brain. Whether transient synaptic disruptions caused by anesthesia lead to long-term deficits or are mitigated by endogenous plasticity remains unresolved. Here, we use longitudinal <em>in vivo</em> two-photon imaging in awake mice to investigate the structural and functional consequences of a single, clinically relevant exposure to sevoflurane at postnatal day 20. We find that sevoflurane induces transient behavioral hyperactivity and suppresses filopodia elimination. Remarkably, these effects are fully reversed within 24 h. Across a 10 days follow-up, we observe no persistent alterations in synaptogenesis, neuronal activity, motor learning, or anxiety-like behavior. Electrophysiological recording and calcium imaging further confirm the restoration of normal firing and synaptic transmission in layer 5 pyramidal neurons. These findings reveal a dual-phase recovery mechanism—acute plasticity followed by chronic convergence, highlighting the developing brain's intrinsic resilience to transient anesthetic insults. Our study redefines sevoflurane not as a source of irreversible neurotoxicity but as a temporary challenge that can be effectively buffered by developmental neuroplasticity, offering important reassurance for its continued use in pediatric anesthesia.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106051"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032545","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":"In vitro pharmacological activity of twenty-eight synthetic cannabinoid receptor agonists at the type 1 and 2 cannabinoid receptors","authors":"Gabrielle Mercier ,&nbsp;Kawthar A. Mohamed ,&nbsp;Ayat Zagzoog ,&nbsp;Laura Cropper ,&nbsp;Brendan Ritchie ,&nbsp;Zhiyun Jin ,&nbsp;Mikin Patel ,&nbsp;Robert B. Laprairie","doi":"10.1016/j.neuint.2025.106039","DOIUrl":"10.1016/j.neuint.2025.106039","url":null,"abstract":"<div><div>Synthetic cannabinoid receptor agonists (SCRAs) are a class of novel psychoactive substances whose prevalence in illegal markets continues to grow. Δ⁹-tetrahydrocannabinol (THC) is the primary intoxicating compound present in cannabis and is well-known to behave as a partial agonist at both the type 1 and 2 cannabinoid receptors (CB1R, CB2R). Unlike THC, the SCRAs characterized to date generally behave as CB1R and/or CB2R full agonists. The high potency and full agonism of these ligands are thought to drive the toxicity of SCRAs, including psychoses, emesis, and tachycardia. In this study, twenty-eight compounds (including the reference ligands CP55,940 and THC) were evaluated for binding affinity, Gi protein-dependent inhibition of cAMP, and βarrestin2 recruitment in Chinese hamster ovary (CHO–K1) cells stably expressing either receptor. Radioligand binding results demonstrate a general lack of selectivity between cannabinoid receptor subtypes. In signaling assays, most compounds displayed the anticipated full agonism with low nanomolar potency characteristic of SCRAs. Many compounds displayed bias for the inhibition of cAMP over the recruitment of βarrestin2, and this was especially true at CB2R, where several compounds were inactive in the βarrestin2 recruitment assay. However, no clear structure-activity relationship emerged among the tested SCRAs that could account for their selectivity, potency, efficacy, or bias, although potential patterns are discussed herein. Overall, our data support growing evidence that the cannabinoid receptors accommodate a diverse range of ligands, and that compound function may be dictated by factors that are not yet well characterized, such as binding kinetics.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106039"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917409","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":"Targeting ferroptosis by electroacupuncture offers a therapeutic regimen for brain injury after ischemic stroke","authors":"Wenjing Li,&nbsp;Qiang Li","doi":"10.1016/j.neuint.2025.106038","DOIUrl":"10.1016/j.neuint.2025.106038","url":null,"abstract":"<div><div>Ischemic stroke (IS), the most prevalent form of stroke, remains a significant healthcare challenge and imposes a considerable burden on affected individuals. Ferroptosis, a form of regulated cell death (RCD) characterized by iron overload -induced lipid peroxidation, was identified as a contributor to induce cell death following brain injury after ischemic stroke. Targeting ferroptosis is a novel therapy regimen for IS. And seeking novel therapy is unmet need for IS. Electroacupuncture (EA) has been revealed to have neuroprotective effect against IS and recommended to treat IS by World Health Organization (WHO) for years, but the specific mechanism underlying EA-mediated neuroprotection is still elusive. Emerging evidences have shown that EA alleviates brain injury after ischemic stroke by inhibiting ferroptosis; however, the mechanism by which EA suppresses ferroptosis against IS has not been sufficiently clarified. In this review, we first summarizes the core molecular mechanism of ferroptosis, with an focus on interpret how ferroptosis leads to the genesis of brain injury after ischemic stroke and the novel regulation of ferroptosis during the brain injury after ischemic stroke. We then highlights our emphasize on the emerging evidences that have revealed EA inhibit ferroptosis and review their pharmacological mechanisms against brain injury after ischemic stroke. This review highlights EA as a novel therapeutic regimen for ischemic stroke by suppressing ferroptosis, synthesizing mechanistic insights into iron-dependent lipid peroxidation pathways, evaluating emerging experimental evidence of EA's neuroprotection, and proposing targeted clinical strategies to mitigate post-stroke brain injury.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106038"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896185","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":"Multi-omics reveals changes in astrocyte fatty acid metabolism during early stages of Alzheimer's disease","authors":"Jie Zhong ,&nbsp;Manhui Li ,&nbsp;Ziwei Dai ,&nbsp;Jun Wan","doi":"10.1016/j.neuint.2025.106049","DOIUrl":"10.1016/j.neuint.2025.106049","url":null,"abstract":"<div><h3>Background</h3><div>Although astrocytes are known to contribute to Alzheimer's disease (AD) progression, their dynamic molecular alterations remain poorly characterized, particularly in early stages of the disease.</div></div><div><h3>Methods</h3><div>We performed multi-omics profiling (transcriptomics, proteomics, spatial metabolomics) of astrocytes from APP/PS1 and WT mice to characterize dynamic changes during AD progression. To assess similar changes in early human AD, we analyzed single-nucleus RNA sequencing data from human samples.</div></div><div><h3>Results</h3><div>Transcriptomic analysis of astrocytes from APP/PS1 and WT mice at five time points (2, 4, 6, 9, and 12 months of age) showed notable gene expression differences at 6 months, with reduced activity in fatty acid metabolism pathways (e.g., PPAR signaling, biosynthesis of unsaturated fatty acids). An astrocyte-specific metabolic model confirmed these disruptions. Proteomic analysis corroborated this by showing decreased activity in pathways like butanoate metabolism and PPAR signaling. Spatial metabolomics of brain slices from APP/PS1 and WT mice highlighted fatty acid enrichment in the hippocampus and cortex, alongside differential metabolites specific to the AD mouse model. Single-cell RNA sequencing analysis of human brain samples further showed fatty acid metabolism abnormalities in astrocytes from early AD cases versus controls, emphasizing its role in AD progression.</div></div><div><h3>Conclusion</h3><div>Our study identified abnormal fatty acid metabolism as an early feature of astrocytes in AD, suggesting an association between dysregulated fatty acid metabolism and disease progression.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106049"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937974","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":"Further characterisation of the intrastriatal 6-OHDA Parkinson's disease model with non-motor symptom replication and widespread catecholamine dysfunction in male mice","authors":"Alisha Braun ,&nbsp;Jessica Racz ,&nbsp;Sanjay Garg ,&nbsp;Larisa Bobrovskaya","doi":"10.1016/j.neuint.2025.106054","DOIUrl":"10.1016/j.neuint.2025.106054","url":null,"abstract":"<div><div>The 6-OHDA mouse model of Parkinson's disease is not well characterised, with variable dosages, injection sites and timeframes. This study further characterised the unilateral intrastriatal 8 μg 6-OHDA mouse model using a four-week protocol, with replication of motor and some non-motor symptoms in male mice. Non-motor symptom replication included cognitive impairment and gastrointestinal dysfunction. Olfactory dysfunction and anxiety-like behaviour were unable to be replicated in this study. Parkinson's disease pathology, particularly non-motor pathology, was also investigated in this study which found the intrastriatal 6-OHDA lesion caused widespread catecholamine dysfunction outside of the nigrostriatal pathway, including the mesocortical and mesolimbic pathway. Proteins involved in neuroinflammation (GFAP), oxidative stress defence (SOD2) and synaptic proteins (SNAP25) were altered, as seen in Parkinson's disease pathology, in the brains of the 6-OHDA lesioned mice.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106054"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102616","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":"SPP1 expression after spinal cord compression injury and its effects on glial cell activation","authors":"Linkai Lei ,&nbsp;Xinping Wang ,&nbsp;Jijuan Zhao","doi":"10.1016/j.neuint.2025.106063","DOIUrl":"10.1016/j.neuint.2025.106063","url":null,"abstract":"<div><h3>Purpose</h3><div>To study the role and mechanism of SPP1 in spinal cord injury.</div></div><div><h3>Methods</h3><div>We created a rat model of spinal cord compression injury (SCI) and examined the expression of SPP1 in spinal cord tissue using western blotting and immunofluorescence staining. We assessed motor function and pathological repair in SCI rats using the BBB locomotor scale, swimming tests, HE staining, Nissl staining, myelin staining, immunofluorescence, and western blot experiments. Additionally, we examined microglial activation and inflammatory phenotypes to analyze underlying mechanisms. To determine if SPP1's effects are linked to MK2, we used the MK2 inhibitor PF-364402.</div></div><div><h3>Results</h3><div>After spinal cord injury, the expression level of SPP1 exhibited a significant increase, peaking on the third day post-injury. A co-localization relationship was noted with Iba-1-labeled microglia. Reduced SPP1 expression enhanced motor function recovery and aided in spinal cord tissue repair after injury in mice. Low SPP1 expression modulated glial cell inflammation, reducing the iNOS-labeled pro-inflammatory phenotype and increasing the Arg-1-labeled anti-inflammatory phenotype. This modulation subsequently inhibited the activation of microglia. Furthermore, we validated the inhibitory effect of low SPP1 expression on the activation of the MK2 signaling pathway, which was associated with a reduction in the phosphorylation levels of MK2, p38, and NF-κB.</div></div><div><h3>Conclusion</h3><div>This study found that SPP1 was highly expressed in rats with spinal cord injury and was associated with microglial activation and inflammatory phenotype transformation. Low levels of SPP1 promoted neural repair and motor function recovery, which may be related to the MK2 pathway.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106063"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181793","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 potential of mulberry (Morus alba L.) leaf extract against pro-aggregant tau-mediated inflammation and mitochondrial dysfunction","authors":"Te-Hsien Lin ,&nbsp;Pei-Hsuan Tseng ,&nbsp;I-Cheng Chen ,&nbsp;Chung-Yin Lin ,&nbsp;Ming-Chung Lee ,&nbsp;Kuo-Hsuan Chang ,&nbsp;Guey-Jen Lee-Chen ,&nbsp;Chiung-Mei Chen","doi":"10.1016/j.neuint.2025.106042","DOIUrl":"10.1016/j.neuint.2025.106042","url":null,"abstract":"<div><div>In Alzheimer's disease (AD), Tau aggregates trigger microglial activation to release inflammatory factors and cause mitochondrial dysfunction, oxidative stress, and neuronal damage. With abundant potent antioxidants, mulberry (<em>Morus alba</em> L.) leaf extract has the potential to treat diseases associated with neuroinflammation, mitochondrial dysfunction, and oxidative stress. This study examined the neuroprotective effects of a mulberry leaf extract against pro-aggregant Tau-mediated inflammation and mitochondrial dysfunction in SH-SY5Y cells expressing the ΔK280 Tau repeat domain (Tau_RD). His-tagged ΔK280 Tau_RD fibrils prepared from <em>E. coli</em> activated BV-2 microglia, as revealed by their altered morphology, increased nitric oxide production, and elevated ionized calcium binding adaptor molecule 1 (IBA1) and major histocompatibility complex 2 (MHCII) expression. The mulberry leaf extract suppressed the production of pro-inflammatory mediators, including NO, IL-1β, IL-6, and TNF-α, and the expression of NLR family pyrin domain-containing 3 (NLRP3) and caspase-1 (CASP1) in ΔK280 Tau_RD fibril-stimulated BV-2 cells. Application of conditioned media collected from ΔK280 Tau_RD fibril-activated BV-2 cells induced cellular inflammation in ΔK280 Tau_RD-DsRed-expressing SH-SY5Y cells. The mulberry leaf extract protected these cells by suppressing lactate dehydrogenase (LDH) release, caspase-3 activity, NLR family pyrin domain-containing 1 (NLRP1), CASP1, IL-1β, IL-6, TNF-α, and reactive oxygen species as well as by enhancing neurite outgrowth. In addition, mulberry leaf extract increased mitochondrial membrane potential, lowered mitochondrial superoxide levels, and increased superoxide dismutase 2 (SOD2), NAD(P)H quinone dehydrogenase 1 (NQO1), glutamate-cysteine ligase catalytic subunit (GCLC), and nuclear factor erythroid 2-related factor 2 (NRF2) levels in SH-SY5Y cells. In conclusion, mulberry leaf extract displayed neuroprotective effects by exerting anti-inflammatory and antioxidative activities to ameliorate pathological Tau-mediated mitochondrial dysfunction in a human Tau cell model. The results of this study support the notion that the mulberry leaf extract is a potential disease-modifying therapeutic agent for <span>AD</span>.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106042"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907678","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":"Functional effects of heavy metal exposures on N6-methyladenosine (m6A) methylation and other Epitranscriptomic modifications in the central nervous system","authors":"Niraj Lodhi ,&nbsp;Lauren Powell ,&nbsp;Jay S. Schneider","doi":"10.1016/j.neuint.2025.106064","DOIUrl":"10.1016/j.neuint.2025.106064","url":null,"abstract":"<div><div>Among different RNA methylations, N6-methyladenosine (m6A) is the most abundant in the brain and determines the fate of RNA through reversible processes using methyltransferases, demethylases, and methyl-binding proteins. The reversibility of m6A is an emerging regulatory mechanism for gene expression, regulating many aspects of RNA metabolism and influencing learning and memory processes. Global m6A profiles are dynamically modified via the activity of various writers, readers, and erasers. However, m6A alterations from exposure to heavy metals, including the metals lead (Pb), cadmium (Cd), cobalt (Co), and manganese (Mn) and the metalloid arsenic (As), and the impact on brain function, are not fully understood. This paper reviews recent work that may begin to shed light on how heavy metal exposures may affect m6A methylation and how this might impact central nervous system functioning.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106064"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228432","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}