Synapse最新文献

{"title":"Resveratrol Improves Fine Motor Performance and Attenuates Oxidative Stress, GFAP Reactivity, and Purkinje Cell Loss in the Cerebellum of Male Rats After 12, 18, and 24 Months of Treatment.","authors":"Daniel Juarez, Berenice Venegas, Dalia Molina-Romero, Ruben Vazquez-Roque, Jose Albino Moreno-Rodriguez, Fabian Galindo-Ramirez, Samuel Treviño, Jorge Guevara, Alfonso Diaz","doi":"10.1002/syn.70040","DOIUrl":"10.1002/syn.70040","url":null,"abstract":"<p><p>The cerebellum contributes to motor, cognitive, and affective functions that progressively decline with aging. The search for effective therapies to delay age-related degeneration has become a focus of the scientific community. Resveratrol, a natural polyphenol, exhibits neuroprotective properties through antioxidant and anti-inflammatory actions in different models of brain injury and aging. Here, we evaluated the effects of resveratrol on fine motor performance, oxidative stress, glial reactivity, and Purkinje cell survival in the cerebellum of male Wistar rats treated for 6, 12, 18, or 24 months. Three-month-old rats were randomly assigned to receive either vehicle (drinking water) or resveratrol (10 mg/kg, orally, daily by gavage between 8:00 and 10:00 a.m.). Fine motor skills were assessed using the balance beam test. Rats treated with resveratrol for 18 or 24 months showed improved motor coordination and fewer slips compared with controls. Histological analysis revealed less cellular disorganization and greater preservation of Purkinje cells after 12, 18, and 24 months of treatment. Nissl staining confirmed that resveratrol attenuated neuronal disintegration and preserved cerebellar architecture. Moreover, resveratrol significantly reduced GFAP immunoreactivity at 12, 18, and 24 months, indicating decreased astrocytic activation and inflammation. In conclusion, chronic resveratrol treatment exerted neuroprotective effects in the cerebellum, improving fine motor performance and reducing glial reactivity. These findings support resveratrol as a potential strategy to mitigate motor decline, inflammation, and cerebellar neurodegeneration associated with aging.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"80 2","pages":"e70040"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114428","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":"Protective Role of miR-3909 Against Propofol-Induced Neurotoxicity Through the Regulation of Polymerase I and Transcript Release Factor.","authors":"Xiangyu Lu, Yuanzhu Li, Haitao Lou, Zhiqiang Feng, Chuancheng Zong","doi":"10.1002/syn.70041","DOIUrl":"10.1002/syn.70041","url":null,"abstract":"<p><p>Propofol (PPF), a commonly employed clinical anesthetic, has elicited growing concern due to its associated neurotoxic effects. However, the functional role and mechanistic insights of microRNA-3909 (miR-3909) in PPF-induced neurotoxicity remain unexplored. This study sought to elucidate the expression of miR-3909 and its underlying molecular mechanisms in the context of PPF-induced neurotoxicity. An in vitro model of  PPF neurotoxicity was established using SH-SY5Y cells (PPF-SH-SY5Y). Initial assessments via cell counting kit-8 (CCK-8) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) demonstrated that treatment with 50 µM PPF significantly reduced cell viability and downregulated miR-3909 expression. Subsequent functional assays revealed that overexpression of miR-3909 effectively alleviated PPF-induced neurotoxicity, as evidenced by enhanced cell viability, suppression of apoptosis, reduced lactate dehydrogenase (LDH) release, and decreased reactive oxygen species (ROS) levels. Mechanistic investigations, including a dual-luciferase reporter assay, validated that miR-3909 directly targets and negatively regulates the expression of polymerase I and transcript release factor (PTRF). Notably, PTRF was significantly upregulated in PPF-SH-SY5Y cells, and overexpression of PTRF substantially counteracted the neuroprotective effects mediated by miR-3909. Collectively, these findings indicate that miR-3909 alleviates propofol-induced neurotoxicity by targeting PTRF, thereby providing a potential therapeutic target for this condition.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"80 2","pages":"e70041"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147322040","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":"Sevoflurane Triggers Glial Cell Damage Through BLACAT1/miR-361-3p Axis Resulting in Cognitive Impairment.","authors":"Jipeng Wen, Feiyu Long, Xiaoying Wang","doi":"10.1002/syn.70043","DOIUrl":"10.1002/syn.70043","url":null,"abstract":"<p><p>To investigate the regulatory mechanism of BLACAT1 expression in sevoflurane (Sev)-induced neuronal cell injury. An in vitro model was created by treating microglial cell lines with 3% Sev. An in vivo model was created by administering 2.2% Sev gas inhalation to mice for three consecutive days. Learning and memory capacity was assessed using the Morris water maze test. Gene expression was detected via RT-qPCR, while cellular functional alterations were observed through CCK-8 assays and flow cytometry. ELISA monitored inflammatory cytokine levels, while assay kits assessed oxidative stress marker expression. Dual luciferase reporter assay and RNA immunoprecipitation validated gene-target relationships. Treatment with Sev increased BLACAT1 levels in microglia and mouse hippocampi, while reducing the expression of miR-361-3p. Transfection with si-BLACAT1 counteracted the inhibitory effects of Sev on cell proliferation while reducing inflammatory and oxidative stress levels. miR-361-3p was a downstream target of BLACAT1, with miR inhibitor counteracting si-BLACAT1's protective effects on damaged neurons. Furthermore, Sev treatment impaired learning and memory functions in the mouse hippocampus, as evidenced by prolonged escape latency and fewer platform crossings during the original platform phase. BLACAT1 participates in Sev-induced glial cell injury via miR-361-3p, leading to hippocampal cognitive dysfunction.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"80 2","pages":"e70043"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345011","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":"Chronic Gallic Acid Treatment Attenuates Hippocampal Neurodegeneration in Aged Rats.","authors":"Sonia Irais Gonzalez-Cano, Daniel Juarez-Serrano, Anabella Handal, José Luis Morán Perales, Rubén A Vázquez-Roque, Fabián Galindo-Ramírez, Samuel Treviño, Jorge Guevara, Alfonso Díaz","doi":"10.1002/syn.70036","DOIUrl":"10.1002/syn.70036","url":null,"abstract":"<p><p>In recent years, global life expectancy has risen significantly, leading to a marked increase in the elderly population. Aging disproportionately affects the brain, resulting in cognitive decline and increased susceptibility to neurodegenerative diseases. This vulnerability is largely due to the high metabolic activity of neural tissue and its sensitivity to reactive oxygen species (ROS). Consequently, oxidative and inflammatory processes are key contributors to cellular damage and age-related cognitive deficits. These oxidative processes may act as primary drivers of neuronal damage during aging. Recent evidence suggests that phenolic compounds may play a crucial role in neuroprotective strategies. Among these, gallic acid (GA) has garnered attention due to its potent antioxidant and anti-inflammatory properties, which enhance neuronal resilience in animal models. However, the effects of GA on hippocampal neurodegeneration during aging remain unclear. In this study, we evaluated the impact of GA on learning, memory, redox balance, neuroinflammation, apoptosis, and synaptic plasticity in the hippocampus (Hp) of aged rats. Male rats aged 18 months received a daily dose of GA (20 mg/kg) for 60 days. GA treatment significantly improved short- and long-term recognition memory. In the Hp, ROS, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and lipid peroxidation were reduced, while superoxide dismutase (SOD) and catalase (CAT) activities increased. GA administration also decreased caspase-3 expression. Collectively, these findings indicate that GA enhances antioxidant and anti-inflammatory defenses, thereby mitigating hippocampal damage and supporting its potential as a promising therapeutic strategy to prevent or reduce neurodegenerative disorders associated with aging.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"80 1","pages":"e70036"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744748","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":"Role and Mechanism of miR-101b-3p via Targeting TXNIP in Sevoflurane-Induced Cognitive Impairment in Mice.","authors":"Haitao Lou, Haibo Yang, Feifei Chen","doi":"10.1002/syn.70038","DOIUrl":"10.1002/syn.70038","url":null,"abstract":"<p><p>Sevoflurane may trigger neuroinflammation, thereby leading to cognitive dysfunction. This study aimed to investigate the mechanism of microRNA-101b-3p (miR-101b-3p) in sevoflurane-induced hippocampal neurodegeneration. In this study, 48 male C57BL/6 mice were procured to establish an animal model of cognitive dysfunction. The expression of miR-101b-3p and thioredoxin-interacting protein (TXNIP) was quantified using real-time quantitative polymerase chain reaction (RT-qPCR), and their targeting relationship was validated through a dual-luciferase reporter assay. The Morris water maze test was employed to assess the cognitive ability of mice. The concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in hippocampal tissues were measured via enzyme-linked immunosorbent assay (ELISA). A detection kit was utilized to evaluate the activity of superoxide dismutase (SOD), malondialdehyde (MDA) content, and reactive oxygen species (ROS) levels. Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2) proteins were determined by Western blotting. Sevoflurane treatment not only reduced the expression of miR-101b-3p but also concurrently increased the expression of TXNIP. Overexpression of miR-101b-3p was capable of suppressing TXNIP expression and alleviating sevoflurane-induced cognitive dysfunction, inflammatory response, and oxidative stress. Conversely, overexpression of TXNIP reversed these protective effects. Moreover, sevoflurane exposure may induce apoptosis, as indicated by elevated Bax and reduced Bcl-2 expression. However, overexpression of miR-101b-3p inhibited apoptosis, and this effect was counteracted by TXNIP supplementation. Overexpression of miR-101b-3p suppressed the expression of TXNIP, thereby attenuating the inflammatory response and oxidative stress and mitigating sevoflurane-induced cognitive dysfunction.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"80 1","pages":"e70038"},"PeriodicalIF":2.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775691","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":"Genome-Wide Translatome Analysis Following Low-Dose Ketamine to Reveal Novel Targets for Antidepressant Treatment.","authors":"Oliver H Miller, Nils Grabole, Isabelle Wells, Ludovic Bellier, Jonathan J Nassi, Benjamin J Hall","doi":"10.1002/syn.70033","DOIUrl":"10.1002/syn.70033","url":null,"abstract":"<p><p>Low-dose ketamine is an efficacious antidepressant for treatment-resistant unipolar and bipolar depressed patients. Major depressive disorder patients receiving a single infusion report elevated mood within 2 h, and ketamine's antidepressant effects have been observed as long as 7 days posttreatment. In light of this remarkable observation, efforts have been undertaken to \"reverse-translate\" ketamine's effects to understand its mechanism of action. Major advances have been achieved in understanding the molecular, cellular, and circuit-level changes that are initiated by low-dose ketamine. Although enhancement of protein synthesis clearly plays a role, the field lacks a comprehensive understanding of the protein synthesis program initiated after ketamine treatment. Here, using ribosome-bound mRNA footprinting and deep sequencing (RiboSeq), we uncovered a genome-wide set of actively translated mRNAs (the translatome) in medial prefrontal cortex after an acute antidepressant-like dose of ketamine. Gene Ontology analysis confirmed that initiation of protein synthesis is a defining feature of antidepressant-dose ketamine in mice, and Gene Set Enrichment Analysis pointed to a role for GPCR signaling, metabolism, vascularization, and structural plasticity in ketamine's effects. One gene, VIPR2, whose protein product VPAC2 acts as a GPCR for the neuropeptide vasoactive intestinal peptide, was characterized in the cortex and identified as a potential novel target for antidepressant action. We demonstrate that VPAC2's functional expression in medial prefrontal cortex is limited to somatostatin-positive neurons and that in vivo dosing of a VPAC2 agonist elicits complex effects on prefrontal cortical pyramidal neurons, bidirectionally modulating their activity and disrupting the structure of coordinated neural activity. Finally, we show that VPAC2 agonism is sufficient to drive an antidepressant response, confirming the validity of our approach to targeted drug development.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 6","pages":"e70033"},"PeriodicalIF":2.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12627282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549951","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":"Isoflurane Promotes Neuroinflammation and Induces Cognitive Impairment Through the miR-3099-5p/AQP4 Axis.","authors":"Xiangshuo Meng, Pengzhou Tang, Shengquan Cheng, Xin Zhang, Peng Zhao, Huiwen Guan, Jiahao Zhang, Xiao Zhang, Junjie Feng, Linyu Sui, Xufang Sun, Xueling Zu","doi":"10.1002/syn.70032","DOIUrl":"10.1002/syn.70032","url":null,"abstract":"<p><strong>Background: </strong>Isoflurane is an inhalational anesthetic widely used in clinical practice. However, its potential neurotoxic mechanisms have not been fully elucidated. Recent studies have found that miR-3099-5p is stably expressed in the brain and is closely associated with neural injury, neurodevelopment, and stem cell differentiation.</p><p><strong>Method: </strong>This study utilized an isoflurane-treated SD rat model to assess the effects of isoflurane on the spatial learning and memory capabilities of the rats through the Morris water maze experiment system. ELISA technology was employed to measure the levels of inflammatory factors, while the thiobarbituric acid reactive substance method and WST-1/NBT colorimetric method were used to determine oxidative stress indicators. Furthermore, qRT-PCR technology was applied to detect gene expression levels, and the regulatory relationships between target genes were further examined through dual-luciferase reporter gene assays.</p><p><strong>Result: </strong>Exposure to isoflurane can lead to cognitive dysfunction in rats, accompanied by an upregulation of miR-3099-5p expression. Additionally, inhibiting miR-3099-5p not only significantly improves these cognitive deficits but also attenuates the isoflurane-induced inflammatory response of microglia and oxidative stress, with the mechanism being through direct targeting and inhibition of AQP4 expression.</p><p><strong>Conclusion: </strong>miR-3099-5p mediates isoflurane-induced neurotoxicity via AQP4 regulation. Its inhibition alleviates cognitive impairment and neuroinflammation, providing a novel therapeutic target for anesthesia-related neural damage and potential neuroprotective drug development.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 6","pages":"e70032"},"PeriodicalIF":2.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186769","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 Mechanism by Which RMRP Regulates Diabetic Peripheral Neuropathy via the miR-3142.","authors":"Mimi Wang, Tenghui Fu, Jinfeng Yang, Wei Yan, Menglie Zhang","doi":"10.1002/syn.70034","DOIUrl":"10.1002/syn.70034","url":null,"abstract":"<p><p>This study aims to investigate the role of long noncoding RNA RMRP in diabetic peripheral neuropathy (DPN) and its potential mechanisms. We used high glucose (HG) treatment on Schwann cells (SCs) and established a DPN rat model to study the role of RMRP in DPN. RT-qPCR was employed to assess the levels of RMRP and miR-3142. The targeting relationship between RMRP and miR-3142 was verified through dual-luciferase reporter assays, RIP assays, and RNA pull-down experiments. CCK-8 assays and flow cytometry were used to evaluate cell proliferation and apoptosis. The von Frey test and thermal stimulus apparatus measured the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in rats. In addition, the motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the rats were assessed. RMRP was abnormally expressed in both HG-treated SCs and DPN rats. Inhibition of RMRP significantly alleviated the reduction in SCs proliferation and the increase in apoptosis induced by HG, while also reducing oxidative stress and neuroinflammation levels. In DPN rats, inhibition of RMRP improved MWT and TWL and enhanced nerve conduction velocity, whereas inhibition of miR-3142 diminished the protective effects of si-RMRP. Inhibiting RMRP can relieve DPN-related oxidative stress and cell inflammation, as well as reduce pain hypersensitivity and the decline in nerve conduction velocity in rats by upregulating miR-3142.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 6","pages":"e70034"},"PeriodicalIF":2.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337558","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":"Inhibition of miR-378a-3p Protects Anesthesia-Induced Hippocampal Neurodegeneration.","authors":"Junxiao Chang, Quan Lin, Yanyan Jiang, Dalong Wang, Lei Che, Meiqing Du, Shuai Wang, Yu Zhang","doi":"10.1002/syn.70027","DOIUrl":"10.1002/syn.70027","url":null,"abstract":"<p><p>Ketamine is widely used in pediatric anesthesia, but it may induce cortical neuronal damage, leading to apoptosis, neurofibrillary degeneration, and even cell death. miRNAs can regulate the neurotoxicity induced by ketamine in hippocampal neurons. This article explores the role of miR-378a-3p in ketamine-induced impairments, providing a reference for preventing hippocampal neurodegenerative lesions induced by anesthesia. The expression of miR-378a-3p and AdipoR1 was detected in hippocampal tissues and HT22 cells. To confirm the targeting interaction between miR-378a-3p and AdipoR1, dual-luciferase reporter assays were performed. Cellular viability and apoptosis were also assessed. Ketamine upregulates the expression of miR-378a-3p and downregulates the expression of AdipoR1 in hippocampal tissues and cells, impairing cognitive function in rats. Following ketamine induction, the levels of TNF-α, IL-1β, IL-6, caspase-3, ROS, and MDA are increased, while the level of SOD is decreased in rat hippocampal tissues and cells. Knocking down miR-378a-3p inhibits oxidative stress injury and the release of inflammatory factors by upregulating the expression of AdipoR1. These findings indicate that inhibition of miR-378a-3p protects hippocampal neurons from ketamine-induced damage by upregulating AdipoR1.This suggests that inhibiting miR-378a-3p protects hippocampal neuronal cells from Ketamine-induced damage by upregulating AdipoR1. The study indicates that miR-378a-3p/AdipoR1 axis is a crucial pathway regulating ketamine-induced cognitive impairments and hippocampal neurodegenerative lesions.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 5","pages":"e70027"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970039","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":"Amygdala-Dependent Signaling Pathways and Regulating Circuits in Fear Memory.","authors":"Meng-Qi Huang, Xi-Lan Liang, Xiao-Tong Lin, Wen-Hui Li, Yi-Han Jiang, Fei Geng","doi":"10.1002/syn.70026","DOIUrl":"10.1002/syn.70026","url":null,"abstract":"<p><p>Fear memory, a profound emotional memory formed in response to threatening events, is vital to the survival and adaptation of individuals. The amygdala, a central hub in the formation, storage, and expression of fear memory, extensively connects with other brain regions, particularly the hippocampus and hypothalamus, allowing it to rapidly integrate sensory information and generate emotional responses. Past research on the regulatory circuits of fear memory has focused on the amygdala, prefrontal cortex, and hippocampus, emphasizing their interactive roles in the formation, consolidation, and extinction of fear memory. However, new circuits and signaling pathways have been identified, leaving many unresolved mysteries about the specific mechanisms of signaling pathways and circuits that depend on the amygdala in fear memories. Therefore, this review focuses on the roles of the different signaling pathways and circuits of the amygdala in fear memories, including their interactions with the hippocampus, cortex, and other brain regions. Further, synaptic plasticity and the regulation of inhibitory interneurons in the amygdala by the ventral prefrontal cortex are discussed. The aims of this review are to advance our understanding of the amygdala's mechanism in fear memory, provide new insights for the prevention and treatment of related disorders such as post-traumatic stress disorder (PTSD), and offer guidance for future research.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 5","pages":"e70026"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785368","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}