Journal of Molecular Neuroscience最新文献

{"title":"Editorial: The Current Categorical Concept of Schizophrenia is Inadequate: Should we Look at the Current State of Affairs for Compensatory Processes?","authors":"Joseph Levine, Illana Gozes","doi":"10.1007/s12031-024-02246-y","DOIUrl":"10.1007/s12031-024-02246-y","url":null,"abstract":"","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632265","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":"Multiple Exposures to Sevoflurane General Anesthesia During Pregnancy Inhibit CaMKII/CREB Axis by Downregulating HCN2 to Induce an Autism-Like Phenotype in Offspring Mice","authors":"Fusheng Wei,&nbsp;Ting Chen,&nbsp;Yuanlu Huang,&nbsp;Yuxuan Yang,&nbsp;Xiaoe Cheng,&nbsp;Lei Yang","doi":"10.1007/s12031-024-02243-1","DOIUrl":"10.1007/s12031-024-02243-1","url":null,"abstract":"<div><p>The objective of this investigation was to examine the impact of multiple exposures to general anesthesia (GA) with sevoflurane on the offspring of pregnant mice, as well as to elucidate the underlying mechanism. Neurodevelopmental assessments, including various reflexes and behavioral tests, were conducted on the offspring in the GA group to evaluate neuronal cell development. Furthermore, neonatal mouse neuronal cells were isolated and transfected with a high-expression CREB vector (pcDNA3.1-CREB), followed by treatment with sevoflurane (0.72 mol/L), ZD7288 (50 μmol/L), and KN-62 (10 μmol/L), or a combination of these compounds. The expression of relevant genes was then analyzed using qRT-PCR and western blot techniques. In comparison to the sham group, neonatal mice in the GA group exhibited significantly prolonged latencies in surface righting reflex, geotaxis test, and air righting reflex. Furthermore, there was a notable deceleration in the development of body weight and tail in the GA group. These mice also displayed impairments in social ability, reduced reciprocal social interaction behaviors, diminished learning capacity, and heightened levels of anxious behaviors. Additionally, synaptic trigger malfunction was observed, along with decreased production of c-Fos and neurotrophic factors. Sevoflurane was found to notably decrease cellular c-Fos and neurotrophic factor production, as well as the expression of HCN2 and CaMKII/CREB-related proteins. The inhibitory effects of sevoflurane on HCN2 or CaMKII channels were similar to those observed with ZD7288 or KN-62 inhibition. However, overexpression of CREB mitigated the impact of sevoflurane on neuronal cells. Repetitive exposure to sevoflurane general anesthesia while pregnant suppresses the CaMKII/CREB pathway, leading to the development of autism-like characteristics in offspring mice through the reduction of HCN2 expression.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625555","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":"Identification of Potential Biomarkers for Patients with DWI-Negative Ischemic Stroke","authors":"Lei Li,&nbsp;Ying Wang","doi":"10.1007/s12031-024-02229-z","DOIUrl":"10.1007/s12031-024-02229-z","url":null,"abstract":"<div><p>Ischemic stroke is the leading cause of long-term disability in adults, accounting for 80% of stroke cases. Diffusion weighted imaging (DWI) examination is the main test for acute ischemic stroke, but in recent years, several studies have shown that some patients show negative DWI examination after the onset of ischemic stroke with symptoms of significant neurological deficits. In this study, we investigated potential biomarkers related to immune metabolism in the peripheral blood of DWI-negative versus DWI-positive patients after ischemic stroke and explored their possible regulatory processes in ischemic stroke. The datasets related to ischemic stroke were downloaded from the GEO database, immune-related genes and metabolism-related genes were obtained from the ImmPort database and MSigDB database, respectively, and immune-related differential genes were obtained based on immune scores using the algorithm of the R software package “GSVA.” Candidate genes were selected based on intersections, hub genes were screened using the algorithm in Cytoscape software, and finally, GeneMANIA analysis, GSEA enrichment analysis, subcellular localization, gene transcription factor and gene-drug interaction networks, and disease correlation analyses were performed for the hub genes. Five hub genes (GART, TYMS, PPAT, CTPS1, and PAICS) were obtained by PPI network analysis and software analysis. Among them, PPAT and PAICS may be the real hub genes with consistent and significantly differentiated results from the discovery and validation sets. The functions of these hub genes may be related to pathways such as nucleotide biosynthetic processes. The constructed hub gene ceRNA network showed that hsa-10a-5p is the key miRNA connecting PAICS and multiple lncRNAs in this study. Differential genes related to immunity and metabolism in DWI-negative and DWI-positive patients after IS were identified using bioinformatics analysis, and their pathways and related TF-RNAs, miRNAs, and lncRNAs were identified. These genes may be considered effective targets for the diagnosis and treatment of ischemic stroke.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589338","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":"Serum Erythropoietin and Ischemic-Modified Albumin Levels in Adolescents with Obsessive–Compulsive Disorder","authors":"Masum Öztürk,&nbsp;Fatma Subaşı Turgut,&nbsp;Davut Akbalık,&nbsp;Mustafa Erhan Demirkıran,&nbsp;İbrahim Kaplan","doi":"10.1007/s12031-024-02247-x","DOIUrl":"10.1007/s12031-024-02247-x","url":null,"abstract":"<div><p>Erythropoietin (EPO) has neuroprotective effects by increasing oxidative stress resistance and stabilizing redox balance. Ischemic-modified albumin (IMA) is a product of protein oxidation, and recent evidence suggests that IMA can be used as an indicator of oxidative damage. This study aimed to investigate serum EPO and IMA levels in obsessive–compulsive disorder (OCD) patients and to investigate the relationship between EPO and IMA levels and clinical variables such as disease duration and disease severity. A total of 68 adolescents (11–18 years old), including 35 OCD patients (18 males/17 females) and 33 healthy controls (14 males/19 females) without comorbid disorders matched for age, gender, and BMI, were included in the study. The enzyme-amplified chemiluminescence technique determined serum EPO levels, and serum IMA levels were determined by the spectrophotometric method. Serum EPO levels were lower in OCD patients compared to healthy controls (<i>p</i> = 0.002; <i>Z</i> =  − 3.123), and serum IMA levels (ABSU) were significantly higher in the OCD group (<i>p</i> = 0.005). A significant positive correlation was found between IMA levels and the duration of OCD symptoms (<i>p</i> = 0.015, <i>r</i> = 0.409). The study’s findings contribute to the growing body of evidence implicating inflammatory and oxidative processes in the pathogenesis of OCD. The potential of EPO and IMA levels as diagnostic biomarkers for OCD aligns with the ongoing efforts to identify reliable biological markers for the disorder. The positive correlation of IMA levels with the duration of OCD shows the importance of early detection of oxidative damage.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589339","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":"Regulation of MicroRNAs After Spinal Cord Injury in Adult Zebrafish","authors":"Wenyuan Shen,&nbsp;Jun Cai,&nbsp;Jinze Li,&nbsp;Wenchang Li,&nbsp;Pengcheng Shi,&nbsp;Xiumei Zhao,&nbsp;Shiqing Feng","doi":"10.1007/s12031-024-02242-2","DOIUrl":"10.1007/s12031-024-02242-2","url":null,"abstract":"<div><p>Spinal cord injury (SCI) is a central nerve injury that often leads to loss of motor and sensory functions at or below the level of the injury. Zebrafish have a strong ability to repair after SCI, but the role of microRNAs (miRNAs) after SCI remains unclear. Locomotor behavior analysis showed that adult zebrafish recovered about 30% of their motor ability at 2 weeks and 55% at 3 weeks after SCI, reflecting their strong ability to repair SCI. Through miRNA sequencing, mRNA sequencing, RT-qPCR experiment verification, and bioinformatics predictive analysis, the key miRNAs and related genes in the repair of SCI were screened. A total of 38 miRNAs were significantly different, the top ten miRNAs were verified by RT-qPCR. The prediction target genes were verified by the mRNAs sequencing results at the same time point. Finally, 182 target genes were identified as likely to be networked regulated by the 38 different miRNAs. GO and KEGG enrichment analysis found that miRNAs targeted gene regulation of many key pathways, such as membrane tissue transport, ribosome function, lipid binding, and peroxidase activity. The PPI network analysis showed that miRNAs were involved in SCI repair through complex network regulation, among which dre-miR-21 may enhance cell reversibility through <i>nop56</i>, and that dre-miR-125c regulates axon growth through <i>kpnb1</i> to repair SCI.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div><p>miRNAs promote neuronal survival and axon growth after SCI. The expression of dre-miR-21 was increased after SCI. Dre-miR-21 targets <i>nop56</i> mRNA, which causes the Nop56 expression level to reduce, thus reducing the nuclei of ribosomal RNA methylation level, increasing the resistance of neurons, and promoting neuronal cell survival. The level of dre-miR-125c is increased after SCI, and dre-miR-125c targets <i>kpnb1</i> mRNA and reduces the concentration of Kpnb1 at the axon site, thereby promoting axon outgrowth. At the same time, Kpnb1 is a retrograde signal protein of nerve injury, and reducing the expression level of Kpnb1 can inhibit cell death caused by excessive stress response.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578652","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":"Exploratory Mass Spectrometry of Cerebrospinal Fluid from Persons with Autopsy-Confirmed LATE-NC","authors":"Jozsef Gal,&nbsp;Calvin Vary,&nbsp;Carlos A. Gartner,&nbsp;Gregory A. Jicha,&nbsp;Erin L. Abner,&nbsp;Yulica S. Ortega,&nbsp;Ibrahim Choucair,&nbsp;Donna M. Wilcock,&nbsp;Ruth S. Nelson,&nbsp;Peter T. Nelson","doi":"10.1007/s12031-024-02239-x","DOIUrl":"10.1007/s12031-024-02239-x","url":null,"abstract":"<div><p>Common neuropathologies associated with dementia include Alzheimer’s disease neuropathologic change (ADNC) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Biofluid proteomics provides a window into the pathobiology of dementia and the information from biofluid tests may help guide clinical management. Participants (<i>n</i> = 29) had been autopsied and had antemortem CSF draws in a longitudinal cohort of older adults at the University of Kentucky AD Research Center. Cases were designated as LATE-NC + if they had LATE-NC stage &gt; 1 (<i>n</i> = 9); the remaining 20 cases were designated LATE-NC-. This convenience sample of CSF specimens was analyzed in two separate processes: From one group, aliquots were depleted of highly abundant proteins using affinity spin columns. Tryptic digests of sample proteins were subjected to liquid chromatographic separation and mass spectrometry. Relative quantification was performed using Sciex software. Peptides referent to a total of 949 proteins were identified in the samples depleted of abundant proteins, and 820 different proteins were identified in the non-depleted samples. When the Bonferroni/false-discovery statistical correction was applied to account for having made multiple comparison tests, only 4 proteins showed differential expression (LATE-NC + vs LATE-NC-) in the non-depleted samples (RBP4, MIF, IGHG3, and ITM2B). Post hoc western blots confirmed that RBP4 expression was higher in the LATE-NC + cases at the group level. In summary, an exploratory assessment of proteomes of autopsy-confirmed LATE-NC and non-LATE-NC CSF did not demonstrate a clear-cut proteomic fingerprint that distinguished the two groups. There was, however, an increase in RBP4 protein levels in CSF from LATE-NC cases.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578632","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":"Investigation of the Circular Transcriptome in Alzheimer’s Disease Brain","authors":"Yulan Gao,&nbsp;Si-Mei Xu,&nbsp;Yuning Cheng,&nbsp;Konii Takenaka,&nbsp;Grace Lindner,&nbsp;Michael Janitz","doi":"10.1007/s12031-024-02236-0","DOIUrl":"10.1007/s12031-024-02236-0","url":null,"abstract":"<div><p>Circular RNAs (circRNAs) are a subclass of non-coding RNAs which have demonstrated potential as biomarkers for Alzheimer’s disease (AD). In this study, we conducted a comprehensive exploration of the circRNA transcriptome within AD brain tissues. Specifically, we assessed circRNA expression patterns in the dorsolateral prefrontal cortex collected from nine AD-afflicted individuals and eight healthy controls. Utilising two circRNA detection tools, CIRI2 and CIRCexplorer2, we detected thousands of circRNAs and performed a differential expression analysis. CircRNAs which exhibited statistically significantly differential expression were identified as AD-specific differentially expressed circRNAs. Notably, our investigation revealed 120 circRNAs with significant upregulation and 1325 circRNAs displaying significant downregulation in AD brains when compared to healthy brain tissue. Additionally, we explored the expression profiles of the linear RNA counterparts corresponding to differentially expressed circRNAs in AD-afflicted brains and discovered that the linear RNA counterparts exhibited no significant changes in the levels of expression. We used CRAFT tool to predict that circUBE4B had potential to target miRNA named as hsa-miR-325-5p, ultimately regulated <i>CD44</i> gene. This study provides a comprehensive overview of differentially expressed circRNAs in the context of AD brains, underscoring their potential as molecular biomarkers for AD. These findings significantly enhance our comprehension of AD’s underlying pathophysiological mechanisms, offering promising avenues for future diagnostic and therapeutic developments.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562338","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":"Characterizing the Linkage of Systemic Hypoxia and Angiogenesis in High-Grade Glioma to Define the Changes in Tumor Microenvironment for Predicting Prognosis","authors":"Richa Shrivastava,&nbsp;Puneet Gandhi,&nbsp;Sandeep K. Sorte,&nbsp;Adesh Shrivastava","doi":"10.1007/s12031-024-02240-4","DOIUrl":"10.1007/s12031-024-02240-4","url":null,"abstract":"<div><p>High-grade gliomas (HGG) comprising WHO grades 3 and 4 have a poor overall survival (OS) that has not improved in the past decade. Herein, markers representing four components of the tumor microenvironment (TME) were identified to define their linked expression in TME and predict the prognosis in HGG, namely, interleukin6 (IL6, inflammation), inducible nitric oxide synthase(iNOS), heat shock protein-70 (HSP70, hypoxia), vascular endothelial growth receptor (VEGF), and endothelin1 (ET1) (angiogenesis) and matrix metalloprotease-14 (MMP14) and intercellular adhesion molecule1 (ICAM1, extracellular matrix). To establish a non-invasive panel of biomarkers for precise prognostication in HGG. Eighty-six therapy-naive HGG patients with 45 controls were analyzed for the defined panel. Systemic expression of extracellular/secretory biomarkers was screened dot-immune assay (DIA), quantified by ELISA, and validated by immunocytochemistry (ICC). Expression of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 was found to be positively associated with grade. Quantification of circulating levels of the markers by ELISA and ICC presented a similar result. The biomarkers were observed to negatively correlate with OS (<i>p</i> &lt; 0.0001). Cox-regression analysis yielded all biomarkers as good prognostic indicators and independent of confounders. On applying combination statistics, the biomarker panel achieved higher sensitivity than single markers to define survival. The intra-association of all seven biomarkers was significant, hinting of a cross-talk between the TME components and a hypoxia driven systemic inflammation upregulating the expression of other components. This is a first ever experimental study of a marker panel that can distinguish between histopathological grades and also delineate differential survival using liquid biopsy, suggesting that markers of hypoxia can be a cornerstone for personalized therapy. The panel of biomarkers of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 holds promise for prognostication in HGG.</p><h3>Graphical Abstract</h3><p>The cross-talk between the systemic biomarkers of four different partakers of tumor microenvironment</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533268","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":"Multiple Roles of Apolipoprotein E4 in Oxidative Lipid Metabolism and Ferroptosis During the Pathogenesis of Alzheimer’s Disease","authors":"Parisa Faraji,&nbsp;Hartmut Kühn,&nbsp;Shahin Ahmadian","doi":"10.1007/s12031-024-02224-4","DOIUrl":"10.1007/s12031-024-02224-4","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide and has a great socio-economic impact. Modified oxidative lipid metabolism and dysregulated iron homeostasis have been implicated in the pathogenesis of this disorder, but the detailed pathophysiological mechanisms still remain unclear. Apolipoprotein E (APOE) is a lipid-binding protein that occurs in large quantities in human blood plasma, and a polymorphism of the <i>APOE</i> gene locus has been identified as risk factors for AD. The human genome involves three major APOE alleles (<i>APOE2</i>, <i>APOE3</i>, <i>APOE4</i>), which encode for three subtly distinct apolipoprotein E isoforms (APOE2, APOE3, APOE4). The canonic function of these apolipoproteins is lipid transport in blood and brain, but <i>APOE4</i> allele carriers have a much higher risk for AD. In fact, about 60% of clinically diagnosed AD patients carry at least one <i>APOE4</i> allele in their genomes. Although the APOE4 protein has been implicated in pathophysiological key processes of AD, such as extracellular beta-amyloid (Aβ) aggregation, mitochondrial dysfunction, neuroinflammation, formation of neurofibrillary tangles, modified oxidative lipid metabolism, and ferroptotic cell death, the underlying molecular mechanisms are still not well understood. As for all mammalian cells, iron plays a crucial role in neuronal functions and dysregulation of iron homeostasis has also been implicated in the pathogenesis of AD. Imbalances in iron homeostasis and impairment of the hydroperoxy lipid-reducing capacity induce cellular dysfunction leading to neuronal ferroptosis. In this review, we summarize the current knowledge on <i>APOE4</i>-related oxidative lipid metabolism and the potential role of ferroptosis in the pathogenesis of AD. Pharmacological interference with these processes might offer innovative strategies for therapeutic interventions.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490434","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":"The Possible Neuroprotective Effect of Caffeic Acid on Cognitive Changes and Anxiety-Like Behavior Occurring in Young Rats Fed on High-Fat Diet and Exposed to Chronic Stress: Role of β-Catenin/GSK-3B Pathway","authors":"Norhan S. El-Sayed,&nbsp;Nehal Adel Khalil,&nbsp;Samar R. Saleh,&nbsp;Rania G. Aly,&nbsp;Marianne Basta","doi":"10.1007/s12031-024-02232-4","DOIUrl":"10.1007/s12031-024-02232-4","url":null,"abstract":"<div><p>Lifestyle influences physical and cognitive development during the period of adolescence greatly. The most important of these lifestyle factors are diet and stress. Therefore, the aim of this study was to investigate the impact of high fat diet (HFD) and chronic mild stress on cognitive function and anxiety-like behaviors in young rats and to study the role of caffeic acid as a potential treatment for anxiety and cognitive dysfunction. Forty rats were assigned into 4 groups: control, HFD, HFD + stress, and caffeic acid-treated group. Rats were sacrificed after neurobehavioral testing. We detected memory impairment and anxiety-like behavior in rats which were more exaggerated in stressed rats. Alongside the behavioral changes, there were biochemical and histological changes. HFD and/or stress decreased hippocampal brain-derived neurotrophic factor (BDNF) levels and induced oxidative and inflammatory changes in the hippocampus. In addition, they suppressed Wnt/β-catenin pathway which was associated with activation of glycogen synthase kinase 3β (GSK3β). HFD and stress increased arginase 1 and inducible nitric oxide synthase (iNOS) levels as well. These disturbances were found to be aggravated in stressed rats than HFD group. However, caffeic acid was able to reverse these deteriorations leading to memory improvement and ameliorating anxiety-like behavior. So, the current study highlights an important neuroprotective role for caffeic acid that may guard against induction of cognitive dysfunction and anxiety disorders in adolescents who are exposed to HFD and/or stress.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490435","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}