Microglial pro-inflammatory activation contributes to neuroinflammatory processes in many neurological disorders. Saturated fatty acids such as palmitic acid (PA) are increasingly recognized as inflammatory cues, yet the molecular mechanisms linking PA to microglial inflammatory responses remain incompletely defined. In this study, using BV-2 microglia as an exploratory in vitro model, we investigated whether C5aR1-sensitive signaling and JMJD3/H3K27me3-related epigenetic changes are involved in PA-associated inflammatory responses. PA exposure increased Iba1 expression, altered CD86/CD206 expression, and enhanced the secretion of IL-1β, IL-6 and TNF-α. Exogenous C5a produced broadly similar inflammatory changes. Under heat-inactivated serum conditions, PA increased cell-associated C5a immunoreactivity and extracellular C5a levels, and these C5a-related readouts were reduced by PMX53. PMX53 also attenuated PA-associated increases in inflammatory markers and in the expression of TLR4, total NF-κB p65, c-Fos, and c-Jun. In parallel, PA and C5a increased JMJD3 expression and JMJD3 enrichment at selected IL-1β and IL-6 promoter regions, accompanied by reduced H3K27me3 enrichment at these loci. Pharmacological KDM6 inhibition with GSK-J4 attenuated PA-associated increases in IL-1β and IL-6 expression. Together, these findings support the involvement of C5aR1-sensitive inflammatory signaling and JMJD3/H3K27me3-related epigenetic regulation in PA-associated microglial inflammatory responses.

Nonsense mutations, responsible for ~11% of gene lesions causing human monogenic diseases, introduce premature termination codons (PTCs) that lead to truncated proteins and nonsense-mediated mRNA decay (NMD). In the central nervous system (CNS), these mutations drive severe, progressive neurological conditions such as spinal muscular atrophy, Rett syndrome, and Duchenne muscular dystrophy. Readthrough therapies-strategies to override PTCs and restore full-length protein expression-have evolved from early aminoglycosides to modern precision tools including suppressor tRNAs, RNA editing, and CRISPR-based platforms. Yet clinical translation remains hampered by inefficient CNS delivery, variable efficacy, and the absence of personalized stratification. In this review, we propose a translational framework-the 4 Ds of Readthrough Therapy-to systematically address these barriers. The framework dissects the pipeline into Detection (precision patient identification and biomarker profiling), Delivery (engineered vectors for CNS targeting), Decoding (context-aware molecular correction), and Durability (long-term safety and efficacy). By integrating advances in machine learning, nanocarriers, base editing, and adaptive trial designs, this roadmap provides a structured strategy to bridge the translational gap. We advocate that a synergistic, modality-tailored approach will transform nonsense suppression from palliative care to durable, precision-based cures for once-untreatable neurological disorders.

OBJECTIVE:SCN1A-related seizures first present as febrile seizures (FS). Definitive features emerge later, making early diagnosis challenging. We evaluated the diagnostic yield and clinical characteristics of pathogenic SCN1A variants in FS, and analyzed the effect of variant characteristics on clinical phenotypes required for early identification and intervention in high-risk patients. METHODS:We analyzed data from a multicenter cohort of 2552 children with FS, no history of afebrile seizures, and no clear alternative diagnosis. Patients underwent gene panel testing for molecular screening. Clinical diagnoses were according to patient history and clinical evaluation. Variant classification followed ACMG guidelines, and the consistency of SCN1A missense variant distribution with the clinical diagnoses and established phenotypic severity was assessed. RESULTS:The diagnostic yield of pathogenic SCN1A variants was 5.5% (141/2552; complex febrile seizure [CFS] vs. simple febrile seizure [SFS] group: 6.8% [95/1389] vs. 4.0% [46/1163], p = 0.001). The proportion of variants associated with Dravet syndrome (DS) did not differ significantly between the groups (χ2 = 1.048; p = 0.306). Missense variants accounted for 76.5% of all pathogenic SCN1A variants, and among previously reported missense variants, those in critical functional domains were frequently associated with severe phenotypes (p = 0.042). However, these domain-specific patterns were not observed when variants were classified into SFS and CFS groups (p = 0.148). Of 106 patients who completed the 1-3-year follow-up, 33 experienced progression to DS. INTERPRETATION:This study demonstrates the limitations of relying solely on clinical classification for FS risk assessment and highlights the clinical value of molecular screening for early risk identification and individualized management.

BACKGROUND:Research has shown gene ATN1 to be associated with the nuclear receptor signaling. Its mutations in an evolutionarily conserved histidine-rich motif may cause CHEDDA, short for congenital hypotonia, epilepsy, developmental delay and digital anomalies, a recently identified neurodevelopmental syndrome that could evolve into developmental and epileptic encephalopathy (DEE). Up to date, there have been reported less than 20 cases, whose clinical features and treatment are worth in-depth exploring.METHODS:The clinical characteristics and genetic data of an infant with CHEDDA and further DEE were analyzed, who carried a de novo ATN1 variant identified by trio whole-exome sequencing. The alike patients with such a neurodevelopmental syndrome and epileptic seizures were reviewed on the literature.RESULTS:The infant harboring a de novo missense mutation in ATN1 (c.3155A>C; p.His1052Pro) held almost all features of CHEDDA and presented with drug-resistant epileptic spasms, differing from one case previously reported with the same gene variant exhibiting milder seizures controlled easily. We further reviewed 11 CHEDDA patients with epileptic seizures in the literature and compared the correlation between abnormal cerebral structure and the incidence of intractable epilepsy among CHEDDA patients. Fortunately, this patient's seizures decreased remarkably after administering ketogenic diet (KD).CONCLUSION:CHEDDA patients have significant phenotypic differences, especially in the epilepsy severity and their drug resistance, even if they carry the same mutation hotspot. Ketogenic diet and other treatments like Topiramate should be recommended for ATN1-related refractory epilepsy based on their regulation on expression of cation-chloride cotransporters and cellular hyperpolarization.

Juvenile parkinsonism is an exceedingly rare condition in which clinical signs of parkinsonism manifest before 21 years of age. Although the genetic underpinnings of this disorder are increasingly recognized, the full range of inherited metabolic contributors remains undefined. We present the first case of levodopa-responsive juvenile parkinsonism associated with dihydropyrimidinase deficiency caused by a novel DPYS variant. A 13-year-old patient presented with rapid progression of dysphagia, dysarthria, and loss of ambulation over 18 months. Whole-exome sequencing revealed compound heterozygous variants in the DPYS gene (NM_001385: c.1393C>T, p.R465X, and c.905G>A, p.R302Q). In silico analysis predicted both variants to be pathogenic. Further urinary metabolome analysis demonstrated markedly elevated dihydrouracil and dihydrothymine levels, confirming impaired pyrimidine metabolism. Levodopa treatment effectively relieved the patient's motor symptoms. This report identifies DPYS as a novel genetic cause of juvenile parkinsonism and underscores the potential efficacy of levodopa therapy in managing motor dysfunction in DYPS-related parkinsonism.

BackgroundWest syndrome (WS) is a devastating epileptic encephalopathy with onset in infancy and early childhood. It is characterized by clustered epileptic spasms, developmental arrest, and interictal hypsarrhythmia on electroencephalogram (EEG). Hypsarrhythmia is considered the hallmark of WS, but its visual assessment is challenging due to its wide variability and lack of a quantifiable definition. This study aims to analyze the EEG patterns in WS and identify computational diagnostic biomarkers of the disease.MethodLinear and non-linear features derived from EEG recordings of 31 WS patients and 20 age-matched controls were compared. Subsequently, the correlation of the identified features with structural and genetic abnormalities was investigated.ResultsWS patients showed significantly elevated alpha-band activity (0.2516 vs. 0.1914, p < 0.001) and decreased delta-band activity (0.5117 vs. 0.5479, p < 0.001), particularly in the occipital region, as well as globally strengthened theta-band activity (0.2145 vs. 0.1655, p < 0.001) in power spectrum analysis. Moreover, wavelet-bicoherence analysis revealed significantly attenuated cross-frequency coupling in WS patients. Additionally, bi-channel coherence analysis indicated minor connectivity alterations in WS patients. Among the four non-linear characteristics of the EEG data (i.e., approximate entropy, sample entropy, permutation entropy, and wavelet entropy), permutation entropy showed the most prominent global reduction in the EEG of WS patients compared to controls (1.4411 vs. 1.5544, p < 0.001). Multivariate regression results suggested that genetic etiologies could influence the EEG profiles of WS, whereas structural factors could not.SignificanceA combined global strengthening of theta activity and global reduction of permutation entropy can serve as computational EEG biomarkers for WS. Implementing these biomarkers in clinical practice may expedite diagnosis and treatment in WS, thereby improving long-term outcomes.

(1) Background: X-linked creatine transporter deficiency (CTD) (OMIM 300036) is a rare group of inherited metabolic disorders characterized by global developmental delay/intellectual disability (GDD/ID), seizures, autistic behavior, and movement disorders. Pathogenic variants in the SLC6A8 gene, located at Xq28, are causative of the disease, leading to impaired creatine transport into the brain. Supplementation with creatine and its precursors, glycine and arginine, has been attempted, yet the treatment efficacy remains controversial. (2) Methods: Here we report a de novo SLC6A8 variant in a boy aged 3 years 9 months presenting with GDD, autistic behavior, and epilepsy. Elevated urinary creatine/creatinine ratio and diminished creatine peak on brain MR spectroscopy suggested the diagnosis of CTD. Genetic sequencing revealed a de novo hemizygous frameshift variant (NM_005629: c.1136_1137del, p. Glu379ValfsTer85). Creatine supplementation therapy was initiated after definitive diagnosis. Electroencephalography and MR spectroscopy were monitored during follow-up in concurrence with neuropsychological evaluations. The clinical phenotype and treatment response of CTD were summarized by systematic view of the literature. (3) Results: In silico analysis showed this variant to be deleterious, probably interfering with substrate binding and conformational changes during creatine transport. Creatine supplementation therapy led to seizure cessation and modest cognitive improvement after half-year's treatment. (4) Conclusions: This case highlights the importance of MR spectroscopy and metabolic screening in males with GDD/ID, allowing for early diagnosis and therapeutic intervention. Mechanistic understanding and case-per-se analysis are required to enable precision treatment for the patients.

Background: N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels that mediate excitatory synaptic trans-mission and brain development in the central nervous system. Mutations in GRIN2D encoding the NMDAR subunit GluN2D are associated with a wide spectrum of neurodevelopmental disorders. Methods: We report a novel de novo GRIN2D variant (NM_000836.2: c.2024C > T, p.Ala675Val) in an infant with severe devel-opmental and epileptic encephalopathy. Clinical characteristics and treatment outcomes of patients with GRIN2D-related develop-mental and epileptic encephalopathy were summarized by reviewing the literature. Results: In silico analysis suggested this p.Ala675Val variant residing in the highly conserved M3 helix of GluN2D would inter-fere with channel gating. Therapeutic options including multiple anticonvulsants, oral corticosteroid therapy, and ketogenic diet failed to achieve seizure control. Eventually, adjunctive therapy with perampanel led to marked electroclinical improvement. Conclusions: Perampanel can be beneficial adjuvant therapy for patients with GRIN2D-related intractable epilepsy. Mechanistic understanding and case-per-se analysis are required to enable more individualized treatment for the patients.(c) 2022 Published by Elsevier B.V. on behalf of The Japanese Society of Child Neurology. All rights reserved.

目的 研究抽动障碍儿童的心理行为问题及相关因素,为合理干预治疗提供依据.方法 采用病例对照研究方法,选择2020年6月至2021年6月华中科技大学同济医学院附属同济医院儿科神经门诊就诊的69名抽动障碍(TD)儿童作为病例组,并按性别与年龄匹配同期69名非TD的正常儿童作为对照组,通过填写一般情况调查表、儿童焦虑性情绪筛查量表41项(SCARED-41)、长处和困难问卷(SDQ-25)及儿童抑郁量表10项(CDI-10)等,分析TD儿童的心理行为问题及相关因素.结果 TD组与对照儿童组SCARED-41总分、SDQ-25总分及SDQ-25困难部分、CDI-10总分分别为(22.1±12.5,13.3±12.3)(21.1±6.0,15.9±3.4)(15.6±6.3,9.3±3.6)(3.7±2.9,2.6±2.9)分,差异有统计学意义(t/Z值分别为3.8,13.9,6.9,-2.6,P值均＜0.05).对TD组儿童的多重线性回归分析显示,母亲学历大学本科对SDQ-25情绪症状、大学专科对SDQ-25亲社会行为(B值分别为-2.20,2.14),父母管教态度宽松对SCARED-41广泛性焦虑、担心对SDQ-25多动(B值分别为-7.44,3.00),电子设备使用时长对SCARED-41躯体化/惊恐、学校恐怖和SDQ-25品行问题(B值分别为0.49,0.30,0.20)及运动强度小强度对CDI-10(B=-0.15)等量表得分影响有统计学意义(P值均＜0.05).结论 TD儿童容易出现焦虑/抑郁情绪及行为问题,并与母亲学历、父母管教态度、电子设备使用时长及运动强度等因素相关.

患儿,男,生后18 d,因"反复抽搐16 d"于2020年9月就诊于华中科技大学同济医学院附属同济医院新生儿科门诊.患儿系第1胎第1产,因"脐带绕颈3周"剖宫产娩出,出生体质量3.2 kg,围产期无窒息缺氧史.母亲孕期无特殊病史.家族中无类似病史.患儿生后第3天无明显诱因出现抽搐,仅表现为四肢抖动,持续数秒后缓解,2～3 h发作1次(均为吃奶时发现).

Phosphoglycerate dehydrogenase (PHGDH) deficiency is a rare autosomal recessive genetic disease of serine biosynthesis. Its typical features are congenital microcephaly, epileptic seizures, and psychomotor developmental delay. Here, we reported the first Chinese familial cases with genetically confirmed PHGDH deficiency and reviewed several previous reports. Two siblings in this family presented with microcephaly, psychomotor retardation, and epilepsy in early juvenile. Brain magnetic resonance imaging (MRI) showed only a slight change of enlarged ventricle. Biochemical investigations revealed low serum serine and glycine concentrations. The whole-exome sequencing (WES) results identified a missense variant in the PHGDH gene (NM_006623.4: exon11: c.1211T>A, p. Val404Asp). Although two patients in this Chinese family carried the same pathogenic mutation in the PHGDH, their symptoms and responses to treatment were not exactly the same. We found a novel variant in the PHGDH gene and expanded the genotypic and phenotypic spectrum of serine biosynthesis disorders.

Background: The human dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) gene encodes a large subunit of the cytoplasmic dynein complex. DYNC1H1 mutations are associated with various neurological diseases involving both the peripheral and central nervous systems. Methods: The clinical characteristics and genetic data of an infant carrying the de novo DYNC1H1 variant identified by trio exome sequencing were analyzed. Patients with epilepsy with DYNC1H1 mutations were summarized by reviewing the literature. Results: We first identified an infant presenting with epileptic spasms harboring a de novo missense mutation in DYNC1H1 (c.874C>T; p. Arg292Trp), once reported in an adult case, and further summarized another 54 patients with seizures or epilepsy caused by DYNC1H1 pathogenic variants in the literature. Refractory epilepsy, intellectual disability, and cortical developmental malformations are crucial characteristics of patients with developmental and epileptic encephalopathy (DEE) caused by DYNC1H1 variants. Notably, epileptic spasms in this case were resistant to multiple anti-seizure medications, corticosteroids, ketogenic diet, and vagus nerve stimulation treatment. The child also showed cortical gyrus malformation and global developmental delay. Conclusion: DYNC1H1 variants can cause infantile developmental and epileptic encephalopathy, in which Arg292Trp is a mutation hotspot of the DYNC1H1 gene. Epileptic seizures in this type of DYNC1H1-related DEE are mostly resistant to multiple antiepileptic strategies and need to explore optimized treatments.

目的 探讨遗传性痉挛性截瘫(HSP)SPG31型的临床特征及REEP1基因突变的致病机制.方法 回顾性分析2018年9月华中科技大学同济医学院附属同济医院儿科收治的一家系HSPSPG31型的临床资料和基因检测结果并进行文献复习.结果 该HSP家系3代共6例成员携带REEP1基因杂合突变c.425del(p.Gly142Valfs*81),该变异属未报道的新发强致病变异,患者临床表现轻重不等,主要表现双下肢无力、走路不稳及痉挛步态,先证者呈缓慢进行性加重.结论 HSP具有显著临床和遗传异质性,REEP1基因新的位点突变可能是引起该家系发病的原因,但确切结论尚需进一步验证.

目的 探讨先天性糖基化障碍(Congenital disorders of glycosylation,CDG)致病基因ALG11(Asparagine-linked glycosylation 11)复合杂合变异致大田原综合征的临床特点、突变致病性分析和治疗手段.方法 回顾分析1例以癫痫发作为首发症状、高通量测序证实CDG致病基因ALG11复合杂合变异致大田原综合征的临床资料、家系基因检测、致病性分析、治疗及随访并作文献复习.结果 患儿,男,5个月23 d,主因"间断抽搐2月余"就诊,癫痫发作早期为部分性发作,后转为痉挛发作、脑电图背景呈爆发-抑制图形,临床诊断大田原综合征;同时患儿反复感染并存在视听障碍、喂养困难、小头畸形、全面性发育迟缓、四肢肌张力高等;采用高通量测序法发现患儿携带ALG11基因(OMIM#613666)c.1403G>A及c.1307G>T复合杂合突变,分别来自其父母并导致p.R468H及p.G436V氨基酸改变,关联疾病为糖基化障碍CDG-1p型;患儿早期给予苯巴比妥/溴化钠合剂及左乙拉西坦口服,癫痫控制效果不佳,联合生酮饮食治疗后癫痫发作逐渐改善,精神运动发育亦有进步.结论 婴儿早发癫痫性脑病合并神经系统多发异常、重复感染时需考虑到CDG可能,生酮饮食辅助疗法可在一定程度上改善癫痫发作.

Objective: GLUT1 deficiency syndrome (GLUT1-DS) is a rare, treatable neurometabolic disorder. However, its diagnosis may be challenging due to the various and evolving phenotypes. Here we report the first Chinese familial cases with genetically confirmed GLUT1-DS and analyze the characteristics of Chinese children with GLUT1-DS from clinical, laboratory, and genetic aspects. Methods: We reported a Chinese family with three members affected with GLUT1-DS and searched for relevant articles up to September 2020 from PubMed, WOS, CNKI, and WanFang databases. A total of 30 Chinese patients diagnosed with GLUT1-DS (three newly identified patients in one family and 27 previously reported ones) were included and analyzed in this study. Results: The median age of onset of the 30 patients (male: 18, female: 12) was 8.5 months (range, 33 days to 10 years). Epileptic seizures were found in 25 patients, most with generalized tonic–clonic and focal ones. Movement disorders were found in 20 patients—frequently with ataxia and dystonia, developmental delay in 25 patients, and microcephaly only in six patients. The cerebrospinal fluid (CSF) analysis showed decreased CSF glucose (median: 1.63 mmol/L, range: 1.1–2.6 mmol/L) and glucose ratio of CSF to blood (median: 0.340; range: 0.215–0.484). The genetic testing performed in 28 patients revealed 27 cases with pathogenic variations of the SLC2A1 gene, including 10 missense, nine frameshift, three nonsense, three large fragment deletions, and two splice-site mutations. Most patients had a good response to the treatment of ketogenic diet or regular diet with increased frequency. Although three patients in this Chinese family carried the same pathogenic mutation c.73C > T (p.Q25X) in the SLC2A1 gene, their symptoms and responses to treatment were not exactly the same. Conclusion: The clinical manifestations of GLUT1-DS are heterogeneous, even among family members sharing the same mutation. For children with unexplained epileptic seizures, developmental delay, and complex movement disorders, detection of low CSF glucose or SLC2A1 gene mutations is helpful for the diagnosis of GLUT1-DS. Early initiation of ketogenic diet treatment significantly improves the symptoms and prognosis of GLUT1-DS.

The human WW domain containing oxidoreductase (WWOX) gene has been identified as a tumor suppressor gene. However, recent reports have demonstrated its dominant role in autosomal recessive disorders of the central nervous system, especially in early onset epileptic encephalopathy. Here, we report a Chinese case with novel compound heterozygous mutation of WWOX gene (c.229_230+2del mutation originated from her mother and c.1065dup (p.Ala356Serfs*173) variation from her father), and compare them to previously reported 59 WWOX-related epileptic encephalopathy (WOREE). Early onset and frequent epileptic seizures in the postnatal period, hypsarrhythmia patterns in EEG background and retarded development are the most important characteristics of WOREE in infants. Although the seizures in our case can be controlled by phenobarbital and topiramate, the prognosis of WOREE is poor.

CD 4 + T cell subset imbalance plays an important role in the development of diabetic complications. Neutrophils have recently been known as the regulator of CD 4 + T cell differentiation. However, whether neutrophils affect CD 4 + T cell population in diabetes is still elusive. In this study, we investigated the effect of neutrophils stimulated with advanced glycated end products (AGEs), the marker of diabetes, on CD 4 + T cell differentiation and its underlying mechanism. Our data showed that the cultural medium of healthy adult neutrophils treated with AGEs increased expressions of both Th 1 (IFN-γ) and Th 17 (IL-17) phenotypes and the transcription factors of Th 1 (Tbet) and Th 17 (RORγt) in naive CD 4 + T cells and CD 4 + CD 25 + FoxP 3 + (Treg) T cells in vitro . Next, we found that AGEs induced the generations of myeloperoxidase (MPO) and neutrophil elastase (NE) in neutrophils; inhibition of MPO or NE attenuated the effect of AGE-stimulated neutrophils on CD 4 + T cell bias. Furthermore, receptor for AGEs (RAGE) inhibitor interrupted AGE-induced MPO and NE expressions, but MPO and NE inhibitions did not change AGE-increased RAGE gene expression. These results suggested that AGEs drive the effect of neutrophils on CD 4 + T cell differentiation into pro-inflammatory program through inducing MPO and NE productions in neutrophils, which is mediated by AGE–RAGE interaction.

The activation of hepatic stellate cells (HSCs) is a major event during hepatic fibrogenesis. Restoration of intracellular lipid droplet (LD) formation turns the activated HSC back to a quiescent state. Our previous studies have shown that curcumin suppresses HSC activation through increasing peroxisome proliferator-activated receptor, gamma (PPARγ) and 5′ adenosine monophosphate-activated protein kinase (AMPK) activities. This study aims at evaluating the effect of curcumin on lipid accumulation in HSCs and hepatocytes, and further elucidating the underlying mechanisms. Now we showed that curcumin increased LD formation in activated HSCs and stimulated the expression of sterol regulatory element-binding protein and fatty acid synthase, and reduced the expression of adipose triglyceride lipase. Exogenous perilin5 expression in primary HSCs promoted LD formation. Perilipin 5 siRNA eliminated curcumin-induced LD formation in HSCs. These results suggest that curcumin recovers LD formation and lipid accumulation in activated HSCs by increasing perilipin 5 gene expression. Furthermore, inhibition of AMPK or PPARγ activity blocked curcumin’s effect on Plin5 gene expression and LD formation. Our results provide a novel evidence in vitro for curcumin as a safe, effective candidate to treat liver fibrosis.

目的 观察棕榈酸(PA)及C5aR拮抗剂(PMX53)干预后小胶质细胞的炎症改变,探讨C5a受体(C5aR)及C5L2在PA诱导的小胶质细胞炎症中的作用.方法 取新生1日龄小鼠,分离脑组织,原代培养小胶质细胞并进行分离纯化及鉴定.纯化小胶质细胞随机分成3组:正常对照组、PA处理组、PA+PMX53处理组.分别应用Western blot检测PA及PA+PMX53干预后小胶质细胞C5aR、C5L2、p38M APK蛋白表达;RT-PCR检测C5L2 mRNA表达及ELISA法检测IL-6表达变化.结果 通过免疫组化鉴定,成功培养小胶质细胞.PA干预后,C5aR蛋白表达较对照组明显上升(P＜0.001),而加入PMX53后,C5aR蛋白表达较PA组显著下降(P＜0.001);PA干预后,C5L2蛋白及mRNA表达较对照组增加(P＜0.001),而加入PMX53后,C5L2蛋白表达与PA组差异无统计学意义(P=0.978),而C5L2 mRNA表达较PA组明显上升(P＜0.001);PA组较对照组p38MAPK蛋白的表达增加(P=0.002),PA+PMX53组p38MAPK蛋白表达较PA组降低(P=0.004);PA干预后,IL-6浓度较对照组显著升高(P＜0.001),而PMX53干预后,PA+PMX53组较PA组IL-6浓度显著下降(P＜0.001).结论 PA可能通过C5a-C5aR激活MAPK信号途径中的p38MAPK通路,从而诱发小胶质细胞炎症反应,而C5L2在此过程中可能发挥抗炎作用.

Objective To observe the effect of complement 5a receptor(C5aR)antagonist(PMX53)and palmitic acid(PA)on the inflammatory reaction of microglia,and to investigate the roles and mechanisms of com-plement C5a-C5aR in PA induced microglia inflammation.Methods Microglia from one day old mice was collect-ed,purified and identified by primary culture and immunohistochemical staining,and then was randomly divided into three groups including PA group,PA+PMX53 group and control group.The expressions of tumor necrosis factor-α(TNF-α),Iba-1 and ERK1/2 were determined by ELISA,Western blot and QT-PCR.Results In PA group, the levels of Iba-1 and TNF-α were higher significantly than the control group(P<0.001).Similarly,the levels of ERK1/2 mRNA(P = 0.005 6)and p-ERK1/2 protein(P < 0.001)in the PA group were higher significantly than that in control group in spite of no difference in ERK1/2 protein in all groups. However,the levels of Iba-1,p-ERK1/2 protein,ERK1/2 mRNA and TNF-α in the PA+PMX53 group were significantly lower than that in the PA group(P<0.001),although there was no difference in ERK1/2 protein in all groups.Conclusions C5a receptor antagonist suppresses inflammatory reaction of microglia induced byPA,suggesting that C5a-C5aR-ERK may par-ticipate in the inflammation of microglia induced byPA. Therefore,C5a receptor antagonist may protect the brain tissues from inflammation-induced damage.