Neurochemistry international最新文献

{"title":"DUSP1-mediated suppression of p38 MAPK signaling pathway reduces ferroptosis in cerebral ischemia-reperfusion injury.","authors":"Shuyin Ma, Xiaodong Zhang, Jiaxin Fan, Mengying Chen, Qingling Yao, Nan Zhang, Kaili Shi, Minyu Duan, Han Yang, Tiantian Gao, Xiaodong Ma, Jingyi Wang, Weina Li, Chuxiao Zhou, Shuqin Zhan","doi":"10.1016/j.neuint.2025.106024","DOIUrl":"10.1016/j.neuint.2025.106024","url":null,"abstract":"<p><p>Ferroptosis constitutes a critical pathological mechanism in cerebral ischemia-reperfusion injury (CI/RI), significantly influencing neurological outcomes. While dual specificity phosphatase 1 (DUSP1) demonstrates neuroprotective effects against CI/RI, its regulatory role in ferroptosis remains to be elucidated. This study systematically investigated the therapeutic potential of DUSP1 through ferroptosis modulation in both in vitro and in vivo models. Using oxygen-glucose deprivation/reoxygenation (OGD/R)-treated PC12 cells with either DUSP1 overexpression or knockdown, we comprehensively assessed ferroptosis parameters including cell viability, malondialdehyde content, glutathione levels, intracellular iron concentration, reactive oxygen species accumulation, and expression of key ferroptosis-related proteins. In middle cerebral artery occlusion/reperfusion (MCAO/R) rat models, pharmacological inhibition of DUSP1 was employed to evaluate its impact on cerebral infarction volume, neurological deficits, histopathological changes, and ferroptosis biomarkers. Mechanistic studies incorporated the p38 mitogen-activated protein kinase pathway inhibitor adezmapimod. Our results demonstrated that (1) ferroptosis was significantly induced in both the OGD/R and MCAO/R models, accompanied by upregulated DUSP1 expression; (2) DUSP1 overexpression attenuated ferroptosis and ameliorated CI/RI, whereas genetic knockdown exacerbated these pathological processes; (3) pharmacological inhibition of DUSP1 aggravated cerebral injury and ferroptosis markers in MCAO/R rats; and (4) adezmapimod treatment effectively rescued ferroptosis progression in DUSP1-deficient cells by restoring glutathione peroxidase 4 and ferroportin expression while downregulating transferrin receptor and Ferritin Heavy Chain levels. These findings establish that DUSP1 confers neuroprotection against CI/RI through p38-mediated ferroptosis regulation, suggesting its promise as a novel therapeutic target for ischemic stroke.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"106024"},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768181","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":"MUSASHI1 promotes Tau phosphorylation by activating the p38 MAPK pathway.","authors":"Wenshuang Li, Baomiao Ma, Xiang Tian, Qi Xiong, Mengqi Zhou, Wei Liu, Xiji Shu","doi":"10.1016/j.neuint.2025.106066","DOIUrl":"https://doi.org/10.1016/j.neuint.2025.106066","url":null,"abstract":"<p><p>Aberrant phosphorylation of the Tau protein represents a critical event in the pathogenesis of Alzheimer's disease (AD); however, therapeutic interventions specifically targeting this modification remain limited. Therefore, a thorough understanding of the molecular mechanisms underlying Tau hyperphosphorylation is essential for the development of effective preventive and therapeutic strategies against AD. The RNA-binding protein MUSASHI1 (MSI1) is recognized for its significant role in neurodevelopment, and previous studies have reported its dysregulated overexpression in the brains of AD patients. In the current investigation, we demonstrate that MSI1 expression progressively increases in parallel with the advancement of Tau pathology in P301S transgenic mouse models. Furthermore, our findings suggest that MSI1 activates the p38 mitogen-activated protein kinase (MAPK) signaling pathway, thereby promoting Tau phosphorylation. Additionally, we have identified two microtubule-associated proteins as novel potential interaction partners of MSI1 within neuronal cells. Collectively, these results reveal a previously uncharacterized mechanism that may contribute to aberrant Tau phosphorylation in AD, offering new directions for future research in this field.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"106066"},"PeriodicalIF":4.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211323","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":"Spinal p38 MAPK/PGC-1α/SIRT3 signaling pathway mediates remifentanil-induced hyperalgesia in rats via ROS release and NR2B activation.","authors":"Guoyan Feng, Fengxiang Song, Aiqi Wang, Lu Wang, Haotian Zhang, Shun Wang, Haitao Hou, Lianxiang Zhang, Liqin Deng","doi":"10.1016/j.neuint.2025.106061","DOIUrl":"10.1016/j.neuint.2025.106061","url":null,"abstract":"<p><p>Remifentanil-induced hyperalgesia (RIH) poses a significant clinical challenge. Our research group has previously confirmed that abnormal activation of p38 mitogen-activated protein kinase (p38 MAPK) in the spinal dorsal horn contributes to RIH, but the specific regulatory pathway remains unclear. It is known that p38 MAPK can regulate the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and the PGC-1α/Sirtuin 3 (SIRT3) pathway plays an important role in various pain models. However, whether this pathway is involved in RIH remains to be elucidated. In this study, an RIH model was established using male Sprague-Dawley (SD) rats, and significant hyperalgesia was observed in the RIH group. Intrathecal injection of the p38 MAPK inhibitor SB203580 or the PGC-1α agonist ZLN005 significantly alleviated this hyperalgesic response. Mechanistic analysis further revealed that in the RIH model group, activation of p38 MAPK was increased in spinal dorsal horn microglia, while the expression of PGC-1α and SIRT3 were decreased. In neurons, reactive oxygen species (ROS) levels were increased, accompanied by increased expression of the N-methyl-d-aspartate receptor (NMDAR) subunit NR2B, synaptic structural remodeling, and an increase in the amplitude and frequency of NMDAR-mediated spontaneous excitatory postsynaptic currents (sEPSCs). All these pathological changes could be reversed by intervention with either SB203580 or ZLN005. In conclusion, this study demonstrates that remifentanil activates p38 MAPK in spinal dorsal horn microglia, inhibits the PGC-1α/SIRT3 signaling pathway, promotes ROS release, subsequently activates the neuronal NR2B subunit, and ultimately induces RIH. This mechanism provides a new potential target for the treatment of RIH.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"106061"},"PeriodicalIF":4.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184516","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, Xinping Wang, Jijuan Zhao","doi":"10.1016/j.neuint.2025.106063","DOIUrl":"10.1016/j.neuint.2025.106063","url":null,"abstract":"<p><strong>Purpose: </strong>To study the role and mechanism of SPP1 in spinal cord injury.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"106063"},"PeriodicalIF":4.0,"publicationDate":"2025-09-26","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":"Constant light exposure promotes pathogenic tau hyperphosphorylation and phenotypic manifestations in Drosophila disease models","authors":"Prerna Aggarwal ,&nbsp;Virender ,&nbsp;Surajit Sarkar","doi":"10.1016/j.neuint.2025.106060","DOIUrl":"10.1016/j.neuint.2025.106060","url":null,"abstract":"<div><div>Chronic sleep disruption caused by constant artificial light exposure has emerged as both a comorbidity and a precursor of several neurodegenerative disorders, including tauopathies. Tauopathies, a group of neurodegenerative disorders, are characterised by the toxic accumulation of hyperphosphorylated tau in brain neurons. While disturbance in the sleep/wake cycle is an inherent clinical feature of tauopathies, the impact of prolonged light exposure on disease progression and severity has been inadequately investigated. We utilized <em>Drosophila</em> models of human tauopathies to examine the impact of uninterrupted exposure to light on tau-induced phenotypic markers during pathogenesis over a short period of aging. We observed that constant light exposure causes an earlier onset and increased severity of disease-associated phenotypes in an age-dependent manner. We further noted that these aggravated phenotypes are associated with increased pathogenic hyperphosphorylation of tau, leading to the rapid accumulation of relatively larger neurotoxic aggregates in neuronal cells and their subsequent degeneration. Overall, our study demonstrates that unhealthy light exposure accelerates the early onset and severity of tauopathy-related phenotypes, highlighting its potential relevance in developing management strategies for these devastating neurodegenerative disorders.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106060"},"PeriodicalIF":4.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154328","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":"Genetic and Epigenetic Architectures of Stroke: Insights from GWAS to Precision Medicine.","authors":"Faheem Shehjar, Reetika Mahajan, Shayaan Shahnaz, Zahoor A Shah","doi":"10.1016/j.neuint.2025.106059","DOIUrl":"https://doi.org/10.1016/j.neuint.2025.106059","url":null,"abstract":"<p><p>Stroke remains a leading cause of death and disability, driven by complex interactions among genetic, epigenetic, and environmental factors. Advances in genomic technologies have elucidated the role of common polygenic variants and rare monogenic mutations in determining susceptibility to stroke subtypes. Genome-wide association studies have identified key loci, including Histone Deacetylase 9 (HDAC9), Paired-like Homeodomain Transcription Factor 2 (PITX2), Zinc Finger Homeobox 3 (ZFHX3), and Collagen Type IV Alpha 1 Chain (COL4A1), associated with vascular inflammation, atrial fibrillation, and small vessel dysfunction. Monogenic disorders such as Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL; NOTCH3), Fabry disease (GLA), and Sickle Cell Disease (SCD; HBB) illustrate the impact of single-gene mutations on early-onset or familial stroke. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) regulate pathways related to apoptosis, inflammation, angiogenesis, and blood-brain barrier dysfunction. Pharmacogenomic profiling, involving genes such as CYP2C19, VKORC1, and SLCO1B1, can guide individualized therapy with antiplatelets, anticoagulants, and statins. Collectively, these advances are steering stroke care toward precision medicine, integrating multi-omics data and gene-targeted strategies for improved prevention, diagnosis, and treatment.</p>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":" ","pages":"106059"},"PeriodicalIF":4.0,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172167","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":"Neuronutritional enhancement of antioxidant defense system through Nrf2/HO1/NQO1 axis in fibromyalgia","authors":"Francesca Inferrera ,&nbsp;Nicla Tranchida ,&nbsp;Roberta Fusco ,&nbsp;Salvatore Cuzzocrea ,&nbsp;Daniela Impellizzeri ,&nbsp;Rosalba Siracusa ,&nbsp;Ramona D'Amico ,&nbsp;Luay Rashan ,&nbsp;Anastasiia Badaeva ,&nbsp;Alexey Danilov ,&nbsp;Vittorio Calabrese ,&nbsp;Rosanna Di Paola ,&nbsp;Marika Cordaro","doi":"10.1016/j.neuint.2025.106057","DOIUrl":"10.1016/j.neuint.2025.106057","url":null,"abstract":"<div><div>Fibromyalgia (FM) is a disorder characterized by chronic widespread musculoskeletal pain, and it is often accompanied by fatigue, sleep disturbance, and cognitive dysfunction. Although pathophysiology is multifactorial, increasing evidence highlights the pivotal role of oxidative stress and mitochondrial dysfunction in the development of this condition. In particular, the Nrf2/HO-1/NQO1 antioxidant axis plays a crucial role in counteracting oxidative damage and maintaining cellular homeostasis. Boswellia (BS) is a genus of plants in the Burseraceae family, which includes around twenty species found across sub-Saharan Africa, the Arabian Peninsula, and the Indian subcontinent. In Ayurvedic medicine, it has traditionally been used in the treatment of diabetes, fever, as well as certain cardiovascular, dermatological, and neurological conditions. Boswellic acids are thought to possess anti-inflammatory, anti-rheumatic, and pain-relieving properties. The purpose of this study was to investigate the beneficial effects of BS extract in a murine model of reserpine-induced FM. Following reserpine administration, markers of oxidative stress, neuroinflammation, and behavioral changes including mechanical allodynia, hyperalgesia, anxiety, and depression-like behaviors were significantly increased. Daily oral administration of BS at a dose of 100 mg/kg effectively restored these pathological changes. BS oral supplementation, by preventing microglia and astrocyte activation, as demonstrated by decreased GFAP and Iba-1 expression, BS decreased neurological inflammation and restored neurotransmitter levels such as norepinephrine, dopamine and serotonin. Futhermore, improved antioxidant defenses by increasing nuclear translocation of Nrf2 and subsequent expression of its downstream targets, HO-1 and NQO1, limiting lipid peroxidation and ROS production. According to behavioral tests, BS significantly reduced the emotional deficit and mechanical sensitivity linked to FM. Our findings indicate that BS integration has neuroprotective effects, acting on oxidative stress and neuroinflammation, and suggesting that it is a viable natural strategy for managing FM symptoms.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106057"},"PeriodicalIF":4.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147246","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":"Two phosphomimetic sites in the GABA transporter GAT1 C-terminus selectively regulate transporter interactions with distinct types of PDZ domains in vitro","authors":"Iveta Koščová,&nbsp;Martina Baliova,&nbsp;Frantisek Jursky","doi":"10.1016/j.neuint.2025.106058","DOIUrl":"10.1016/j.neuint.2025.106058","url":null,"abstract":"<div><div>The GABA transporter GAT1 is a membrane protein that participates in GABA signalling in the brain and certain peripheral tissues. GAT1 contains a C-terminal PDZ motif (-A⁵⁹⁷Y⁵⁹⁸I⁵⁹⁹), previously classified as a type II (ΦXΦ) motif, where PDZ interaction should depend on non-phosphorylatable hydrophobic (Φ) residues at PDZ positions 0 (I⁵⁹⁹) and −2 (A⁵⁹⁷). We recently found that a GAT1 C-terminal peptide unconventionally binds to the PDZ1 domain of syntenin-1 and to the PDZ2 domain of PSD95 by using different PDZ interaction schemes, specifically 0,-1 and 0,-3, respectively. In this work, we used phosphomimetic amino acid mutagenesis to investigate the role of phosphorylatable amino acids in the GAT1 C-terminus in binding to these two domains. The mutagenesis and molecular docking experiments suggested that phosphorylation of tyrosine 598 at PDZ position −1 might affect the interaction with the PDZ1 domain of syntenin-1, but it did not affect the interaction with the PDZ2 domain of PSD95. On the other hand, a phosphomimetic but not a neutral mutation of the remote serine residues 592 and 594 at PDZ positions −7 and −5, respectively, affected the interaction of the GAT1 PDZ motif with the PDZ2 domain of PSD95, but not with the PDZ1 domain of syntenin-1. These findings suggest the existence of at least two domain-specific GAT1 PDZ interaction modes regulated by two distinct potentially phosphorylatable serine and tyrosine residues in the GAT1 C-terminus.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106058"},"PeriodicalIF":4.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136082","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 antidepressant venlafaxine induces upregulation of miR-92 and histological alterations in a chicken embryo model","authors":"Oykum Kaplan-Arabaci ,&nbsp;Denis Zosen ,&nbsp;Diana Domanska ,&nbsp;Sigrid Bjørnstad ,&nbsp;Simone Santini ,&nbsp;Umut Karaca ,&nbsp;Jasmin Andrea Haeckel ,&nbsp;Kristine Dolva ,&nbsp;Zuzana Dančišinová ,&nbsp;Fred Haugen ,&nbsp;Jannike Mørch Andersen ,&nbsp;Ragnhild Elisabeth Paulsen","doi":"10.1016/j.neuint.2025.106056","DOIUrl":"10.1016/j.neuint.2025.106056","url":null,"abstract":"<div><div>Antidepressants are commonly prescribed for treating anxiety disorders and depression, including pregnant patients. These medications influence the absorption and metabolism of key neurotransmitters such as serotonin, norepinephrine, and dopamine. However, many aspects of antidepressant function remain unclear, especially regarding their impact on neurodevelopment when used during pregnancy. To explore this, we employed a 3R-friendly chicken embryo model to investigate the cellular and molecular implications of antidepressants use. We focused on commonly used antidepressants for the study: escitalopram, which is a selective serotonin reuptake inhibitor; and venlafaxine, a serotonin and noradrenaline reuptake inhibitor, both of which are frequently prescribed during pregnancy.</div><div>Drug distribution analysis showed that both antidepressant drugs reached clinical concentrations in the brain of developing chicken embryos and persisted for several hours. High-throughput miRNA-sequencing showed that venlafaxine upregulated 13 different miRNAs in the chicken cerebellum. Specifically, miR-92 and its human ortholog, miR-363, were significantly upregulated in chicken cerebellum and neuronally differentiated human SH-SY5Y cells, respectively. Neurite metrics showed a significant reduction in neurite outgrowth with venlafaxine, but not with escitalopram. Furthermore, venlafaxine caused histological alterations, such as increased white matter and reduced thickness of the cortical and molecular layer in the cerebellum. Both drugs reduced the thickness of the external granular layer and the number of mitotic events, impacting this crucial germinal zone of the brain.</div><div>These findings highlight distinct neurodevelopmental effects of escitalopram and venlafaxine and raise awareness for potential adverse neurological effects in offspring exposed to antidepressants in utero.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"190 ","pages":"Article 106056"},"PeriodicalIF":4.0,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124128","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":"2025-09-18","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}