Experimental Neurology最新文献

{"title":"Corrigendum to “Deep brain stimulation electrode modeling in rats” [Volume 350, 2022, 113978, ISSN 0014-4886]","authors":"Andrea Andree , Ningfei Li , Konstantin Butenko , Maria Kober , Jiazhi Chen , Takahiro Higuchi , Mareike Fauser , Alexander Storch , Chi Wang Ip , Andrea A. Kühn , Andreas Horn , Ursula van Rienen","doi":"10.1016/j.expneurol.2025.115221","DOIUrl":"10.1016/j.expneurol.2025.115221","url":null,"abstract":"","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"388 ","pages":"Article 115221"},"PeriodicalIF":4.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrodin alleviates Aβ25–35-induced glycolytic dysfunction via activating PI3K/AKT/BACH1 signaling in Alzheimer's disease models","authors":"Ting-Ting Liu ,&nbsp;Xue Yang ,&nbsp;Hui-Ping Lei ,&nbsp;Yue-Ting Hu ,&nbsp;Ling-Nan Wu ,&nbsp;Ai-Hong Wei ,&nbsp;Xin-Hao Ji ,&nbsp;Ju Liu ,&nbsp;Hai Jin ,&nbsp;Jing-Shan Shi ,&nbsp;Shao-Yu Zhou ,&nbsp;Feng Jin","doi":"10.1016/j.expneurol.2025.115225","DOIUrl":"10.1016/j.expneurol.2025.115225","url":null,"abstract":"<div><div>Cerebral glycolytic alteration has been identified as an important contributor to the pathological progress of Alzheimer's disease (AD). Research has shown that gastrodin (GAS) possesses neuroprotection in various experimental models of AD, but its specific mechanism remains unclear. In this study, we determined whether GAS exerted neuroprotective effects on AD models through regulating PI3K/AKT/BACH1 signaling axis. Eight-week-old C57BL/6 J male mice were intracerebroventricularly injected with Aβ_25–35, to establish an AD model, followed by the administration of GAS (30, 60 mg·kg⁻¹·d⁻¹, i.g.) for 21 days. Treatment of GAS markedly alleviated the downregulation of p-PI3K Tyr199/458, p-AKT Ser473, BACH1 and HK1 in the hippocampus of the Aβ_25–35-induced AD mice. To further explore the mechanism of GAS-mediated neuroprotection, an in vitro AD cellular model was established by challenging HT22 cells with Aβ_25–35. In the Aβ_25–35 induced cells, the expression of BACH1, p-PI3K Tyr199/458 and p-AKT Ser473 was reduced, the mRNA and protein levels of HK1 were decreased, and the levels of pyruvate and ATP were reduced. After treatment of GAS, the decline of these indicators was reversed. In addition, overexpression of BACH1 by lentivirus transfection significantly upregulated the mRNA and protein levels of HK1, thereby enhancing glycolytic function and protecting HT22 cells from Aβ_25–35-induced injury. The results of chromatin immunoprecipitation assay-real-time quantitative PCR revealed that BACH1 directly bound to the HK1 promoter region. Collectively, these findings suggest that GAS can play a protective role in Aβ_25–35-induced experimental AD models by increasing HK1 expression and ameliorating glycolytic dysfunction through activation of the PI3K/AKT/BACH1 signaling axis.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"389 ","pages":"Article 115225"},"PeriodicalIF":4.6,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of long-term deltamethrin exposure on Alzheimer's-related neurodegeneration in rats","authors":"Serdar Altun ,&nbsp;Selçuk Özdemir ,&nbsp;Harun Arslan ,&nbsp;Metin Kiliçlioğlu ,&nbsp;Esra Yaprak ,&nbsp;İsmail Bolat ,&nbsp;Şeyma Aydın","doi":"10.1016/j.expneurol.2025.115223","DOIUrl":"10.1016/j.expneurol.2025.115223","url":null,"abstract":"<div><div>In recent years, epidemiological studies have emerged indicating a potential association between chronic exposure to pesticides and the development of chronic neurodegenerative nervous system diseases such as Alzheimer's disease. In this study, we aimed to investigate the potential role of long-term nonfatal exposure to Deltamethrin in spreading this disease. To this end, a range of aspects of brain damage were discussed in rats administered deltamethrin in oral doses of 0.65 mg/kg b.w. and 1.3 mg/kg b.w. for 30 days. The activation of beta-amyloid, the primary component of plaques characteristic of Alzheimer's disease, and the NG2, a type 1 transmembrane protein, was assessed by immunohistochemistry and western blot methods in rat brain. In addition, the expression level of the APP, GFAP, NfL, TNF-alpha, CXCL9, CCL5, and IL-1 alpha genes in deltamethrin-exposed brain tissue was measured using qRT-PCR. In addition, levels of pTau181 and Abeta42 were measured with ELISA. A strong positive immunohistochemical reaction for beta-amyloid was detected in the deltamethrin-exposed brain tissues. A decrease in NG2 immunofluorescence positivity was found in the application groups compared to the control group. It was demonstrated that deltamethrin exposure significantly up-regulated the expressions of APP, GFAP, NfL, TNF-alpha, CXCL9, CCL5, and IL-1 alpha genes, also significantly higher the levels of pTau181 and Abeta42 (pg/ml) in rat brain tissues.</div><div>This study provides scientific evidence that exposure to chronic doses of deltamethrin may play a positive role in the development of diseases such as Alzheimer's. Future studies should investigate similar projects and expand knowledge on the topic.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"388 ","pages":"Article 115223"},"PeriodicalIF":4.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of effects of Resolvin D1 after spinal cord injury in mice","authors":"Isaac Francos-Quijorna ,&nbsp;Néstor López-González ,&nbsp;Marc Caro-Canton ,&nbsp;Alba Sánchez-Fernández ,&nbsp;Gerard Hernández-Mir ,&nbsp;Rubèn López-Vales","doi":"10.1016/j.expneurol.2025.115226","DOIUrl":"10.1016/j.expneurol.2025.115226","url":null,"abstract":"<div><div>Inflammation is a fundamental component of the body's response to injury or infection and is responsible for restoring tissue homeostasis and starting the wound healing process. To avoid excessive tissue damage, it is important to efficiently resolve inflammation once it is no longer necessary. In recent years, the discovery of pro-resolving lipid mediators derived from polyunsaturated fatty acids, such as Resolvin D1 (RvD1), has shed light on the resolution of inflammation. However, the impact of RvD1 on Spinal Cord Injury (SCI) remains unexplored. In this study, we provide direct evidence that the administration of RvD1 for one week after SCI fails to enhance resolution of inflammation and does not improve functional and histological outcomes. Our transcriptomic analysis reveals that RvD1 does not modulate inflammatory response pathways in the injured spinal cord but leads to significant changes in the expression of genes related to ribosomal function and extracellular matrix pathways. Unlike SCI, RvD1 treatment ameliorated neurological deficits in experimental autoimmune encephalomyelitis. Our findings represent the first report demonstrating that RvD1 treatment does not exert therapeutic actions in the context of SCI and suggest that this pro-resolving agonist may exert therapeutic actions in certain but not in all conditions involving an inflammatory component.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"388 ","pages":"Article 115226"},"PeriodicalIF":4.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promotion of remyelination by a thyromimetic drug leading to functional recovery","authors":"Ian D. Duncan ,&nbsp;Jeffrey A. Vivian ,&nbsp;Benjamin K. August ,&nbsp;Nicholas S. Keuler ,&nbsp;Abigail Komro ,&nbsp;Daniel Radecki ,&nbsp;Julie A. Kiland ,&nbsp;Rohan Gandhi ,&nbsp;Madelyn Reilly ,&nbsp;Starr Cameron ,&nbsp;Helena Rylander ,&nbsp;Jessica Pritchard ,&nbsp;James N. Ver Hoeve","doi":"10.1016/j.expneurol.2025.115227","DOIUrl":"10.1016/j.expneurol.2025.115227","url":null,"abstract":"<div><div>Promotion of remyelination has become a critical therapeutic approach in the treatment of demyelinating disorders including multiple sclerosis (MS), both to restore function and protect intact axons against future degeneration. Thyroid hormone receptor agonist mediated signaling is critical for the maturation of oligodendrocytes (Ols) from oligodendrocyte precursor cells (OPCs) and may be a rational target for drug development in the treatment of MS. Therefore, we tested the potential of a thyromimetic drug pro-drug, LL-341070, to promote remyelination and neurologic recovery in a unique large animal model in which there is extensive demyelination throughout the CNS that results from the prolonged feeding of irradiated food. In four out of eight cats fed the irradiated diet that had developed significant neurologic dysfunction, daily treatment with LL-341070 led to clinical improvement or complete recovery of baseline function. Extensive evidence of remyelination was observed throughout the brain, spinal cord and in the optic nerve in these four animals when compared with non- treated animals. These results provide support for thyroid hormone receptor agonism as a potential novel target to promote remyelination and clinical outcomes in patients with MS.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"389 ","pages":"Article 115227"},"PeriodicalIF":4.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redefining macrophage phenotypes after spinal cord injury: An open data approach","authors":"Fernanda Stapenhorst França,&nbsp;John C. Gensel","doi":"10.1016/j.expneurol.2025.115222","DOIUrl":"10.1016/j.expneurol.2025.115222","url":null,"abstract":"<div><div>Spinal cord injury (SCI) triggers intraspinal inflammation through an influx of blood-derived inflammatory cells such as neutrophils and monocyte-derived macrophages. Macrophages play a complex role in SCI pathophysiology ranging from potentiating secondary injury to facilitating recovery and wound healing. In vitro, macrophages have been classified as having a pro-inflammatory, M1 phenotype, or a regenerative, M2 phenotype. In vivo, however, studies suggest that macrophages exist in a spectrum of phenotypes and can shift from one phenotype to another. Single-cell RNA sequencing (scRNA-seq) allows us to assess immune cell heterogeneity in the spinal cord after injury, and several groups have created publicly available datasets containing valuable data for further exploration. In this study, we compared three different scRNA-seq datasets and analyzed macrophage heterogeneity after SCI based on cell clustering according to gene expression profiles. We analyzed data from 7 days post injury (dpi) in young female mice that received a mid-thoracic SCI contusion. Using the Seurat pipeline, we clustered cells, subsetted macrophages from microglia and other myeloid cells, and identified different macrophage populations. Using SingleR as a cross-dataset cluster comparison tool, we identified similarities in macrophage populations across datasets. To confirm and refine this analysis, we analyzed the top 10 differentially expressed genes for each population in each dataset. Most clusters identified in the SingleR analysis were confirmed to have a unique genetic signature and were consistently present in all datasets analyzed. Taken together, four distinct macrophage populations were consistently identified after SCI at 7 dpi in three datasets from independent research teams. Our identification of biologically conserved macrophage populations after SCI using an unbiased approach highlights the power of data sharing and open data in redefining macrophage heterogeneity.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"388 ","pages":"Article 115222"},"PeriodicalIF":4.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural stem cell-derived exosomes improve neurite outgrowth and cognitive function through transferring miR-132-3p","authors":"Yan Wang ,&nbsp;Jia Zhao ,&nbsp;Qian Guo ,&nbsp;Yulan Yin ,&nbsp;Wanjun Tian ,&nbsp;Xiaoxia Wang ,&nbsp;Ganwen Deng ,&nbsp;Qunwen Pan ,&nbsp;Xiaotang Ma","doi":"10.1016/j.expneurol.2025.115224","DOIUrl":"10.1016/j.expneurol.2025.115224","url":null,"abstract":"<div><h3>Background/aims</h3><div>Vascular dementia (VD) is accompanied by severe neuronal damage. Exosomal microRNAs (miRs) have been implicated in the neuroprotective effect of neural stem cells (NSCs), and miR-132-3p is a proneurogenic miR. In this study, we aimed to explore the role and underlying mechanisms of miR-132-3p-enriched NSC-EXs in VD-induced neuronal damage and synaptic impairment.</div></div><div><h3>Methods</h3><div>NSC-EXs, NSC-EXs enriched with miR-132-3p (NSC-EXs^miR-132-3p), and NSC-EXs deficient in miR-132-3p (NSC-EXs^simiR-132-3p) were cocultured with oxygen- and glucose-deprived (OGD)-injured neurons or administered to VD mice. Bioinformatic analyses and luciferase assays were used to determine the target genes of miR-132-3p.</div></div><div><h3>Results</h3><div>The levels of NSC-EXs and their associated miR-132-3p were markedly decreased in the hippocampi of VD mice. Compared with NSC-EXs, the infusion of NSC-EXs^miR-132-3p was more effective at increasing the miR-132-3p level, neuron number, dendritic spine density and cognitive function and decreasing neuronal ROS production and apoptosis, whereas NSC-EXs^simiR-132-3p treatment resulted in attenuated effects in comparison with those of NSC-EXs. In OGD-treated neurons, incubation with NSC-EXs^miR-132-3p increased neurite outgrowth and decreased neuronal ROS production and apoptosis. Moreover, through bioinformatic analysis and cell transfection, we confirmed that NSC-EXs^miR-132-3p promoted neurite outgrowth by targeting RASA1 and increasing the expression of downstream Ras and the phosphorylation of ERK1/2.</div></div><div><h3>Conclusions</h3><div>Our findings indicate that miR-132-3p enrichment promotes the efficacy of NSC-EXs in treating VD-induced neuronal damage and synaptic impairment via the inhibition of RASA1 and the activation of the downstream Ras/ERK1/2 signaling pathway.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"388 ","pages":"Article 115224"},"PeriodicalIF":4.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPM1D ameliorates Alzheimer's disease by promoting mitophagy","authors":"Aiming Wang ,&nbsp;Fan Zhang ,&nbsp;Wenqiang Zhang ,&nbsp;Jian Gong ,&nbsp;Xiaohong Sun","doi":"10.1016/j.expneurol.2025.115218","DOIUrl":"10.1016/j.expneurol.2025.115218","url":null,"abstract":"<div><div>Mitochondrial autophagy (mitophagy) plays an essential role in the maintenance of mitochondrial homeostasis. Defective mitophagy triggered by amyloid beta (Aβ) is linked to neuronal deterioration and neurodegeneration in Alzheimer's disease (AD). However, the molecular mechanism underlying the defective mitophagy in AD is still not fully illustrated. Protein phosphatase Mn²⁺/Mg²⁺-dependent 1D (PPM1D) triggers autophagy in mouse embryonic fibroblasts. Downregulated PPM1D was shown in the hippocampus of APP/PS1 mice. This study aims to investigate the role of PPM1D in the progression of AD. Here, APP/PS1 mice were used to mimic AD, and rAAV2 vectors expressing PPM1D were injected into the bilateral hippocampus. <em>In vitro</em>, the mouse hippocampal neuron cell line HT22 was stimulated by Aβ₁_–₄₂ to trigger neuronal damage. High PPM1D expression alleviated the impairments of spatial cognition and memory in APP/PS1 mice. Additionally, PPM1D enhanced autophagosome formation, lysosomal degradation of impaired mitochondria, amyloid plaque deposition, and neuronal degeneration and apoptosis in the hippocampus of APP/PS1 mice. Similar effects of PPM1D on neuronal apoptosis and mitophagy were observed in Aβ₁_–₄₂-treated HT22 cells, and the effects could be reversed by the mitophagy inhibitor cyclosporine A. In conclusion, PPM1D facilitates mitophagy to inhibit the progression of AD-like disease. Taken together, the present work uncovers defective mitophagy in AD may be associated with down-regulated PPM1D, and PPM1D may be a potential therapeutic target for AD treatment.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"388 ","pages":"Article 115218"},"PeriodicalIF":4.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guanine and isoguanine promote axon regeneration of dorsal root ganglion neurons and survival of retinal ganglion cells after injury","authors":"Hui Li,&nbsp;Junjie Yan,&nbsp;Zixin Wan,&nbsp;Junjie Zhang,&nbsp;Shishi Wu,&nbsp;Bin Yu,&nbsp;Susu Mao","doi":"10.1016/j.expneurol.2025.115219","DOIUrl":"10.1016/j.expneurol.2025.115219","url":null,"abstract":"<div><div>Neurological injuries usually lead to motor, sensory, or cognitive impairment, which urgently need the development of effective therapeutic strategies. An increasing number of studies have indicated that metabolites can serve as therapeutic drugs for treating diseases or repairing damaged tissues. Among them, purines and their derivatives have shown the neuroprotection effects in the nervous system and garnered significant focus in the field of pharmaceutical development. In the present study, we found that the level of isoguanine in the dorsal root ganglion (DRG) was decreased after sciatic nerve injury. Functional investigations revealed that isoguanine and its isomer, guanine, promote axon growth of primary DRG neurons <em>in vitro</em> and enhance axon regeneration <em>in vivo</em> in the peripheral nervous system (PNS) by activating Akt signaling. Conversely, in the central nervous system (CNS), both guanine and isoguanine could not induce the regeneration of the optic nerve; instead, they enhance the survival of retinal ganglion cells after optic nerve crush injury. Collectively, these data provide experimental evidence supporting guanine and isoguanine as promising therapeutic candidates for the management of neurological injuries within both the PNS and CNS.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"388 ","pages":"Article 115219"},"PeriodicalIF":4.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activating Wnt1/β-Catenin signaling pathway to restore Otx2 expression in the dopaminergic neurons of ventral midbrain","authors":"Zhao Li ,&nbsp;Jinhai Duan ,&nbsp;AnQi Cao ,&nbsp;Zhuo Gong ,&nbsp;Hao Liu ,&nbsp;Danyang Shen ,&nbsp;Tonglin Ye ,&nbsp;Shunyan Zhu ,&nbsp;Qikai Cen ,&nbsp;Shuaiying He ,&nbsp;Yongqian He ,&nbsp;Canbing Zheng ,&nbsp;Xian Lin","doi":"10.1016/j.expneurol.2025.115216","DOIUrl":"10.1016/j.expneurol.2025.115216","url":null,"abstract":"<div><div>Parkinson's disease (PD) is the world's second most prevalent neurodegenerative disease. Currently, aside from levodopa, there are no other effective drugs clinically available to slow its progression. Otx2 plays a critical role in the differentiation of midbrain dopaminergic neurons (mDANs) during midbrain development. However, in adulthood, Otx2 is primarily expressed in the ventral tegmental area (VTA)-ventral part, and mDANs in the dorsal part of the VTA and the substantia nigra pars compacta (SNc) show no Otx2 expression. Research indicates that Otx2 is essential not only for the development of mDANs but also for their protection against the toxicity of MPTP and rotenone. Consequently, Otx2 is a potential clinical target for mDANs protection. Identifying the upstream mechanism that regulates Otx2 expression is crucial to restoring its expression in the SNc and enhancing its levels in the entire ventral midbrain mDANs. In this study, we have demonstrated the safety of Otx2 overexpression in vitro by using adeno-associate virus (AAV) and explored the feasibility of promoting Otx2 expression through the Wnt/β-Catenin signaling pathway using various drugs, a miR-34 mimic, and an inhibitor. Our results showed that Otx2 overexpression via AAV in the SNc is relatively safe, and CHIR99021 can induce Otx2 expression in mouse mDANs, thereby, alleviating PD-liked motor symptoms induced by MPTP. These findings suggest that modulating Otx2 expression through the Wnt/β-Catenin signaling pathway holds a therapeutic approach for Parkinson's disease.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"388 ","pages":"Article 115216"},"PeriodicalIF":4.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}