IBRO Neuroscience ReportsPub Date : 2025-12-01Epub Date: 2025-07-19DOI: 10.1016/j.ibneur.2025.07.008
Mengzhi Liu , Yuqian Chen , Xinyan Fan , Jinmin Gu , Shihui Xing
{"title":"Beclin1-mediated vascular autophagy negatively regulates angiogenesis and secondary neural damage in the thalamus following cerebral cortical infarction","authors":"Mengzhi Liu , Yuqian Chen , Xinyan Fan , Jinmin Gu , Shihui Xing","doi":"10.1016/j.ibneur.2025.07.008","DOIUrl":"10.1016/j.ibneur.2025.07.008","url":null,"abstract":"<div><div>Focal cerebral infarction induces angiogenesis in the thalamus, which influences cognitive recovery. However, the mechanisms of angiogenesis in the thalamus remain unclear. This study was designed to investigate the potential role of Beclin1-mediated vascular autophagy in angiogenesis occurring in the thalamus after cerebral infarction. Cerebral infarction was induced by middle cerebral artery occlusion (MCAO). Cognitive function was evaluated using the Morris Water Maze. We assessed secondary neuronal damage, angiogenesis, Beclin1 expression and vascular autophagy in blood vessels of the ipsilateral thalamus. The functional effects of Beclin1 on vascular autophagy, angiogenesis and angiogenesis-related factors were determined using lentiviral-delivered siRNA. The results revealed significant angiogenesis in the ipsilateral thalamus at 7 days after MCAO, concurrent with elevated LC3-I to LC3-II conversion and increased Beclin1 expression in the ipsilateral thalamic vessels. Knockdown of Beclin1 markedly suppressed vascular autophagic activation and potentiated thalamic angiogenesis at the above time point. This enhanced angiogenesis correlated with significant reductions of neuronal loss and astrogliosis in the ipsilateral thalamus, alongside improved cognitive function. Furthermore, Beclin1 knockdown significantly increased the levels of angiopoietin-2 (ANG-2) and vascular endothelial growth factor (VEGF) in the ipsilateral thalamus after cerebral infarction. Collectively, these findings implicate that inhibition of Beclin1-mediated vascular autophagy enhances angiogenesis and mitigates secondary thalamic neuronal damage following cerebral infarction. This neuroprotective effect likely related to the restoration of ANG-2 and VEGF levels mediated by vascular autophagy in the thalamus.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 290-299"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144680317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IBRO Neuroscience ReportsPub Date : 2025-12-01Epub Date: 2025-09-02DOI: 10.1016/j.ibneur.2025.08.020
Dean Oldham , Anthony Saviola , Enrique Alvarez , Kimberley D. Bruce
{"title":"Proteomic analysis of cerebrospinal fluid from females with multiple sclerosis highlights elevated microglial function and impaired neurogenesis","authors":"Dean Oldham , Anthony Saviola , Enrique Alvarez , Kimberley D. Bruce","doi":"10.1016/j.ibneur.2025.08.020","DOIUrl":"10.1016/j.ibneur.2025.08.020","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) that is characterized by demyelination, inflammation, and neurological damage. MS is the most common neurological disorder of young adults, negatively impacting their quality of life. Recent population-based estimates have determined that the prevalence of MS in the United States is growing and can be up to 3 times higher in females. While the etiology of MS is complex, involving genetics, immune dysregulation, and environmental triggers, the factors elevating MS risk in women are relatively unexplored. Hence, there is a major need for studies that further our understanding of the pathophysiology of MS in women and identify potential biomarkers and therapeutic targets. To this end, we used highly sensitive and untargeted liquid chromatography-mass spectrometry (LC-MS) to identify proteins in the cerebrospinal fluid (CSF) of age-matched females who were either diagnosed with MS or headache (HA). We found that the CSF of female individuals with MS was enriched in proteins involved in macrophage and microglia function yet depleted in proteins involved in neurogenesis and neuronal function. Overall, our findings support recently identified therapeutic targets (e.g., FABP5), as well as highlighting potential targets that may predict or promote MS neuropathogenesis in females (e.g., CD99, APOC3), which should be studied in larger cohorts going forward.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 624-631"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IBRO Neuroscience ReportsPub Date : 2025-12-01Epub Date: 2025-09-19DOI: 10.1016/j.ibneur.2025.09.005
Leonid S. Godlevsky , Işınsu Alkan , Kıymet Kübra Tüfekci , Mykhailo P. Pervak , Süleyman Kaplan
{"title":"Different mechanisms of axitinib and diazepam antiseizure action in pentylenetetrazol-induced kindling model","authors":"Leonid S. Godlevsky , Işınsu Alkan , Kıymet Kübra Tüfekci , Mykhailo P. Pervak , Süleyman Kaplan","doi":"10.1016/j.ibneur.2025.09.005","DOIUrl":"10.1016/j.ibneur.2025.09.005","url":null,"abstract":"<div><h3>Introduction</h3><div>This study intended to assess the histomorphology characteristics of hippocampal structures and determine the severity of seizures after treatment with the tyrosine kinase B inhibitor axitinib and diazepam in fully developed and postponed period in PTZ-kindled rats.</div></div><div><h3>Methods and materials</h3><div>Wistar rats were given PTZ for 21 days until fully developed convulsions were achieved. Two protocols were explored: assessment of seizures immediately after the completion of the kindling (early kindling) and after a two-week post-kindling PTZ-free period. Treatment with axitinib and diazepam was performed before early and postponed kindling seizures assessment, with the consequent collection of brains for histomorphology.</div></div><div><h3>Results</h3><div>Axitinib and diazepam effectively reduced seizure severity at the early and postponed periods of kindling. Axitinib's antiseizure effectiveness was reduced in the postponed stage of kindling period compared with the early one (P = 0.039), while diazepam's effectiveness was maintained at a similar level (P > 0.05). Stereological quantification of neuronal hippocampus changes revealed an increase in the total volume of the stratum radiatum, while a decrease of the dentate gyrus, in postponed compared with early kindling (P < 0.05). The positivity of collagen type IV, which is present in the blood-brain barrier, increased and was more pronounced in the postponed period in hippocampal structures (CA1-CA3).</div></div><div><h3>Conclusion</h3><div>The antiseizure effect of tyrosine kinase B inhibition with a specific antagonist of VEGF axitinib is particularly pronounced in the early phase of PTZ kindling. Opposite to axitinib, diazepam demonstrated a similar antiseizure action in both periods of kindling. These results suggest a more pronounced contribution of angiogenesis compared with the neuronal degenerative hippocampal damage to the development of PTZ-kindled chronic epileptogenesis.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 668-678"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of the combination of melatonin and N-acetylcysteine on the inflammatory response in a rat model of cerebral ischemia","authors":"Pouria Soleimani , Saied Nekoonam , Fariba Zafari , Fatemeh Sabbaghziarani","doi":"10.1016/j.ibneur.2025.06.004","DOIUrl":"10.1016/j.ibneur.2025.06.004","url":null,"abstract":"<div><div>Stroke is the second leading cause of death and long-term damage globally. Inflammation is a significant factor in the onset of ischemic stroke. This study investigated the simultaneous administration of melatonin and N-acetylcysteine (NAC) on inflammation in rat cerebral ischemia. First, 30 male Wistar rats were randomly divided into five groups (n = 6), including the sham group without ischemia, the ischemic group, and the ischemic groups treated with NAC, melatonin, and NAC + melatonin, respectively. To induce ischemia, a silicone-coated monofilament was placed from the common carotid artery towards the middle cerebral artery and stained for 60 min. The rats were treated by administering NAC (50 mg/kg), melatonin (5 mg/kg) and the combination of NAC + melatonin by intraperitoneal injection after ischemia induction. The animals were assessed for sensory-motor activity at 24 and 72 h. Following sacrifice, the rats' brain was dissected to estimate infarct volume after triphenyltetrazolium chloride (TTC) staining. Inflammatory parameters were then analyzed through gene expression analysis using reverse transcription quantitative polymerase chain reaction (RT-qPCR) for nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and nucleotide oligomerization domain (NOD)-like receptor family with pyrin domain 1 and 3 (NLRP1 and NLRP3). The results showed a significant decrease in mRNA expression of the target genes in the rats treated with NAC + melatonin compared to the ischemic group (p < 0.05). The group that received the combined treatment exhibited enhanced sensory-motor function and a reduced brain infarct volume compared to the other groups (p < 0.05). In summary, the combined use of NAC and melatonin has shown promise in enhancing neurobehavioral function and decreasing the volume of cerebral infarction by regulating the inflammatory signaling pathway.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 83-90"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IBRO Neuroscience ReportsPub Date : 2025-12-01Epub Date: 2025-08-05DOI: 10.1016/j.ibneur.2025.07.015
Hong-Xin Jiang , Yong Wang , Jun-Yan Zhang , Hong-Li Zhang , Guo-Xing Ren , Ting-Ting Gao , Shu-Man Han , Lei Cao , Bu-Lang Gao , Wen-Juan Wu
{"title":"Structures of the nerve fiber bundles near the central sulcus on diffusion tensor imaging","authors":"Hong-Xin Jiang , Yong Wang , Jun-Yan Zhang , Hong-Li Zhang , Guo-Xing Ren , Ting-Ting Gao , Shu-Man Han , Lei Cao , Bu-Lang Gao , Wen-Juan Wu","doi":"10.1016/j.ibneur.2025.07.015","DOIUrl":"10.1016/j.ibneur.2025.07.015","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the morphology and spatial relationship of the structure of the nerve fiber bundles near the central sulcus on diffusion tensor imaging (DTI).</div></div><div><h3>Materials and methods</h3><div>One hundred and eleven healthy subjects were enrolled to undergo magnetic resonance imaging (MRI) DTI scanning, including 68 males and 43 females with an age range of 0–106 years (mean 48). The nerve fiber bundles near the central sulcus were reconstructed for observation and analysis on DTI.</div></div><div><h3>Results</h3><div>There are many fiber bundles distributed near the central sulcus, with complex structures, including the corpus callosum, anterior commissure, fornix, superior longitudinal bundle, inferior frontal occipital bundle, corticospinal bundle, cortical cerebellar bundle, arcuate fiber, visual pathway, cortical dentate nucleus bundle, crossed cortical cerebellar bundle, and bridging fibers. The central sulcus is located between the frontal and parietal lobes, with the anterior central gyrus located in the front and the posterior central gyrus in the back. It connects the left and right hemispheres of the brain through the corpus callosum and is widely connected in the brain through different fiber bundles, including the frontal, parietal, occipital and temporal lobes, cerebellum, spinal cord, thalamus, and brainstem. It is closely related to other conduction tracts in the brain. From premature birth to young adulthood (< 45 years old), the corpus callosum gradually developed with increased numbers of nerve fiber bundles which became denser, wider and more extensively connected to surrounding cerebral tissues. However, from young adulthood to older ages (> 60 years old), the nerve fiber bundles of the corpus callosum became increasingly sparser and less connected with surrounding cerebral tissues. With increase of the age from 4 days after birth to the age 45 years, the nerve fibers of the corpus callosum, lateral bundle of the corpus callosum, cortical dentate nucleus bundle and corticospinal tract became denser, wider, and more extensively connected with surrounding tissues.</div></div><div><h3>Conclusion</h3><div>The structures of the nerve fiber bundles near the central sulcus on DTI are complex and widely connected with other brain regions, with important clinical significance.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 749-759"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Electrophysiological analysis of distal, proximal, and dual compression of the median nerve","authors":"Qiongfang Zhang , Yongfeng Liu , Jinhuan Zhang , Yirong Chen , Xingxian Huang , Haibo Yu","doi":"10.1016/j.ibneur.2025.06.010","DOIUrl":"10.1016/j.ibneur.2025.06.010","url":null,"abstract":"<div><h3>Objective</h3><div>Both distal and proximal compression of the median nerve can lead to hand numbness inpatients.This study aimed to dissect the electrophysiological characteristics of median nerve motor fibers inpatients with carpal tunnel syndrome (CTS) caused by distal median nerve compression, C8 - T1 nerve root - type cervical spondylosis (CRS) resulting from proximal median nerve compression, and double - compression syndrome (DCS) with CTS combined with C8 - T1 CRS, so as to verify the double - nerve compression theory, provide evidence-based basis for clinical treatment.</div></div><div><h3>Methods</h3><div>Retrospective analysis of 30 subjects per group (CTS, CRS, DCS, controls) from a neurophysiological database. Parameters included distal motor latency (DML1-wrist, DML2-elbow), compound muscle action potential (CMAP1, CMAP2), wrist-elbow motor conduction velocity (MCV), and F-wave latency.</div></div><div><h3>Results</h3><div>For each indicator, both the CTS group and the DCS group showed statistically significant differences from the normal group. When comparing between the CTS group and the DCS group, there were no statistically significant differences in all data indicators. When comparing the CRS group with the normal group, there were no statistically significant differences in DML1 and DML2, but there were statistically significant differences in the shortest latency of the F wave and the motor conduction velocity (MCV).</div></div><div><h3>Conclusion</h3><div>Double compression does not cause more severe damage to the nerve compared with simple distal compression. Distal compression of the median nerve causes more severe damage to the peripheral nerve than proximal compression. For patients with double compression syndrome, clinical treatment should prioritize the treatment of the distal compression site.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 205-209"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IBRO Neuroscience ReportsPub Date : 2025-12-01Epub Date: 2025-09-25DOI: 10.1016/j.ibneur.2025.09.013
Anping Ouyang , Jun Jiang , Lin Wu , Xinxin Lin , Lingling Wang , Qiutao Yan , Xuqian Diao , Yan Li , Yuanqiang Zhu , Lingli Zeng , Jiaxi Peng , Qianqian Dong , Wei He , Peng Fang
{"title":"Napping restores working memory and brain activation impaired by sleep deprivation","authors":"Anping Ouyang , Jun Jiang , Lin Wu , Xinxin Lin , Lingling Wang , Qiutao Yan , Xuqian Diao , Yan Li , Yuanqiang Zhu , Lingli Zeng , Jiaxi Peng , Qianqian Dong , Wei He , Peng Fang","doi":"10.1016/j.ibneur.2025.09.013","DOIUrl":"10.1016/j.ibneur.2025.09.013","url":null,"abstract":"<div><h3>Background</h3><div>Sleep deprivation (SD) impairs working memory (WM), yet the restorative potential of brief daytime naps remains underexplored. This study examines how naps counteract SD-induced WM deficits through behavioral and neuroimaging mechanisms, focusing on task-positive networks and default mode network (DMN) dynamics.</div></div><div><h3>Method</h3><div>A within-subject fMRI study employed 2-back WM tasks in 50 participants under three conditions: baseline wakefulness, post-30h SD, and post-nap recovery. Behavioral metrics (reaction times, accuracy) and fMRI activation patterns were analyzed using repeated-measures ANOVA and mixed-effects models to assess SD and nap effects.</div></div><div><h3>Result</h3><div>Naps partially restored SD-induced WM declines, improving reaction times and accuracy. Post-SD, reduced activation in the cerebellum, insula, and thalamus (attention/executive regions) rebounded post-nap. SD weakened DMN suppression (middle frontal gyrus, precuneus, superior temporal gyrus), with maximal DMN suppression post-nap. Improved WM performance correlated with reactivated task-positive networks.</div></div><div><h3>Conclusion</h3><div>Daytime naps mitigate SD-related WM deficits by rebalancing task-positive network activation (cerebellum, thalamus) and enhancing DMN suppression. These findings elucidate neurophysiological mechanisms of sleep-cognition interactions, supporting naps as a practical intervention for SD-induced cognitive impairment</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 709-717"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145264865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IBRO Neuroscience ReportsPub Date : 2025-12-01Epub Date: 2025-11-02DOI: 10.1016/j.ibneur.2025.10.022
Frida Stam , Sara Bjurling , Sofia Zelleroth , Sally Badrd'din , Johan Gising , Mats Larhed , Mathias Hallberg , Alfhild Grönbladh
{"title":"The effects of insulin-regulated aminopeptidase inhibition with HA08 on recognition memory acquisition and spatial working memory under reversed circadian conditions in male rats","authors":"Frida Stam , Sara Bjurling , Sofia Zelleroth , Sally Badrd'din , Johan Gising , Mats Larhed , Mathias Hallberg , Alfhild Grönbladh","doi":"10.1016/j.ibneur.2025.10.022","DOIUrl":"10.1016/j.ibneur.2025.10.022","url":null,"abstract":"<div><div>In 1995, a new M1 aminopeptidase member was discovered in fat and muscle cells, the insulin regulated aminopeptidase (IRAP; oxytocinase; placental leucine aminopeptidase). IRAP can be found in glucose transporter type 4 (GLUT4) vesicles and is believed to regulate cellular glucose uptake by mediating trafficking of GLUT4 to the plasma membrane. It is expressed in various tissues, including areas of the brain associated with cognition, and it cleaves multiple endogenous substrates like oxytocin, vasopressin, somatostatin and cholecystokinin-8. In the beginning of the century, IRAP was identified as the receptor of hexapeptide angiotensin IV (AngIV). AngIV and similar ligands binds to the active site of the peptidase, causing inhibition of its enzymatic activity, which is suggested to increase neuropeptide levels and modulate cellular glucose uptake. This mechanism is suggested to improve cognitive functions, and in 1988 the first evidence of Ang IV’s memory enhancing effects was reported. Since then, several animal behaviour models have demonstrated the positive effects of AngIV on memory. One of the most potent synthetic IRAP inhibitors known today is the macrocyclic compound HA08, that we have previously demonstrated to increase dendritic spine density and restore cell viability. To further evaluate the potential of IRAP inhibitor HA08 as a cognitive enhancer, we have examined this macrocycle compound <em>in vivo</em> using male Sprague Dawley rats. The effect of a single acute intracerebroventricular injection with HA08 on recognition memory acquisition and spatial working memory was evaluated by conducting a novel object recognition test and a Y-maze test. The overall results of this study suggest that an acute single dose of HA08 does not influence memory acquisition in the novel object recognition test, nor spatial memory using a Y-maze, in male rats with intact cognitive functions tested under a reversed light-dark cycle.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 854-861"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
IBRO Neuroscience ReportsPub Date : 2025-12-01Epub Date: 2025-11-05DOI: 10.1016/j.ibneur.2025.11.004
Ya-Han Wang , Yao Xie , Peng-Li Ding , Jin-Wen Ge , Le Xie , Da-Hua Wu , Chao Xin
{"title":"Analysis of the potential regulatory mechanism of PIEZO1 in Alzheimer’s disease based on RNA sequencing","authors":"Ya-Han Wang , Yao Xie , Peng-Li Ding , Jin-Wen Ge , Le Xie , Da-Hua Wu , Chao Xin","doi":"10.1016/j.ibneur.2025.11.004","DOIUrl":"10.1016/j.ibneur.2025.11.004","url":null,"abstract":"<div><div>The ion channel protein PIEZO1 regulates complex processes in Alzheimer’s disease (AD). This study explored the regulatory mechanism of PIEZO1 in AD using bioinformatic analysis, aiming to identify AD-associated genes and potential therapeutic strategies. RNA sequencing (RNA-seq) data based on an in vitro model of AD were obtained from the Gene Expression Omnibus (GEO) database, and differential expression analysis was performed using the DESeq2 R package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted on the identified differentially expressed genes (DEGs). Gene set enrichment analysis (GSEA) and principal component analysis (PCA) were also performed on the gene expression data. PCA clustering revealed overall significant differences among the three groups of samples (control, AD, and PF-562271 intervention group). All DEGs in the three sample groups were subjected to k-means hierarchical clustering, revealing four clusters. The matrix antigen plot indicated multiple changes in the average millions of fragments per thousand bases value of each gene among the groups. Functional annotation was performed for the DEGs between the two groups, and GSEA identified both activated and inhibited pathways, distinguishing the groups. Notably, the expression of PIEZO1 was higher in the AD group than in the control group. This study confirmed elevated PIEZO1 expression in astrocyte AD models, which is associated with the regulation of the extracellular matrix, cell–substrate adhesion, synaptic migration, and other related functions and pathways.</div></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"19 ","pages":"Pages 936-946"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}