Journal of Molecular Neuroscience最新文献

{"title":"Dopamine Receptor D2 gene Polymorphisms rs2005313, rs4274224, and rs4938019 in Pakistani Patients with Schizophrenia:a Diagnostic Tool for Schizophrenia","authors":"Ishrat Yaseen,&nbsp;Saleem Ahmad,&nbsp;Muhammad Ghalib,&nbsp;Muhammad Shahbaz Aslam,&nbsp;Rabbia Tariq,&nbsp;Osheen Sajjad,&nbsp;Faisal Yaseen","doi":"10.1007/s12031-026-02582-1","DOIUrl":"10.1007/s12031-026-02582-1","url":null,"abstract":"<div><p>Background: This study was designed to evaluate the genetic association of three specific intronic Single Nucleotide Polymorphisms (SNPs) within the Dopamine Receptor D2 (DRD2) gene—rs2005313, rs4274224, and rs4938019—with schizophrenia susceptibility in a Pakistani population. The primary objective was to identify population-specific biomarkers that could inform early intervention and personalized treatment strategies. Methods: Genotyping was conducted on a matched case-control cohort of 208 participants (104 cases; 104 controls) using High-Resolution Melting (HRM) PCR. Genetic associations were quantified using Odds Ratios (OR) and 95% Confidence Intervals (CI), representing the standard coefficient and its margin of error to ensure statistical precision. Functional annotation of the investigated polymorphisms was performed using GTEx, FORGEdb and RegulomeDB to assess regulatory potential and tissue-specific expression effects. Results: The research identified highly significant associations across multiple inheritance models, validating the technical robustness of the findings. The rs4938019 polymorphism emerged as the most potent genetic risk factor, particularly under the recessive model (OR: 9.60; 95% CI: 3.92–23.52; p &lt; 0.0001), where the rare GG genotype was found in 44% of cases compared to only 7.2% of controls. Conversely, rs4274224 demonstrated a significant protective effect, with a co-dominant OR of 0.23 (95% CI: 0.09–0.59; p = 0.0022), suggesting that the T allele confers genetic resilience. Furthermore, among the investigated DRD2 variants, rs2005313 demonstrated significance primarily under the over-dominant inheritance model, whereas rs4938019 exhibited the strongest association under the recessive model (OR: 2.13; 95% CI: 1.15–3.94; p = 0.014). All variants in the control group maintained Hardy-Weinberg Equilibrium (p &gt; 0.05), confirming the absence of population bias. Functional annotation revealed that rs4274224 showed the strongest direct regulatory evidence for DRD2 (FORGEdb score: 6; RegulomeDB Rank 1f), while rs4938019 demonstrated the highest overall regulatory potential (FORGEdb score: 9), with rs2005313 exhibiting substantial regulatory evidence (FORGEdb score: 7) supported by extensive GTEx cis-eQTLs across multiple tissues including brain regions. Conclusion: These findings establish DRD2 intronic polymorphisms as critical determinants of schizophrenia risk. The high-risk rs4938019 GG genotype provides a clear translational biomarker for rapid genetic screening, potentially improving clinical outcomes through genotype-guided therapeutic interventions.</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":"76 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676635","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":"Mitochondrial Permeability Transition Regulators As Emerging Therapeutic Targets in Aging and Neurodegeneration: Recent Insights","authors":"Lishu Guo","doi":"10.1007/s12031-026-02583-0","DOIUrl":"10.1007/s12031-026-02583-0","url":null,"abstract":"<div><p>Aging is characterized by increased reactive oxygen species (ROS) and leads to mitochondrial dysfunction. This age-related decline in mitochondrial function is a major factor in the development of neurodegenerative diseases. Mitochondrial permeability transition pore (PTP) is a multi-protein complex that forms a non-specific channel across the inner mitochondrial membrane, and its opening is tightly linked to mitochondrial function and cell death. Dysregulation of PTP opening is now recognized as a central pathogenic mechanism in both normal aging and age-associated neurodegenerative diseases. This review integrates current understanding of mitochondrial permeability transition with emerging evidence implicating three novel regulatory components: F-ATP synthase inhibitory factor 1 (IF1), subunit j of F-ATP synthase, and mitochondrial carrier homolog 2 (MTCH2), expanding the therapeutic landscape for treating aging and neurodegeneration through targeting the PTP.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676741","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":"Kaempferol-Conjugated Manganese Oxide Nanocomposites Mitigate Aluminium Chloride-Induced Neurobehavioral Impairments in a Rat Model of Alzheimer’s disease","authors":"Heng Yu,&nbsp;Xiufeng Liu,&nbsp;Juan Liu,&nbsp;Dong Tang","doi":"10.1007/s12031-026-02571-4","DOIUrl":"10.1007/s12031-026-02571-4","url":null,"abstract":"<div><p>The neurodegenerative illness Alzheimer’s disease (AD) causes cognitive decline. The production of oxidative stress in neurons is thought to play a role in the emergence of AD. The antioxidants, including kaempferol, reduce the course of AD; however, their use is limited by poor bioavailability. Kaempferol-conjugated manganese oxide nanocomposites (KMF@PEG-MnO2 NCs) exhibit enhanced protective effects against AD compared to free kaempferol. In this study, the potential of KMF@PEG-MnO₂ NCs as an anti-Alzheimer’s disease (AD) agent was explored through in silico and experimental approaches. The effective preparation of KMF@PEG-MnO₂ NCs was validated by FT-IR, XRD, DLS, and SEM-EDX characterization techniques. The influence of KMF@PEG-MnO₂ NCs on antioxidant capacity using the DPPH assay, reactive oxygen species (ROS) quantification with the SH-SY5Y cell line, and determining the amyloid β disaggregation was determined. Additionally, blood-brain barrier permeability was assessed with brain endothelial cells, and an anticholinesterase study was performed to explore its potential for treating Alzheimer’s disease. Surface characterization revealed a spherical shape of the nanoparticle. DPPH and FR assay showed a substantial rise in antioxidant defence for KMF@PEG-MnO₂ NCs compared to KMF. Anti-aggregation studies demonstrated the nanoparticle’s ability to inhibit Aβ fibrils. Additionally, the BBB permeability assay indicated that the nanoparticle can permeate the BBB. Furthermore, in vivo studies demonstrated that KMF@PEG-MnO₂ NCs protected against cognitive and synaptic deficits in AlCl₃-induced AD rats (AlCl₃-AD). KMF@PEG-MnO₂ NCs significantly reduced AChE activity. Furthermore, it markedly reduced the brain’s levels of nitric oxide (NO) while increasing the function of superoxide dismutase (SOD) and catalase (CAT) activities. Overall, the findings suggest that KMF@PEG-MnO₂ NCs may serve as a promising therapeutic candidate for AD management.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148667948","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":"PEGylated Liposomal Resveratrol Induces Region-Specific Redox Modulation Without Behavioral or Neurotrophin Recovery in a VPA Model of Autism","authors":"Victória Linden de Rezende,&nbsp;Maria Fernanda Pedro Ebs,&nbsp;Flávia da Silva Daros,&nbsp;Maiara de Aguiar da Costa,&nbsp;Sofia Januário Bolan,&nbsp;Germano Lapa Viana,&nbsp;Leonardo Pelegrini,&nbsp;Nathan de Souza Colonetti,&nbsp;Maria Júlia Ferro Spillere,&nbsp;Giseli da Silva Souza,&nbsp;Rafaela de Sousa Anastácio,&nbsp;Ellen De-Pieri,&nbsp;Júlio César Claudino dos Santos,&nbsp;Ricardo Andrez Machado de Ávila,&nbsp;Alexandre Gonçalves Dal-Bó,&nbsp;Cinara Ludvig Gonçalves","doi":"10.1007/s12031-026-02574-1","DOIUrl":"10.1007/s12031-026-02574-1","url":null,"abstract":"<div><p>Autism Spectrum Disorder (ASD) is associated with neuroinflammation and oxidative stress that disrupt neurodevelopmental processes. Resveratrol (RSV) is a polyphenol with antioxidant and anti-inflammatory properties, but its poor bioavailability limits therapeutic use. This study investigated whether PEGylated liposomes encapsulating RSV (LipRSV) could modulate oxidative and behavioral alterations in a valproic acid (VPA)-induced rat model of ASD. PEGylated LipRSV were synthesized, characterized as hemocompatible, and administered to offspring from postnatal day (PND) 6 to 27. Behavioral tests included developmental milestones, olfactory discrimination, negative geotaxis, open field, and three-chamber social interaction. Oxidative stress markers and neurotrophins (BDNF, NGF) were quantified in the following brain regions: hippocampus, hypothalamus, striatum, cerebellum, frontal and posterior cortex. LipRSV exerted limited and region-dependent redox effects, reducing ROS levels only in the hippocampus, cerebellum, and posterior cortex, while failing to improve behavioral outcomes and being associated with unfavorable neurochemical alterations, including reduced BDNF and NGF levels. Importantly, LipRSV also induced behavioral deficits, redox imbalance, and neurochemical alterations in control animals, indicating treatment-related effects in the absence of VPA exposure. LipRSV modulated oxidative stress in a region-dependent manner without improving behavioral deficits in the VPA model and was associated with reduced BDNF and NGF levels. This study provides evidence that modulation of oxidative stress alone is insufficient to rescue behavioral phenotypes in the VPA model of ASD. These findings highlight the partial neurochemical efficacy and translational limitations of this formulation, suggesting the need for optimized nanocarrier design and dosing strategies in ASD pharmacotherapy.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148652760","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":"Peroxisome Proliferator-Activated Receptor Delta (PPARδ) as a Metabolic Gatekeeper of Cerebrovascular Integrity","authors":"Shuhei Shiino,&nbsp;Crissey Pascale,&nbsp;Khashaiar Motazedian,&nbsp;Emma Lesser,&nbsp;Aaron Dumont,&nbsp;Alejandra N. Martinez","doi":"10.1007/s12031-026-02576-z","DOIUrl":"10.1007/s12031-026-02576-z","url":null,"abstract":"<div><p>The peroxisome proliferator-activated receptor delta (PPARδ) is a nuclear receptor highly expressed in vasculature and serves a central role in coordinating vascular and metabolic homeostasis across multiple physiological systems. Recent studies have highlighted PPARδ’s remarkable ability to regulate endothelial fatty acid oxidation, enhance metabolic flexibility, and modulate angiogenic responses critical for vascular adaptation and repair. Beyond its metabolic functions, PPARδ orchestrates multiple protective pathways that preserve cerebrovascular homeostasis, including endothelial repair, maintenance of blood-brain barrier integrity, mitochondrial biogenesis, and stability of the neurovascular unit, collectively enhancing endothelial resilience to stress. Dysregulation of PPARδ signaling has been implicated in various vascular and neurodegenerative disease states, underscoring its clinical relevance. In this literature review, we synthesize current findings on PPARδ-mediated signaling pathways and evaluate its potential as a promising therapeutic target. We further explore mechanistic roles across pathological contexts, as well as discuss emerging translational strategies aimed at harnessing PPARδ modulation for vascular and neuroprotective therapies.</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":"76 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-026-02576-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148614801","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":"Maternal Traumatic Brain Injury Increases Fetal Brain Cis p-tau Levels: Evidence for Potential Transplacental Effects in a Murine Model","authors":"Maryam Asgari,&nbsp;Seyyedeh Elaheh Mousavi,&nbsp;Davood Zaeifi,&nbsp;Ehsan Ehsani","doi":"10.1007/s12031-026-02580-3","DOIUrl":"10.1007/s12031-026-02580-3","url":null,"abstract":"<div><p>Traumatic brain injury (TBI) is a well-established risk factor for Alzheimer’s disease-related tauopathy. However, whether maternal TBI can lead to transgenerational transmission of pathogenic tau to offspring remains unknown. This study examines whether maternal Traumatic brain injury (TBI) induces pathogenic tau transfer to offspring, impairing fetal brain development. TBI was induced in pregnant Balb/C mice prior to pregnancy using a weight-drop model, while the sham group underwent anesthesia without injury, and the fetal brains were analyzed for cis p-tau using immunofluorescence (IF) and Western blotting (WB). Maternal anxiety post-TBI was assessed via the Elevated Plus Maze (EPM). Compared with the sham group, maternal TBI resulted in 4.25 and 5.81-fold increase in cis p-tau aggregation in embryonic and fetal brains, respectively (F(2,12) = 68.45, <i>p</i> &lt; 0.001; F(2,12) = 102.34, <i>p</i> &lt; 0.0001), and protein levels showed 3.13- and 6.79-fold increases (F(2,12) = 45.12, <i>p</i> &lt; 0.001; F(2,12) = 89.67, <i>p</i> &lt; 0.0001). This was accompanied by a significant increase in apparent transfer efficiency of p-tau to fetal brains (t(8) = 12.50, <i>p</i> &lt; 0.0001). EPM assessment revealed that TBI-induced dams spent significantly more time in the open arms compared with sham (t(8) = 2.65, <i>p</i> = 0.029), suggesting reduced anxiety-like behavior or increased risk-taking. Maternal serum p-tau181 and fetal cis p-tau showed a positive but non-significant correlation (r(3) = 0.78, <i>p</i> = 0.120). These changes were associated with IL-6 and TNF increased by 2.8-fold (t(8) = 4.22, <i>p</i> = 0.003) and 1.8-fold (t(8) = 2.45, <i>p</i> = 0.040), respectively. These findings demonstrate a significant increase in apparent p-tau transfer efficiency from maternal serum to fetal brain following maternal TBI, although the correlation between maternal serum p-tau181 and fetal brain cis p-tau did not reach statistical significance.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>Maternal TBI may enhance the transfer of p-tau to the fetal brain in mice. Maternal traumatic brain injury in pregnant mice leads to significantly elevated cis p-tau levels in embryonic and fetal brains, accompanied by systemic inflammation, which provides evidence for potential transplacental tau transmission</p></div></div></figure></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148614763","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":"Environmental enrichment applied during epileptogenesis increases seizure latency and reduces serum interleukin-6 in a PTZ kindling model","authors":"Ana Carolina Sulzbach,&nbsp;Gabriel de Lima Rosa,&nbsp;Laura Gentilin Grotto,&nbsp;Rafael Bremm Padilha,&nbsp;Amanda Muliterno Domingues Lourenço de Lima,&nbsp;Edson Fernando Muller Guzzo,&nbsp;Brayan Braz Barbosa,&nbsp;Tainá Schons,&nbsp;Rosa Maria Martins de Almeida,&nbsp;Adriana Simon Coitinho","doi":"10.1007/s12031-026-02567-0","DOIUrl":"10.1007/s12031-026-02567-0","url":null,"abstract":"<div><p>Epilepsy is a chronic neurological disorder affecting millions of individuals worldwide and is strongly associated with inflammatory processes. Although pharmacological treatment remains the first-line approach, approximately one-third of patients are refractory to available therapies. Environmental enrichment (EE) has been shown to improve cognitive function, reduce stress, and enhance neuroplasticity, suggesting its potential as a non-pharmacological strategy for neurological disorders.</p><p>In this study, we investigated the effects of EE in a pentylenetetrazole (PTZ)-induced seizure model using different exposure paradigms. Animals were exposed either to EE for 30 days prior to seizure induction or during the 14-day PTZ kindling protocol. Seizure severity and latency were assessed, along with inflammatory (interleukin-6) and stress-related (cortisol) biomarkers.</p><p>EE exposure during seizure induction significantly increased the latency to seizure onset compared to both the control and pre-exposed groups, with a significant Group × Session interaction across the kindling protocol and pronounced effects at later PTZ sessions. A borderline trend toward reduced seizure severity was also observed in this group, but day-specific differences did not survive correction for multiple comparisons. The EED group also exhibited significantly lower serum IL-6 levels compared with controls. No significant differences in cortisol levels were observed in serum or in the frontal cortex. Pre-exposure to EE did not produce significant protective effects on any of the outcomes evaluated.</p><p>These findings suggest that EE exerts beneficial effects when applied during epileptogenic processes, particularly on the temporal progression of seizure susceptibility, and may be associated with changes in selected inflammatory markers. EE may represent a promising adjunct therapeutic strategy for epilepsy, although mechanistic studies with broader molecular characterization are still needed.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13388640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547468","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":"Clinical and Genetic Insights into Angelman Syndrome: A Retrospective Study of 26 Cases in Morocco","authors":"Amal Ouskri,&nbsp;Bouramtane Abdelhamid,&nbsp;Daha Belghiti Hanae,&nbsp;Ahakoud Mohammed,&nbsp;Bouguenouch Laila,&nbsp;Ouldim Karim","doi":"10.1007/s12031-026-02570-5","DOIUrl":"10.1007/s12031-026-02570-5","url":null,"abstract":"<div><p>Angelman syndrome (OMIM #105830) is a rare neurodevelopmental disorder caused by loss of function of the maternally inherited <i>UBE3A</i> gene within the imprinted 15q11.2–q13 region. Although its clinical and molecular characteristics have been well described in European and Asian populations, data from low- and middle-income countries remain scarce. This retrospective study aimed to characterize the clinical and molecular features of Angelman syndrome in a Moroccan cohort and investigate genotype–phenotype correlations. Twenty-six patients with molecularly confirmed Angelman syndrome diagnosed between 2018 and 2022 at the Department of Medical Genetics, Hassan II University Hospital, Fez, were included. Molecular diagnosis was established using methylation-specific PCR, fluorescence in situ hybridization, and UBE3A sequencing. The cohort showed a female predominance (61.5%) and a median age at diagnosis of 5.7 years, indicating delayed diagnosis. Core clinical features included intellectual disability (100%), absent speech (96%), seizures (87%), Angelman syndrome-specific EEG abnormalities (87%), ataxia (87%), and hypersalivation (92%). Molecular analyses identified 15q11.2–q13 deletions in 77% of patients, imprinting defects or uniparental disomy in 11.5%, and UBE3A variants in 11.5%. Patients with maternal deletions exhibited a more severe neurological phenotype. This study, the largest Moroccan cohort of Angelman syndrome, highlights delayed diagnosis and limited access to molecular testing. Although hypersalivation was frequently observed, this finding should be interpreted cautiously, as it may reflect severe oromotor dysfunction and impaired swallowing rather than increased salivary secretion. These findings support earlier recognition, comprehensive molecular diagnosis, and improved access to genetic services in resource-limited settings. </p><p>Clinical trial number: Not applicable.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148519783","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":"Integrated Bioinformatics and Network Analysis Identifies Key Molecular Targets and Hub Genes in Zika Virus-induced Neuroinflammation","authors":"Akmal Zubair,&nbsp;Muhammad Ali,&nbsp;Adel Qlayel Alkhedaide","doi":"10.1007/s12031-026-02572-3","DOIUrl":"10.1007/s12031-026-02572-3","url":null,"abstract":"<div><p>The Zika virus (ZIKV) infection has shown significant neurodevelopmental and neurological abnormalities. However, the molecular mechanisms of ZIKV-induced neuroinflammation are poorly understood. In the current study, an integrative approach of bioinformatics analysis was used to identify the molecular targets involved in the ZIKV infection. Microarray data sets consisting of 65 samples (35 ZIKV-positive and 30 controls) from the Gene Expression Omnibus (GEO) database were used for the study. The differentially expressed genes (DEGs) analysis revealed 1,268 differentially expressed genes, of which 505 genes were up-regulated, while 763 genes were found to be down-regulated. The analysis using the weighted gene co-expression network analysis (WGCNA) revealed two modules that showed significant correlation with the ZIKV-positive samples. A total of 535 overlapping genes were used for further analysis. The protein-protein interaction (PPI) network analysis revealed ten hub genes: ITGAM, CD86, PTPRC, FCGR3A, ITGB2, TNF, ITGAX, CSF1R, CCR5, and CD4. This study suggests that the immune response plays an important role in the ZIKV infection. The study also revealed a significant enrichment of genes associated with neurogenesis, synaptic organization, axon guidance, immune response and amyloid beta binding by performing gene ontology (GO) analysis. This data potentially indicates that ZIKV infection can modulate these key hub genes to cause neuroinflammation. In addition, the study also revealed that the ZIKV infection can regulate various transcription factors and microRNAs that regulate these hub genes, indicating the complex regulatory mechanism of the ZIKV infection. Furthermore, the study revealed that the receiver operating characteristic (ROC) curve analysis showed that these hub genes, especially CCR5, are of preliminary diagnostic potential value. The study provided new insights into the molecular mechanisms of ZIKV-induced neuroinflammation and revealed the potential biomarkers and therapeutic targets of ZIKV-induced neurological disorders.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148519820","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":"Integrated Expression and Bioinformatic Analysis of AKT-Associated lncRNAs Suggests UCA1 as a Candidate Biomarker for Bipolar Disorder","authors":"Mohammad Kazem Tavakoli,&nbsp;Mohammad Javad Mokhtari","doi":"10.1007/s12031-026-02575-0","DOIUrl":"10.1007/s12031-026-02575-0","url":null,"abstract":"<div><p>Bipolar disorder (BD) is a severe psychiatric disorder characterized by recurrent disturbances in mood and behavior. Given the reported involvement of the AKT signaling pathway in BD, we investigated the expression of three AKT-associated long non-coding RNAs (LINC-ROR, MALAT1, and UCA1) in peripheral blood samples from patients with BD and healthy controls. Furthermore, we performed exploratory bioinformatic analyses to identify potential lncRNA-miRNA and lncRNA–RNA-binding protein interaction networks. In the present study, we evaluated the expression profiles of three AKT signaling pathway-associated lncRNAs, namely LINC-ROR, MALAT1, and UCA1, in peripheral blood samples from patients with BD. We compared these findings with those from healthy control subjects. Additionally, an <i>in silico</i> analysis was performed to investigate potential microRNA (miRNA) binding sites within these lncRNAs and to assess their interactions with RNA-binding proteins (RBPs), thereby providing further insight into their potential regulatory roles in BD pathogenesis. MALAT1 and UCA1 expression levels were significantly higher in patients with BD than in healthy controls. Although LINC-ROR expression showed a trend toward downregulation, the difference did not remain statistically significant after Bonferroni correction for multiple comparisons. Among the investigated lncRNAs, UCA1 exhibited the strongest discriminatory performance in differentiating individuals with BD from control subjects, achieving an area under the receiver operating characteristic curve (AUC) of 0.75 (<i>P</i> &lt; 0.0001, 95% CI: 65%–84%). Previous evidence demonstrating the involvement of the AKT signaling pathway in the pathogenesis of BD further supports the hypothesis that dysregulation of pathway-associated lncRNAs contributes to the disorder. These findings support the involvement of AKT-associated lncRNAs in BD pathophysiology and suggest that UCA1 may represent a candidate biomarker requiring further validation in larger independent cohorts.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148519759","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}