Synapse最新文献

{"title":"miR-138-5p Alleviates Abnormal Pain and Neuroinflammation in Postherpetic Neuralgia by Inhibiting ROCK2.","authors":"Shuang Chen, Qiu Jin, Xia Geng, Xiaona Guo, Tingting Wang, Jingjing Xu, Linkai Jiang, Qing Su","doi":"10.1002/syn.70031","DOIUrl":"10.1002/syn.70031","url":null,"abstract":"<p><p>Postherpetic neuralgia (PHN) is a form of neuropathic pain that has significant detrimental effects. This study seeks to explore the potential association between miR-138-5p and PHN. A PHN model was established by infecting rats with the varicella-zoster virus. Following this, the expression level of miR-138-5p in spinal cord was quantified using RT-qPCR. To further investigate its role, miR-138-5p levels were modulated through the intrathecal administration of a lentivirus. The abnormal pain sensitivity in the rats was assessed utilizing the paw withdrawal threshold (PWT). Additionally, the levels of glial fibrillary acidic protein (GFAP) and pro-inflammatory cytokines (IL-1β and TNF-α) in spinal cord were measured by RT-qPCR or enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was used to verify the binding relationship between miR-138-5p and ROCK2. miR-138-5p is downregulated in the spinal cord tissue of PHN rats. Notably, the overexpression of miR-138-5p significantly enhances the PWT in PHN rats. Furthermore, the elevation of miR-138-5p markedly mitigates the abnormal increase of GFAP and pro-inflammatory factors. Mechanistically, ROCK2 has been identified as a downstream target of miR-138-5p. During the onset of PHN, ROCK2 is persistently upregulated, whereas the overexpression of miR-138-5p effectively inhibits this increase. Interestingly, the concurrent overexpression of miR-138-5p and ROCK2 can counteract the enhancement in PWT engendered solely by the upregulation of miR-138-5p, alongside the reduction in levels of GFAP, IL-1β, and IL-6. miR-138-5p plays a crucial role in modulating the development of PHN. In the context of PHN, miR-138-5p inhibits spinal cord inflammation and hyperalgesia by suppressing ROCK2.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 5","pages":"e70031"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150919","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":"Acetylation of Histones in the Nucleus Accumbens Increases the Expression of Dopamine Transporters to Regulate Executive Function in Sapap3 Knockout Mice.","authors":"Hanrui Shi, Jianqun Fang, Yanrong Wang, Yundong Chen, Yuan Wang, Deshang Dai","doi":"10.1002/syn.70029","DOIUrl":"10.1002/syn.70029","url":null,"abstract":"<p><p>Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric condition characterized by persistent, intrusive thoughts (obsessions) and repetitive ritualistic behaviors (compulsions). Accumulating evidence suggests that individuals with OCD demonstrate marked cognitive impairments, especially in executive function domains, including cognitive flexibility and working memory. Although existing therapeutic approaches (e.g., serotonin reuptake inhibitors and cognitive-behavioral therapy) can partially mitigate behavioral symptoms, their effectiveness in improving cognitive impairments remains limited. Although dopaminergic dysregulation has been implicated in OCD, the involvement of dopamine transporter (DAT) polymorphisms in cognitive flexibility and working memory impairments remains unclear, limiting the development of targeted therapeutic interventions. Although current investigations predominantly focus on dopamine (DA) D1/D2 receptors and serotonin transporters, the contribution of the DAT to OCD pathophysiology remains insufficiently explored. In the present study, we utilized Sapap3 knockout (KO) mice as a preclinical OCD model to examine dopaminergic dysregulation. Using ELISA, we conducted systematic comparisons of both dopaminergic levels and DAT expression between Sapap3 KO and wild-type (WT) mice. Additionally, we implemented targeted epigenetic modulation via histone acetylation in the nucleus accumbens (NAc) of Sapap3 KO mice. Our data demonstrated a significant decrease in DAT expression in the NAc of Sapap3 KO mice compared to WT (p = 0.0019). Strikingly, the administration of the histone deacetylase inhibitor 4-phenylbutyric acid (PBA) normalized DAT expression in KO mice to levels statistically equivalent to WT mice (p = 0.1107), achieving complete functional recovery of DAT deficiency. This restoration of DAT expression (p = 0.1107 PBA vs. WT) was accompanied by a significant reduction in the abnormally elevated baseline DA levels in Sapap3 KO mice (pretreatment: 192.46 ± 6.69 pg/mg; posttreatment: 173.67 ± 4.10 pg/mg, p < 0.01), which consequently improved executive function impairments. Our findings demonstrate that DAT polymorphisms represent a previously unrecognized pathogenic factor in cognitive impairment associated with OCD. Investigations of histone acetylation regulatory mechanisms revealed that changes in histone acetylation levels directly regulate DAT expression. We provide mechanistic evidence showing that epigenetic regulation of DAT expression can effectively reverse these neurological deficits, particularly through modulation of histone acetylation status to significantly improve DAT functional abnormalities, thereby identifying a novel and promising therapeutic target for OCD treatment.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 5","pages":"e70029"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993333","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":"Berberine-Induced Behavioral Effects on Tail Suspension Test, BDNF, and CREB Levels in the Prefrontal Cortex, Hippocampus, and Amygdala: Modulation by Central Serotonergic Transmission.","authors":"Venu Anand Das Vaishnav, Richa Patel, Vaibhav Maturkar, Chhatrapal Patel, Nishant Sudhir Jain","doi":"10.1002/syn.70028","DOIUrl":"10.1002/syn.70028","url":null,"abstract":"<p><p>Berberine has demonstrated an antidepressant-like effect in rodents. Moreover, it increases central 5-hydroxytryptamine (5-HT)/brain-derived neurotrophic factor (BDNF) or cyclic AMP response element binding protein (CREB) levels, but the exact role of these targets in its effect is still ill-explained. Therefore, the present study explored the role of 5-HT in berberine-induced antidepressant-like activity and BDNF or CREB expression in the specific brain regions. Administration of berberine (2, 5, and 20 mg/kg, i.p.) significantly reduced the duration of immobility of mice in the tail suspension test (TST) model without affecting locomotor activity, confirming its antidepressant-like potential. Preinjection with the 5-HT precursor, 5-hydroxytryptophan (5-HTP; 50 and 100 µg/mouse, intracerebroventricular [i.c.v.]), and the selective serotonin reuptake inhibitor (SSRI), fluoxetine (5 and 10 mg/kg, i.p.), enhanced the berberine-induced antidepressant-like effect, whereas it was reversed in mice pretreated with 5-HT_1A receptor agonist, 8-hydroxy-2(-dipropylamino)tetralinhydrobromide (8-OH-DPAT) (0.01 and 0.1 µg/mouse, i.c.v.), or the 5-HT_2A/2C receptor antagonist, mianserin (1, 1.5 µg/mouse, i.c.v.). Furthermore, berberine-induced antidepressant-like effects were significantly reduced in mice with depleted central 5-HT, achieved by preinjection of the serotonin depletor, p-chlorophenylalanine (p-CPA; 300 mg/kg, i.p. × 3 days). Additionally, berberine (20 mg/kg, i.p.) treatment significantly elevated BDNF expression in the whole brain, prefrontal cortex (PFC), and hippocampus and increased CREB expression in the whole brain and hippocampus only. Notably, berberine-induced elevated BDNF expression in the whole brain and hippocampus was further enhanced in mice pretreated with 5-HTP, fluoxetine, or 8-OH-DPAT, whereas mianserin or p-CPA reversed it. However, 5-HTP enhanced and fluoxetine or 8-OH-DPAT did not alter, whereas mianserin or p-CPA reversed the berberine-induced heightened BDNF expression in the PFC. On the other hand, berberine significantly increased CREB expression in the whole brain, which was further potentiated in mice pretreated with 5-HTP, fluoxetine, 8-OH-DPAT, or mianserin, whereas it was reversed by p-CPA. However, berberine-induced heightened CREB expression in the hippocampus was enhanced only in mice pretreated with 5-HTP and attenuated by preinjection of mianserin or p-CPA. These findings suggest that serotonergic transmission modulates the antidepressant-like activity and the BDNF/CREB alterations induced by berberine, likely through a mechanism mediated by 5-HT_1A and 5-HT_2A/2C receptors. This study underscores the role of serotonergic transmission in the effects induced by berberine.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 5","pages":"e70028"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970042","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":"miR-365a-3p Alleviates Isoflurane-Induced Neuroinflammation and Cognitive Impairment by Targeting MyD88 to Inhibit NF-κB Signaling.","authors":"Shujuan Bai, Peng Shi","doi":"10.1002/syn.70025","DOIUrl":"10.1002/syn.70025","url":null,"abstract":"<p><p>Isoflurane (ISO) exposure is associated with neuroinflammation and postoperative cognitive dysfunction (POCD) in aged populations, although the underlying mechanisms remain unclear. This study aimed to determine whether ISO-induced cognitive decline involves miR-365a-3p and its downstream signaling targets. Aged rats were exposed to ISO to establish a POCD model. Cognitive and motor functions were evaluated using Morris water maze tests and neurological scoring. The expression of miR-365a-3p, inflammatory factors, synaptic proteins, and apoptotic markers in the hippocampus was measured by qRT-PCR, ELISA, and Western blotting. In vitro, LPS-treated BV-2 microglia were co-cultured with differentiated SH-SY5Y neurons to assess neuronal apoptosis rate (by flow cytometry) and synaptic integrity. Dual-luciferase reporter assays verified the direct interaction between miR-365a-3p and MyD88. ISO exposure reduced hippocampal miR-365a-3p, resulting in memory/motor deficits, increased pro-inflammatory factors, microglial activation, synaptic protein loss, and neuronal apoptosis. Adding extra miR-365a-3p reversed these problems. LPS treatment reduced miR-365a-3p expression and enhanced pro-inflammatory cytokine production in BV-2 cells, which subsequently induced apoptosis in co-cultured neurons and impaired synaptic integrity. These conditions were reversed by miR-365a-3p overexpression. Mechanistically, miR-365a-3p directly targeted MyD88, inhibiting its expression and downstream NF-κB activation. MyD88 overexpression reversed protective effects of miR-365a-3p on inflammation and synaptic function. ISO causes POCD by reducing miR-365a-3p, which protects the brain by blocking MyD88/NF-κB. Boosting miR-365a-3p may represent a potential strategy to help prevent ISO-related brain harm in elderly patients, warranting further translational investigation.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 5","pages":"e70025"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795543","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":"[¹²⁵I]IPPI for Tau Imaging: Binding Studies in Postmortem Human Alzheimer's Disease Hippocampus-Subiculum and Evaluation of Drug Effects.","authors":"Fariha Karim, Brooke A Delaney, Rommani Mondal, Christopher Liang, Geidy E Serrano, Thomas G Beach, Jogeshwar Mukherjee","doi":"10.1002/syn.70024","DOIUrl":"10.1002/syn.70024","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterized by the accumulation of tau tangles that aggregate into neurofibrillary tangles (NFT). This study aims to assess binding of [¹²⁵I]IPPI, a recently reported imaging probe for pathological, aggregated tau in AD human hippocampus (HP) postmortem brain slices, and measure effects of drugs known to bind to tau, monoamine oxidase A (MAO-A), and dual specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A). Quantitative [¹²⁵I]IPPI binding was compared between AD (n = 29; 13 male and 16 female) and cognitively normal (CN) (n = 32; 16 male and 16 female) subjects. Significantly, there was more [¹²⁵I]IPPI binding in AD gray matter (GM), which positively correlated with the percent of anti-tau immunostaining. GM/white matter (WM) ratios in AD were higher compared to CN subjects. Female AD (avg. GM/WM = 2.42) exhibited greater [¹²⁵I]IPPI binding compared to males (avg. GM/WM = 1.91). Binding of [¹²⁵I]IPPI increased with Braak neurofibrillary stages of the subjects, and the effects of aging were mixed, with females showing a downward trend. A positive correlation between [¹²⁵I]IPPI binding to tau and [¹⁸F]flotaza binding to amyloid beta (Aβ) suggests potential pathophysiological associations between the two AD biomarkers. MK-6240 (aggregated tau-selective) and harmine (MAO-A, DYRK1A, and tau nonselective) inhibited [¹²⁵I]IPPI binding by 88% and 69%, respectively. No effect on [¹²⁵I]IPPI binding was observed by selective DYRK1A (KuFal194) and MAO-A (clorgyline) inhibitors. Affinity of harmine for tau binding sites was quantified by inhibitor concentration (IC₅₀) = 135 ± 29 nM. This study demonstrates promise of radiolabeled IPPI as a viable and selective tau radiotracer to assist in the diagnostic imaging of AD in humans.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 4","pages":"e70024"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12230280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576222","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":"Efficacy of Mitochondrial Transfer in Healing Toxin-Induced Damage to Neuromuscular Junction, an Empirical Study.","authors":"Michael R Deschenes, Max Rackley, Sophie Fernandez, Megan Heidebrecht, Kate Hamilton, Hector G Paez, Christopher R Paez, Stephen E Alway","doi":"10.1002/syn.70022","DOIUrl":"10.1002/syn.70022","url":null,"abstract":"<p><p>Neuromuscular diseases and damage affect many people of all ages and are responsible for an exorbitant medical cost, more than $200 million annually. Accordingly, finding an appropriate model to investigate potential curative interventions is necessary. One currently used involves the application of toxic agents on skeletal muscle followed by mitochondrial transplant therapy. A question regarding this model is whether such toxins impact not only muscle tissue but also the neuromuscular junctions (NMJs) responsible for exciting the muscle tissue. This question was addressed here by forming four experimental groups of C57BL/six mice (10-14 per group) that were 8-12 weeks of age: 1) controls whose muscles had not been injured or treated, 2) muscles taken from mice that were injured and then treated with mitochondrial supplement, 3) muscles that had not been injured but were still treated with mitochondria, and 4) muscles that were injured and received no mitochondrial treatment. Several pre- and postsynaptic features of NMJs were subject to immunofluorescent staining procedures before having morphological features assessed with confocal microscopy. Results revealed that only postsynaptic acetylcholine (ACh) receptors showed any significant (p < 0.05) between-group differences, including decreased area size and perimeter length around ACh receptor clusters in injured NMJs. However, presynaptic nerve terminal branching was not different (p > 0.05) among treatment groups, and structural features were not different between groups with the exception of dispersion of postsynaptic receptors. Overall, these results suggest that skeletal muscles damaged with toxin accurately mimic what occurs during toxin-induced damage and post-injury recovery and can be used as a faithful model of occurrences during damage to NMJs as a result of muscle damage along with recovery from that insult.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 4","pages":"e70022"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192259","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":"miR-330-5p Attenuates Isoflurane-Induced Neuroinflammation and Cognitive Dysfunction by Regulating EPHB3.","authors":"Wei Wei Yang, Nan Wang, Qian Yun Zhang, Yu Fei Guan, Si Li Wang, Rui Chen Ma","doi":"10.1002/syn.70020","DOIUrl":"10.1002/syn.70020","url":null,"abstract":"<p><p>It has been shown that isoflurane induces persistent neuroinflammation, which can cause morphological and functional changes in brain, leading to cognitive impairment. It is known that miRNAs play an important regulatory role in hippocampal neurodevelopment and plasticity. This study was to investigate the effect of miR-330-5p on isoflurane-induced cognitive deficits in rats and hippocampal neuronal cell lines and to study the underlying mechanisms. Cognitive performance in rats exposed to isoflurane was assessed using the Morris water maze (MWM) test. The levels of inflammation and oxidative stress markers were quantified using enzyme-linked immunosorbent assays (ELISA). Additionally, luciferase reporter assays were employed to validate the interaction between miR-330-5p and its target genes. Isoflurane exposure led to increased miR-330-5p expression in the hippocampal tissues of rats. Suppression of miR-330-5p enhanced cognitive performance, as evidenced by longer durations spent in the target quadrant and reduced escape latencies. Furthermore, isoflurane-induced hippocampal neuronal apoptosis, inflammation, and oxidative stress were alleviated by both a miR-330-5p inhibitor and EPHB3 silencing. Notably, EPHB3 was identified as a direct regulatory target of miR-330-5p. MiR-330-5p exerts neuroprotective effects in rats by regulating EPHB3, which is associated with inflammatory responses, oxidative stress and neuronal apoptosis mediated by the miR-330-5p/EPHB3 axis.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 4","pages":"e70020"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162318","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":"Monitoring Cortical Spreading Depolarization: Advancements and Applications in Neurocritical Care: A Scoping Review.","authors":"Dalynah Maldonado-McGrath, Ariel Sacknovitz, Esewi Aifuwa, Sophie Kronen, Ankita Jain, Andre Calixte, Ahmed Elmashad, Fawaz Al-Mufti","doi":"10.1002/syn.70021","DOIUrl":"10.1002/syn.70021","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Cortical spreading depolarization (CSD) describes a slow, sustained depolarization within the cerebral gray matter that renders neurons unable to fire action potentials, resulting in widespread neuronal depression. CSD has been observed in stroke, subarachnoid hemorrhage, epilepsy, traumatic brain injury, and migraines and is a potential indicator of imminent neuronal death. Therefore, the identification, monitoring, and treatment of CSD are crucial in both neurointensive care and neurosurgical settings. Such measures are paramount for optimizing outcomes among patients with neurological injuries. However, this slow-spreading depolarization at high amplitudes presents challenges to identifying and monitoring CSD in clinical settings. We aim to identify various current and potential techniques for monitoring CSD in neurocritical care and neurosurgical settings, alongside exploring available treatment modalities. We also analyze current limitations in the detection of CSD, including the identification of potential biomarkers. A brief comprehensive scoping review of available literature utilizing search engines such as PubMed and Google Scholar was conducted using key search terms such as \"cortical spreading depression\", \"CSD\", \"spreading depolarization\", and \"CSD monitoring\". Eligibility for this review was restricted to full-text, English, peer-reviewed literature articles. There were no restrictions on publication dates. Around 450 articles discussing CSD were reviewed and ultimately 65 articles were included in the analysis. Electrocorticography (ECoG), an invasive modality that involves placing electrodes on the brain tissue directly, remains the primary modality to detect CSD, both in the neurosciences intensive care unit (NSICU) and during neurosurgical procedures. However, there are other potential modalities for detection such as Electroencephalogram (EEG), pressure reactivity index (PRx), magnetoencephalography (MEG), MRI/fMRI, and laser speckle imaging (LSI). These methods have been tested in animal models and/or in clinical practice but each has drawbacks that render these modalities not readily available or nonfunctional as independent detection methods in the NSICU. Nevertheless, a multimodal monitoring approach utilizing a combination of monitoring modalities such as ECoG in conjunction with tools that measure cerebral vascular response such as cerebral perfusion pressure, cerebral blood flow, and PRx could provide timely measurements of CSD. There are potential biomarkers being studied for early detection of CSD which include adenosine, GFAP, lactate, IL-6, or TNF-alpha. Some treatment modalities that have been studied that inhibit or halt CSD include: topiramate, valproate, propranolol, amitriptyline, methysergide, Propofol, and glutamate receptor inhibitors. Although several methods have been studied, invasive ECoG remains the gold standard for CSD detection. There are currently no reliable non-invasive modalities for CSD det","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 4","pages":"e70021"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182991","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":"Upregulation of miR-22-3p Alleviates Hyperalgesia and Neuroinflammation Caused by Migraine.","authors":"Lijun Yang, Feng Li, Linlin Guo, Shengnan Qi, Pengcheng Liu","doi":"10.1002/syn.70017","DOIUrl":"10.1002/syn.70017","url":null,"abstract":"<p><strong>Objective: </strong>Migraines profoundly impact patients' quality of life. This study seeks to investigate the relationship between dysregulated miR-22-3p and the neuroinflammation and central sensitization associated with migraine.</p><p><strong>Methods: </strong>Initially, the level of miR-22-3p in migraine patients were analyzed using RT-qPCR. Subsequently, a migraine model was established by administering nitroglycerin (NTG) to mice. To modulate the levels of miR-22-3p within this model, agomir was utilized. Following this intervention, mechanical and thermal pain sensitivity were evaluated by Von Frey filament and radiant heat. The levels of c-Fos, CGRP, TNF-α, IL-1β, and IL-6 in trigeminal nucleus caudalis (TNC) were detected by RT-qPCR and ELISA. Furthermore, dual luciferase reporting assays were conducted to ascertain whether miR-22-3p could target KLF6. Moreover, the influence of KLF6 on inflammatory cytokines and central sensitization were further studied.</p><p><strong>Results: </strong>miR-22-3p was significantly reduced in migraine patients and NTG mice. In animals, overexpression of miR-22-3p significantly alleviated hyperalgesia and neuroinflammation induced by NTG. Following the overexpression of miR-22-3p, we observed an increase in thermal withdrawal latency, paw mechanical threshold, and periorbital mechanical threshold. Conversely, levels of c-Fos, CGRP, TNF-α, IL-1β, and IL-6 exhibited a significant reduction. We found that miR-22-3p can inhibit KLF6 expression. Additionally, further findings indicated that the suppression of KLF6 resulted in decreased pain sensitivity along with diminished expression of c-Fos, CGRP, TNF-α, IL-1β, and IL-6.</p><p><strong>Conclusion: </strong>In the context of migraine, miR-22-3p may play a pivotal role in mitigating neuroinflammation and alleviating central sensitization through the inhibition of KLF6.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 3","pages":"e70017"},"PeriodicalIF":2.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998376","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":"Increased Expression of Synaptic Vesicle Glycoprotein 2A (SV2A) in the Brain of Chronic Diabetic Rats.","authors":"Burcu Azak Pazarlar, Cansu Bilister Egilmez, Eser Öz Oyar, Jens D Mikkelsen","doi":"10.1002/syn.70018","DOIUrl":"10.1002/syn.70018","url":null,"abstract":"<p><strong>Aim/hypothesis: </strong>Diabetes mellitus has been reported to be a risk factor for cognitive dysfunction, depression, stroke, and seizures. Diabetic pathology is believed to interfere with synaptic plasticity. Synaptic vesicle glycoprotein 2A (SV2A) is a presynaptic vesicular protein and a popular synaptic density imaging marker. We investigated the effect of chronic hyperglycemia on the expression of SV2A in the cerebral cortex and hippocampus of rats and compared it to other presynaptic markers, such as GAP43, Synaptotagmin-1, and SNAP25.</p><p><strong>Methods: </strong>A single dose of streptozotocin (STZ, 45 mg/kg, i.p.) was administered to adult male rats, resulting in sustained hyperglycemia and reduced plasma insulin levels. Controls were injected with saline, and another STZ group was treated with insulin. Fasting blood glucose (FBG) and fasting plasma insulin (FPI) levels were monitored throughout the observation period, and the level of SV2A was determined by radioligand, [³H]UCB-J, binding capacity using in-vitro autoradiography and by ELISA. Similarly, the tissue concentration of other synaptic proteins GAP43, SNAP25, and SYN1 was measured using ELISA. Quantitative RT-qPCR was performed to measure Sv2a, Sv2b, and Sv2c transcripts. Finally, hippocampal and cortical glutamate levels were measured in all tissues.</p><p><strong>Results: </strong>[³H]UCB-J binding, SV2A (pg/mg protein) and Sv2a mRNA levels were significantly higher in hyperglycemic rats. The SV2A concentration detected by ELISA and [³H]UCB-J binding showed, as expected, a positive correlation with each other. The same positive and significant correlation was seen between SV2A, FBG, and glutamate l levels across animals (p ≤ 0.001). Notably, there was no difference and no linearity between FBG and other presynaptic markers such as GAP43, Synaptotagmin-1, and SNAP25.</p><p><strong>Conclusions: </strong>Unlike other synaptic markers (e.g., SNAP25, SYN-1), SV2A levels rise independently of synaptic density, correlating with elevated glutamate and metabolic activity. These findings raise doubt about SV2A's role as a pure synaptic density marker.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"79 3","pages":"e70018"},"PeriodicalIF":2.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049072","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}