Journal of Molecular Neuroscience最新文献

{"title":"Machine Learning Identifies FLNA as a Key Molecular Target Regulating Neuronal Apoptosis after Spinal Cord Injury","authors":"Yingfan Pei,&nbsp;Yaorui Hu,&nbsp;Guoying Feng,&nbsp;Qing Xu,&nbsp;Shuai Zhou,&nbsp;Naili Zhang,&nbsp;Chunlei Zhang,&nbsp;Fei Huang,&nbsp;Luping Zhang","doi":"10.1007/s12031-025-02439-z","DOIUrl":"10.1007/s12031-025-02439-z","url":null,"abstract":"<div><p>Spinal cord injury (SCI), a traumatic type of central nervous system injury, is closely associated with neuronal apoptosis. However, the specific biomarkers and regulatory mechanisms of neuronal apoptosis in SCI patients remain unclear. In this study, we aimed to identify differentially expressed proteins (DEPs) that regulate neuronal apoptosis after SCI and reveal potential diagnostic and therapeutic targets. Spinal cord tissues were collected for LC‒MS/MS analysis at five different time points after injury. Enrichment analysis, WGCNA, random forest, support vector machine recursive feature elimination, and receiver operating characteristic (ROC) curve analysis methods were used to identify proteins and pathways associated with neuronal apoptosis. Validation was performed using a rat model and PC12 cells. A total of 351 DEPs were identified. By integrating DEPs, WGCNA, and machine learning methods, filamin A (FLNA), an apoptosis-related protein, was identified. The reliability of this finding was confirmed in the above three datasets. Spearman correlation analysis was performed to identify the top 100 proteins whose expression correlated with that of FLNA, which were then subjected to enrichment analysis. GO enrichment analysis and KEGG enrichment analysis revealed that expression of these proteins was enriched in mitochondrial oxidative phosphorylation. Western blot and qRT‒PCR analyses confirmed the upregulation of FLNA expression in a rat model of SCI. In vitro experiments revealed that silencing FLNA expression using siRNA reduced H₂O₂-induced apoptosis and ROS production in PC12 cells. Additionally, FLNA expression knockdown inhibited the PI3K/AKT signalling pathway. FLNA is a critical molecular target for neuronal apoptosis following SCI.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12619718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytosterols from Rosaceae Species as Dual Modulators of Neuroinflammation and Induced Pluripotency","authors":"Fahad M. Alshabrmi","doi":"10.1007/s12031-025-02441-5","DOIUrl":"10.1007/s12031-025-02441-5","url":null,"abstract":"<div><p>Neuroinflammation is a central pathological hallmark of numerous neurodegenerative disorders, often linked to oxidative stress, immune dysregulation, and neuronal dysfunction. Recent advances in regenerative medicine highlight induced pluripotent stem cells (iPSCs) as a powerful tool for cellular reprogramming and neurorestoration. In this study, we explored the therapeutic potential of phytosterols derived from Rosaceae species as dual modulators of neuroinflammation and pluripotency induction. Transcriptomic datasets comprising 42 patient samples (GSE176101, GSE200674, and GSE225031) were analyzed to identify differentially expressed genes (DEGs) associated with neuroinflammatory signaling and stemness regulation. Functional enrichment and pathway analyses revealed significant involvement of inflammatory cascades, oxidative stress responses, and neuroprotective mechanisms. Network pharmacology and protein–ligand interaction studies identified EGFR, ACHE, and PRKCG as critical molecular targets. Molecular docking and molecular dynamics simulations further validated the stable binding affinity of Rosaceae-derived phytosterols with these proteins. Collectively, our findings suggest that phytosterols from Rosaceae species hold promise as multifunctional agents capable of attenuating neuroinflammation while simultaneously promoting iPSC generation, thus providing a novel framework for therapeutic strategies in neurodegenerative disease management.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial Necroptosis Mediated by RIPK3 Leads to Retinal Ganglion Cell Apoptosis Through the Release of FGF2 After Ischemia/Reperfusion","authors":"Jian Liu,&nbsp;Anping Ma,&nbsp;Guangyi Huang,&nbsp;Wen Hu,&nbsp;Xin Xu,&nbsp;Rong Huang,&nbsp;Yaguang Hu,&nbsp;Qiaochu Cheng,&nbsp;Yanlin Feng,&nbsp;Dan Ye,&nbsp;Fan Xu,&nbsp;Aimin Sang","doi":"10.1007/s12031-025-02429-1","DOIUrl":"10.1007/s12031-025-02429-1","url":null,"abstract":"<div><p>The aim of this study was to explore the function of receptor-interacting protein kinase 3 (RIPK3) on retinal neuron damage induced by retinal ischemia/reperfusion (IR). Microglia-specific RIPK3 knockout (KO) mice were employed to establish retinal IR models. Retinal structural and functional status was assessed using hematoxylin and eosin staining along with electroretinogram. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was employed to detect the situations of apoptotic cell death. Immunofluorescence and western blot were applied to detect the proteins associated with necroptosis and retinal inner neurons. Following retinal IR, necroptosis-related protein RIPK3 became activated within microglia, inducing the activation of mixed lineage kinase domain-like protein (MLKL). RIPK3 KO significantly alleviated IR-induced retinal morphological defects and protected against IR-induced visual dysfunction by preserving neurons within the retina. Additionally, the counts of TUNEL⁺ apoptotic cells were markedly reduced within RIPK3 KO mice after IR, along with a decrease in retinal inflammatory responses. Mechanistically, IR injury promoted retinal ganglion cells (RGCs) death by activating RIPK3 to induce MLKL and fibroblast growth factor 2 (FGF2) activation; however, RIPK3 KO suppressed this process. After IR, RIPK3-mediated necroptosis in microglia induced its activation, promoting inflammatory responses and thereby facilitating RGCs death. Targeting RIPK3 could protect retinal neurons from injury after IR through suppressing the MLKL/FGF2 pathway, rendering this a potential curative measure for RGCs degeneration in ischemic retinopathy.\u0000</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145456369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EPG5-Related Disorders in Seven New Patients: Refining the Phenotypic Spectrum and Insights on Phenotype-Genotype Correlations","authors":"Sherif F. Abdel-Ghafar,&nbsp;Amr E. Ahmed,&nbsp;Eman T. Mohammed,&nbsp;Ghada M. H. Abdel-Salam,&nbsp;Mohamed S. Abdel-Hamid,&nbsp;Maha S. Zaki","doi":"10.1007/s12031-025-02419-3","DOIUrl":"10.1007/s12031-025-02419-3","url":null,"abstract":"<div><p>Pathogenic variants in <i>EPG5</i> have been associated with Vici syndrome (OMIM #242840) characterized by agenesis of the corpus callosum (ACC), cataracts, cardiomyopathy, hypopigmentation, and immunodeficiency as hallmark features. Additional variable features include microcephaly, hypotonia, developmental delay, and growth retardation. Recently, few reports described milder cases with a neurodevelopmental phenotype and less systemic involvement harboring <i>EPG5</i> variants suggesting a broader clinical spectrum. Herein, we describe seven patients from six unrelated Egyptian families in whom exome sequencing identified six homozygous (five novel and one previously reported) <i>EPG5</i> variants. Patients presented with global developmental delay, microcephaly, hypotonia, dystonia, and failure to thrive. Seizures were evident in two patients and showed a variable response to antiepileptic drugs. Fair color of hair and skin was noted in four out of seven patients (57%), while cataracts and cardiomyopathy were observed in one patient each (14%). In addition to ACC, cerebellar and pontine hypoplasia, delayed myelination, and ventricular dilatation were evident in all patients. Interestingly, deep fissure in the frontal lobes, extending from the frontal horn to the frontal pole, was documented in six patients and appears to represent a characteristic feature associated with <i>EPG5</i> variants. Our study highlights the phenotypic variability associated with <i>EPG5</i> variants and emphasizes the presence of a phenotypic spectrum ranging from the classic severe Vici syndrome to a neurodevelopmental disorder with less systemic manifestations and a longer survival rate.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabinoids and ADHD: a New Frontier in Neuropharmacology?","authors":"Helia Mavaddat,&nbsp;Abtin Fouladi,&nbsp;Ayeh Sabbagh Kashani,&nbsp;Illia Khayatan,&nbsp;Kamyab Andarzbaksh,&nbsp;Seyed Mehrad Razavi,&nbsp;Amir Rezazadeh","doi":"10.1007/s12031-025-02435-3","DOIUrl":"10.1007/s12031-025-02435-3","url":null,"abstract":"<div><p>Attention deficit hyperactivity disorder (ADHD) is a disorder characterized by symptoms of inattention, impulsivity, and hyperactivity, which can significantly impair individuals’ quality of life and lead to various challenges in their social interactions, relationships, professional endeavors, and academic pursuits. This disorder can manifest in both children and adults, and it has been established that genetic and environmental factors contribute to its etiology. Existing data indicate that individuals with ADHD are at a higher risk of substance use, and some may develop cannabis dependence or engage in self-medication with it. It has been hypothesized that individuals with ADHD may utilize cannabis to mitigate certain symptoms, such as anxiety, or to alleviate the adverse effects of their prescribed medication. Furthermore, both in vivo and clinical investigations have reported that cannabinoids, including cannabidiol, may possess potential therapeutic effects in ADHD patients or animal models. This study aims to provide a comprehensive review of the current literature on the impact of cannabinoids on ADHD and to elucidate the possible pharmacological mechanisms through which cannabinoids might exert their therapeutic outcomes.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145406190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unconventional Non-rodent Models in Neurological Research: Exploring New Paths to Translational Insights","authors":"Arti Devi,&nbsp;Chandra Shekhar Saini,&nbsp;Aditya Shiven,&nbsp;Ashwani Kumar,&nbsp;Anisha Sharma,&nbsp;Naman Joshi,&nbsp;Sajpreet Kour,&nbsp;Zaved Ahmed Khan,&nbsp;Hitesh Dewangan,&nbsp;Vagish Dwibedi","doi":"10.1007/s12031-025-02408-6","DOIUrl":"10.1007/s12031-025-02408-6","url":null,"abstract":"<div><p>Neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Schizophrenia (SCZ), and epilepsy pose a significant global health challenge, particularly among the ageing population. With Alzheimer’s cases projected to double in the next 30 years, the lack of effective treatments presents a critical concern, leading to substantial social and economic burdens. While rodent models have been instrumental in elucidating disease mechanisms and identifying therapeutic targets, their limited translational success necessitates exploring alternative model systems. This review highlights the increasing integration of non-rodent models, including invertebrates (<i>Drosophila melanogaster</i> and <i>Caenorhabditis elegans</i>), lower vertebrates (<i>Danio rerio</i>), and higher-order mammals (non-human primates), alongside emerging approaches such as <i>Octopus</i> models, 2D and 3D cell culture systems, computational models, and in silico methodologies. These alternative models provide unique advantages in studying neural development, function, and pathology, offering improved translational relevance. By leveraging the complementary strengths of these systems, researchers can refine therapeutic strategies and advance our understanding of complex neurological disorders.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145385587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA MYL2 Acts as a Sponge for miR-661 to Regulate Postoperative Cognitive Dysfunction","authors":"Yiguo Xu,&nbsp;Xiaoyun He,&nbsp;Huijun Zhang,&nbsp;Xiuqing Wu,&nbsp;Hongbao Li,&nbsp;Fang Cao","doi":"10.1007/s12031-025-02427-3","DOIUrl":"10.1007/s12031-025-02427-3","url":null,"abstract":"<div><p>Postoperative cognitive dysfunction (POCD) has a significant impact on the postoperative life ability of the elderly, and nearly 50% of the elderly are at risk globally, but the molecular mechanism of its pathogenesis is still unclear. The aim of this study was to discuss the expression of lncRNA MYL2 in older rats and its effects to provide possible targets for future treatment. A POCD model of aged rats was established by osteotomy and sevoflurane, cognitive function was measured by the water maze (MWM), and the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and oxidative stress–related factors in the hippocampal tissue of rats were detected by enzyme-linked immunosorbent assay. Luciferase reporter gene analysis was used to detect the target gene of the targeting relationship between MYL2 and miR-661. Cell viability and apoptosis rate were assessed using CCK-8 and flow cytometry. MYL2 was up-regulated by Sev treatment in the rat hippocampus. Overexpression of MYL2 prolonged the escape latency of rats, shortened the time spent in the target quadrant of rats, and reduced the number of platform crossings. At the same time, the concentrations of pro-inflammatory factors and markers of oxidative stress were increased. miR-661 is a miRNA targeting MYL2. miR-661 could reverse the exacerbation effect of MYL2 on POCD. MYL2 serves as a potential sponge of miR-661, and its up-regulation is linked to exacerbated neuroinflammation, oxidative damage, and cellular dysfunction in POCD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Piperine Prevents Scopolamine-Induced Cognitive Impairment via its Antioxidant and Anti-Inflammatory Roles; Suggesting Potential Modulation of Necroptosis-Related Genes Including MLKL and TNF-α","authors":"Tayebeh Azramezani Kopi,&nbsp;Farzane Shanehbandpour-Tabari,&nbsp;Reyhaneh Mahbubi Arani,&nbsp;Amin Ataie,&nbsp;Mahdi Pouramir,&nbsp;Hossein Khaleghzadeh-Ahangar","doi":"10.1007/s12031-025-02437-1","DOIUrl":"10.1007/s12031-025-02437-1","url":null,"abstract":"<div><p>Alzheimer's disease (AD) is the leading cause of dementia, characterized by cognitive decline and neurodegeneration. Given the limitations of current treatments, research has turned to natural substances such as piperine, which is known for its neuroprotective properties. This study investigates the effects of piperine on cognitive function and genes associated with oxidative stress, inflammation, and necroptosis-related genes in a rat model of cognitive impairment. Fifty adult male Wistar rats were used, divided into five groups: an intact group, a control group (vehicle solution followed by scopolamine), and three experimental groups receiving piperine (5, 10, and 20 mg/kg) followed by scopolamine during the training period. Behavioral assessment was conducted using the Morris Water Maze (MWM) test. Hippocampal tissue was collected after euthanasia for gene expression analysis of Nrf2, HO‑1, TNF‑α, Fas, TRAIL, MLKL, and Caspase‑8. Spatial learning and memory improved significantly in piperine-treated groups, with no impact on swimming velocity, indicating cognitive enhancement without affecting motor functions in the scopolamine-induced cognitive impairment model. Piperine pretreatment prevented oxidative stress and inflammation, as evidenced by the restoration of Nrf2, HO-1, and Caspase-8 and the reduction of TNF-α, Fas, TRAIL, and MLKL expression levels. These findings suggest that piperine has antioxidative, anti‑inflammatory, and cognitive‑enhancing effects, with particular effects possibly on necroptosis, and could be a valuable addition to the current AD treatment paradigm, warranting further investigation in clinical trials.\u0000</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145335971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Causal Relationship Between Palmitoylation Genes and Parkinson’s Disease: A Mendelian Randomization Study","authors":"Jin Qiu,&nbsp;Jiali Yang,&nbsp;Ruisen Zhu,&nbsp;DeHai Xian,&nbsp;Kaiwen Yang","doi":"10.1007/s12031-025-02436-2","DOIUrl":"10.1007/s12031-025-02436-2","url":null,"abstract":"<div><p>This work examined the causal link between palmitoylation-related genes and Parkinson’s disease (PD) by Mendelian randomization (MR). We conducted two-sample Mendelian randomization utilizing genome-wide association study (GWAS) summary statistics. Expression quantitative trait loci (eQTL) data for palmitoylation genes were sourced from eQTLGen, whilst PD data were derived from the GWAS Catalogue (15,056 cases, 12,637 controls) and FinnGen (4,681 cases, 407,500 controls). Instrumental variables (p &lt; 5 × 10⁻⁶, r² &lt; 0.1) were examined using inverse-variance weighted (IVW) regression, along with weighted median, MR-Egger, and Summary-data-based MR (SMR) methods. Sensitivity analyses evaluated pleiotropy and resilience. The IVW analysis revealed significant correlations with Parkinson’s disease for ZDHHC14 (OR = 1.09, <i>P</i> = 0.037), ZDHHC17 (OR = 1.18, <i>P</i> = 0.002), ZDHHC2 (OR = 1.16, <i>P</i> = 0.039), ZDHHC20 (OR = 0.82, <i>P</i> = 0.019), and ZDHHC8 (OR = 1.24, <i>P</i> = 0.022). SMR validation corroborated solely ZDHHC8 (OR = 1.35, <i>P</i> = 0.040). Replication in FinnGen corroborated ZDHHC1, ZDHHC13, ZDHHC17, and ZDHHC8. No heterogeneity or pleiotropy was observed (<i>P</i> &gt; 0.05). ZDHHC8 has a strong causative relationship with PD, suggesting that palmitoylation dysregulation plays a role in disease etiology. These findings underscore synaptic dysfunction as a viable therapeutic target.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Genetic Diversity of DRD2 and OXTR Genes in the Iranian Population and Its Relationship with Personality Traits","authors":"Zahra Sepehri Nader,&nbsp;Shirin Jalili,&nbsp;Fereshteh Rahmati","doi":"10.1007/s12031-025-02430-8","DOIUrl":"10.1007/s12031-025-02430-8","url":null,"abstract":"<div><p>By analyzing genetic polymorphisms in the genes of patients and control subjects, it is possible to find the correlation of these factors with the phenotypic variation as mental disorders to propose hypotheses about the possible mechanisms of specific diseases. Accordingly, in the present study, the role of oxytocin receptor and dopamine D2 receptor polymorphisms in the personality traits of optimistic, pessimistic and intermediate individuals was investigated. In this study, the polymorphism of DRD2 receptors and oxytocin receptor genes in saliva samples of Iranian volunteers was investigated. Accordingly, saliva samples were prepared from 90 individuals. The mental status of these individuals (optimistic, pessimistic and intermediate) was determined by a specialist physician. Then, the DNA of the sample was extracted and the presence or absence of the rs53576 polymorphism in the OXTR gene and the rs1800497 polymorphism in the DRD2 gene was examined using PCR reaction and sequencing. The results showed a significant association between the frequency of the rs53576 polymorphism in the OXTR gene and pessimism. In fact, the A allele in this polymorphism caused a 2.4-fold increase in pessimism in the studied individuals. However, no significant association was observed between the rs1800497 polymorphism and the traits of optimism and pessimism. Such studies require more detailed assessments such as brain scans, but due to the high cost of such tests, genetic studies can be used as the first step to confirm or reject the association of the polymorphism with the aforementioned trait.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145316481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}