Fouad El-Dana, Kenneth Aldape, Zied Abdullaev, Sameer Anil Sheth, Jacob Mandel, Hsiang-Chih Lu
{"title":"Low-grade glial/glioneuronal tumor with YAP1::FAM118B fusion: A novel molecular finding.","authors":"Fouad El-Dana, Kenneth Aldape, Zied Abdullaev, Sameer Anil Sheth, Jacob Mandel, Hsiang-Chih Lu","doi":"10.1093/jnen/nlae103","DOIUrl":"https://doi.org/10.1093/jnen/nlae103","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Regina R Reimann, Dorothee Gramatzki, Andrea Bink, Jürgen Hench, Stephan Frank, Martina Haberecker, Tibor Hortobagyi, Kristof Egervari, Doron Merkler, Kenneth Aldape, Michael Weller
{"title":"Long survival in a patient with fumarate hydratase mutation-associated glioma.","authors":"Regina R Reimann, Dorothee Gramatzki, Andrea Bink, Jürgen Hench, Stephan Frank, Martina Haberecker, Tibor Hortobagyi, Kristof Egervari, Doron Merkler, Kenneth Aldape, Michael Weller","doi":"10.1093/jnen/nlae100","DOIUrl":"https://doi.org/10.1093/jnen/nlae100","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Abstracts of the 100th Annual Meeting June 6-9, 2024 Olympic Valley, California.","authors":"","doi":"10.1093/jnen/nlae102","DOIUrl":"https://doi.org/10.1093/jnen/nlae102","url":null,"abstract":"","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lola E R Lessard, Marie Robert, Tanguy Fenouil, Rémi Mounier, Véréna Landel, Marie Carlesimo, Arnaud Hot, Bénédicte Chazaud, Thomas Laumonier, Nathalie Streichenberger, Laure Gallay
Idiopathic inflammatory myopathies (IIM) are rare, acquired muscle diseases; their diagnosis of is based on clinical, serological, and histological criteria. MHC-I-positive immunostaining, although non-specific, is used as a marker for IIM diagnosis; however, the significance of major histocompatibility complex (MHC)-II immunostaining in IIM remains debated. We investigated patterns of MHC-II immunostaining in myofibers and capillaries in muscle biopsies from 103 patients with dermatomyositis ([DM], n = 31), inclusion body myositis ([IBM], n = 24), anti-synthetase syndrome ([ASyS], n = 10), immune-mediated necrotizing myopathy ([IMNM], n = 18), or overlap myositis ([OM], n = 20). MHC-II immunostaining of myofibers was abnormal in 63/103 of patients (61%) but the patterns differed according to the IIM subgroup. They were diffuse in IBM (96%), negative in IMNM (83%), perifascicular in ASyS (70%), negative (61%) or perifascicular (32%) in DM, and either clustered (40%), perifascicular (30%), or diffuse heterogeneous (15%) in OM. Capillary MHC-II immunostaining also identified quantitative (capillary dropout, n = 47/88, 53%) and qualitative abnormalities, that is, architectural abnormalities, including dilated and leaky capillaries, (n = 79/98, 81%) in all IIM subgroups. Thus, MHC-II myofiber expression patterns allow distinguishing among IIM subgroups. We suggest the addition of MHC-II immunostaining to routine histological panels for IIM diagnosis.
{"title":"Contribution of major histocompatibility complex class II immunostaining in distinguishing idiopathic inflammatory myopathy subgroups: A histopathological cohort study.","authors":"Lola E R Lessard, Marie Robert, Tanguy Fenouil, Rémi Mounier, Véréna Landel, Marie Carlesimo, Arnaud Hot, Bénédicte Chazaud, Thomas Laumonier, Nathalie Streichenberger, Laure Gallay","doi":"10.1093/jnen/nlae098","DOIUrl":"https://doi.org/10.1093/jnen/nlae098","url":null,"abstract":"<p><p>Idiopathic inflammatory myopathies (IIM) are rare, acquired muscle diseases; their diagnosis of is based on clinical, serological, and histological criteria. MHC-I-positive immunostaining, although non-specific, is used as a marker for IIM diagnosis; however, the significance of major histocompatibility complex (MHC)-II immunostaining in IIM remains debated. We investigated patterns of MHC-II immunostaining in myofibers and capillaries in muscle biopsies from 103 patients with dermatomyositis ([DM], n = 31), inclusion body myositis ([IBM], n = 24), anti-synthetase syndrome ([ASyS], n = 10), immune-mediated necrotizing myopathy ([IMNM], n = 18), or overlap myositis ([OM], n = 20). MHC-II immunostaining of myofibers was abnormal in 63/103 of patients (61%) but the patterns differed according to the IIM subgroup. They were diffuse in IBM (96%), negative in IMNM (83%), perifascicular in ASyS (70%), negative (61%) or perifascicular (32%) in DM, and either clustered (40%), perifascicular (30%), or diffuse heterogeneous (15%) in OM. Capillary MHC-II immunostaining also identified quantitative (capillary dropout, n = 47/88, 53%) and qualitative abnormalities, that is, architectural abnormalities, including dilated and leaky capillaries, (n = 79/98, 81%) in all IIM subgroups. Thus, MHC-II myofiber expression patterns allow distinguishing among IIM subgroups. We suggest the addition of MHC-II immunostaining to routine histological panels for IIM diagnosis.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qian-Qian Li,Qi Yu,Zhi-Yi Liu,Qin Zhang,Meng-Yuan Li,Yan Hu
Sevoflurane (Sevo) is widely used for general anesthesia during pregnancy. Emerging evidence indicates that maternal Sevo exposure can trigger developmental neurotoxicity in the offspring. Nonetheless, the underlying mechanisms need further investigation. Pregnant Sprague-Dawley rats on gestational day 18 were exposed to 3.5% Sevo to induce the rat model of neurotoxicity. TAK-242, a TLR4 inhibitor, was administrated to inhibit the signaling transduction. Hippocampal tissues of rat offspring were harvested for immunohistochemical staining, TUNEL staining, Western blotting, ELISA, and measurement of oxidative stress-related markers. Serum samples were collected to evaluate lipid metabolism-associated factors. Morris water maze was implemented to test the cognitive function of offspring rats. Rat hippocampal neurons were isolated to elucidate the effect of TAK-242 on the BDNF/TrkB/CREB signaling in vitro. The results showed that maternal Sevo exposure during the third trimester induced neuroinflammation, lipid metabolism disturbance, and oxidative stress, and impaired the spatial learning and memory of rat offspring. Sevo upregulated TLR4 and impeded BDNF/TrkB/CREB signaling transduction in the hippocampus of rat offspring; TAK-242 administration reversed these effects. In conclusion, Sevo anesthesia during late gestation impairs the learning and memory ability of rat offspring possibly by promoting neuroinflammation and disturbing lipid metabolism via the TLR4/BDNF/TrkB/CREB pathway.
{"title":"Sevoflurane anesthesia during late gestation induces cognitive disorder in rat offspring via the TLR4/BDNF/TrkB/CREB pathway.","authors":"Qian-Qian Li,Qi Yu,Zhi-Yi Liu,Qin Zhang,Meng-Yuan Li,Yan Hu","doi":"10.1093/jnen/nlae096","DOIUrl":"https://doi.org/10.1093/jnen/nlae096","url":null,"abstract":"Sevoflurane (Sevo) is widely used for general anesthesia during pregnancy. Emerging evidence indicates that maternal Sevo exposure can trigger developmental neurotoxicity in the offspring. Nonetheless, the underlying mechanisms need further investigation. Pregnant Sprague-Dawley rats on gestational day 18 were exposed to 3.5% Sevo to induce the rat model of neurotoxicity. TAK-242, a TLR4 inhibitor, was administrated to inhibit the signaling transduction. Hippocampal tissues of rat offspring were harvested for immunohistochemical staining, TUNEL staining, Western blotting, ELISA, and measurement of oxidative stress-related markers. Serum samples were collected to evaluate lipid metabolism-associated factors. Morris water maze was implemented to test the cognitive function of offspring rats. Rat hippocampal neurons were isolated to elucidate the effect of TAK-242 on the BDNF/TrkB/CREB signaling in vitro. The results showed that maternal Sevo exposure during the third trimester induced neuroinflammation, lipid metabolism disturbance, and oxidative stress, and impaired the spatial learning and memory of rat offspring. Sevo upregulated TLR4 and impeded BDNF/TrkB/CREB signaling transduction in the hippocampus of rat offspring; TAK-242 administration reversed these effects. In conclusion, Sevo anesthesia during late gestation impairs the learning and memory ability of rat offspring possibly by promoting neuroinflammation and disturbing lipid metabolism via the TLR4/BDNF/TrkB/CREB pathway.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ischemic stroke is a major cause of global death and permanent disability. Major consequences of ischemic stroke include neuronal mitochondrial dysfunction. We investigated the effects of senescence marker protein 30 (SMP30) on mitochondria-mediated apoptosis and histone deacetylase 4 (HDAC4)/postsynaptic density-95 (PSD-95) signaling in stroke models in vivo and in vitro. Rats with middle cerebral artery occlusion/reperfusion (MCAO/R) were used to simulate cerebral ischemia/reperfusion (I/R) injury. SMP30 was downregulated in the brain tissues of rats after I/R induction. SMP30 overexpression decreased MCAO/R-induced infarct volumes and improved neurologic function and histopathological changes. Increasing SMP30 expression suppressed neuronal apoptosis and reduced mitochondrial dysfunction. SMP30 overexpression in SH-SY5Y and PC12 cells treated with oxygen-glucose deprivation/reoxygenation (OGD/R) decreased HDAC4 and PSD-95 expression; PSD-95 could bind to HDAC4. Furthermore, HDAC4 upregulation abolished the effects of SMP30 overexpression on OGD/R-induced apoptosis and mitochondrial dysfunction in SH-SY5Y cells. Together, these findings indicate that SMP30 alleviates cerebral I/R-induced neuronal injury by inhibiting HDAC4/PSD-95 to preserve mitochondrial function. These interactions might provide new treatment methods for patients with ischemic stroke.
{"title":"SMP30 alleviates cerebral ischemia/reperfusion-induced neuronal injury by inhibiting HDAC4/PSD-95 to preserve mitochondrial function.","authors":"Rundong Chen,Lei Qian,Qian Zhang,Jiajun Qin,Xianzhen Chen,Xiaolong Xu","doi":"10.1093/jnen/nlae095","DOIUrl":"https://doi.org/10.1093/jnen/nlae095","url":null,"abstract":"Ischemic stroke is a major cause of global death and permanent disability. Major consequences of ischemic stroke include neuronal mitochondrial dysfunction. We investigated the effects of senescence marker protein 30 (SMP30) on mitochondria-mediated apoptosis and histone deacetylase 4 (HDAC4)/postsynaptic density-95 (PSD-95) signaling in stroke models in vivo and in vitro. Rats with middle cerebral artery occlusion/reperfusion (MCAO/R) were used to simulate cerebral ischemia/reperfusion (I/R) injury. SMP30 was downregulated in the brain tissues of rats after I/R induction. SMP30 overexpression decreased MCAO/R-induced infarct volumes and improved neurologic function and histopathological changes. Increasing SMP30 expression suppressed neuronal apoptosis and reduced mitochondrial dysfunction. SMP30 overexpression in SH-SY5Y and PC12 cells treated with oxygen-glucose deprivation/reoxygenation (OGD/R) decreased HDAC4 and PSD-95 expression; PSD-95 could bind to HDAC4. Furthermore, HDAC4 upregulation abolished the effects of SMP30 overexpression on OGD/R-induced apoptosis and mitochondrial dysfunction in SH-SY5Y cells. Together, these findings indicate that SMP30 alleviates cerebral I/R-induced neuronal injury by inhibiting HDAC4/PSD-95 to preserve mitochondrial function. These interactions might provide new treatment methods for patients with ischemic stroke.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alzheimer disease (AD) is a prevalent neurodegenerative disorder that affects synapses and leads to progressive cognitive decline. The role of N-methyl-D-aspartic acid (NMDA) receptors in the pathogenesis of AD is well-established as they contribute to excitotoxicity and neurodegeneration in the pathological process of extrasynaptic glutamate concentration. However, the therapeutic potential of the NMDA receptor antagonist memantine in rescuing synaptic damage is limited. Research indicates that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors also play a significant role in AD. Abnormal transcription, expression, and localization of AMPA receptors lead to synaptic dysfunction and damage, contributing to early cognitive impairment in AD patients. Understanding the impact of AMPA receptors on AD pathogenesis and exploring the potential for the development of AMPA receptor-targeting drugs are crucial. This review aims to consolidate recent research findings on AMPA receptors in AD, elucidate the current state of AMPA receptor research and lay the foundation for future basic research and drug development.
阿尔茨海默病(AD)是一种流行的神经退行性疾病,会影响突触并导致认知能力逐渐下降。N-甲基-D-天冬氨酸(NMDA)受体在阿兹海默病发病机制中的作用已得到证实,因为它们在突触外谷氨酸浓缩的病理过程中导致兴奋毒性和神经变性。然而,NMDA 受体拮抗剂美金刚在挽救突触损伤方面的治疗潜力有限。研究表明,α-氨基-3-羟基-5-甲基-4-异恶唑丙酸盐(AMPA)受体在 AD 中也起着重要作用。AMPA 受体的转录、表达和定位异常会导致突触功能障碍和损伤,从而造成 AD 患者的早期认知功能障碍。了解AMPA受体对AD发病机制的影响以及探索开发AMPA受体靶向药物的潜力至关重要。本综述旨在整合近期有关AD中AMPA受体的研究成果,阐明AMPA受体的研究现状,为未来的基础研究和药物开发奠定基础。
{"title":"AMPA receptors in Alzheimer disease: Pathological changes and potential therapeutic targets.","authors":"Luying Ning, Rongjing Shen, Bingqing Xie, Yong Jiang, Xiaoqi Geng, Wei Dong","doi":"10.1093/jnen/nlae093","DOIUrl":"https://doi.org/10.1093/jnen/nlae093","url":null,"abstract":"<p><p>Alzheimer disease (AD) is a prevalent neurodegenerative disorder that affects synapses and leads to progressive cognitive decline. The role of N-methyl-D-aspartic acid (NMDA) receptors in the pathogenesis of AD is well-established as they contribute to excitotoxicity and neurodegeneration in the pathological process of extrasynaptic glutamate concentration. However, the therapeutic potential of the NMDA receptor antagonist memantine in rescuing synaptic damage is limited. Research indicates that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors also play a significant role in AD. Abnormal transcription, expression, and localization of AMPA receptors lead to synaptic dysfunction and damage, contributing to early cognitive impairment in AD patients. Understanding the impact of AMPA receptors on AD pathogenesis and exploring the potential for the development of AMPA receptor-targeting drugs are crucial. This review aims to consolidate recent research findings on AMPA receptors in AD, elucidate the current state of AMPA receptor research and lay the foundation for future basic research and drug development.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Glioblastomas (GBM), the most common primary brain tumor, lack accurate prognostic markers and have a poor prognosis. Our study was designed to identify effective biomarkers for GBM prognosis analysis and development of precise treatments. Differentially expressed genes (DEGs) between GBM patients and controls were analyzed from the Xena database and GEPIA. Based on the screened DEGs, univariate COX and LASSO regression analysis were performed to identify the most relevant genes associated with GBM prognosis. Genes highly expressed in GBM patients were selected to construct receiver operating characteristic analysis and enrichment analysis was constructed on groups of high and low expression of adipocyte enhancer-binding protein 1 (AEBP1). CIBERSORT, ssGSEA and ESTIMATE were used to perform immune infiltration analysis. About 3297 DEGs were identified using data from Xena database; 8 prognostic genes were identified. AEBP1, which plays a role in neuronal differentiation and development, was positively correlated in GBMs with immune infiltration; its high expression in cancer patients is associated with short overall survival and advanced tumor staging. This study suggests that AEBP1 could serve as a prognostic marker for GBMs and that patients with high expression may have a better response to immunotherapy.
{"title":"Clinical significance and potential mechanism of AEBP1 in glioblastoma.","authors":"Chengcheng Wang, Huan Han, Fang Cheng, Hao Wang, Junlong Wang, Chong Lv, Shibin Jiang, Yan Peng, Xiaoling Zhao","doi":"10.1093/jnen/nlae091","DOIUrl":"https://doi.org/10.1093/jnen/nlae091","url":null,"abstract":"<p><p>Glioblastomas (GBM), the most common primary brain tumor, lack accurate prognostic markers and have a poor prognosis. Our study was designed to identify effective biomarkers for GBM prognosis analysis and development of precise treatments. Differentially expressed genes (DEGs) between GBM patients and controls were analyzed from the Xena database and GEPIA. Based on the screened DEGs, univariate COX and LASSO regression analysis were performed to identify the most relevant genes associated with GBM prognosis. Genes highly expressed in GBM patients were selected to construct receiver operating characteristic analysis and enrichment analysis was constructed on groups of high and low expression of adipocyte enhancer-binding protein 1 (AEBP1). CIBERSORT, ssGSEA and ESTIMATE were used to perform immune infiltration analysis. About 3297 DEGs were identified using data from Xena database; 8 prognostic genes were identified. AEBP1, which plays a role in neuronal differentiation and development, was positively correlated in GBMs with immune infiltration; its high expression in cancer patients is associated with short overall survival and advanced tumor staging. This study suggests that AEBP1 could serve as a prognostic marker for GBMs and that patients with high expression may have a better response to immunotherapy.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lijiang He, Jingfang Ye, Xunrong Zhuang, Jinnan Shi, Wenhua Wu
Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) attenuate inflammatory responses in the central nervous system, leading to neuroprotective effects. Inhibition of histone deacetylase 3 (HDAC3) has neuroprotective effects after spinal cord injury (SCI) through the SIRT1 pathway, but the pathophysiological mechanisms of SCI are complex and the interactions between ω-3 PUFAs and organelles remain largely unknown. This study aimed to investigate the effect of ω-3 PUFAs on endoplasmic reticulum (ER) stress-induced neuroinflammation through the HDAC3/peroxisome proliferator-activated receptor-γ coactivator (PGC)-1ɑ pathway after SCI. To this end, a contusion-induced SCI rat model was established to evaluate the effects of ω-3 PUFAs on ER stress-mediated inflammation in SCI. ER stress was rapidly induced in spinal cord lesions after SCI and was significantly reduced after ω-3 PUFA treatment. Consistent with reduced ER stress, HDAC3 expression levels and inflammatory responses were decreased, and PGC-1ɑ expression levels were increased after SCI. We found that ω-3 PUFA treatment attenuated ER stress through HDAC3 inhibition, thereby reducing SCI-induced inflammation. Taken together, these results suggest a role for ω-3 PUFA in protecting against SCI-induced neuroinflammation and promoting neurological functional recovery by regulating the histone deacetylase 3/ peroxisome proliferator-activated receptor-γ coactivator pathway.
欧米伽-3 多不饱和脂肪酸(ω-3 PUFAs)可减轻中枢神经系统的炎症反应,从而起到神经保护作用。抑制组蛋白去乙酰化酶3(HDAC3)可通过SIRT1途径对脊髓损伤(SCI)后的神经产生保护作用,但SCI的病理生理机制十分复杂,ω-3 PUFA与细胞器之间的相互作用在很大程度上仍是未知的。本研究旨在探讨ω-3 PUFAs通过HDAC3/过氧化物酶体增殖体激活受体-γ辅助激活剂(PGC)-1ɑ途径对SCI后内质网(ER)应激诱导的神经炎症的影响。为此,我们建立了挫伤诱导的 SCI 大鼠模型,以评估 ω-3 PUFA 对 SCI 中 ER 应激介导的炎症的影响。SCI 后脊髓病变迅速诱发 ER 应激,ω-3 PUFA 治疗后ER 应激显著降低。与ER应激降低相一致的是,HDAC3表达水平和炎症反应均降低,而PGC-1ɑ表达水平在SCI后升高。我们发现,ω-3 PUFA 治疗通过抑制 HDAC3 减轻了 ER 应激,从而减少了 SCI 诱导的炎症。综上所述,这些结果表明ω-3 PUFA可通过调节组蛋白去乙酰化酶3/过氧化物酶体增殖激活受体-γ辅助激活剂通路,在防止SCI诱导的神经炎症和促进神经功能恢复方面发挥作用。
{"title":"Omega-3 polyunsaturated fatty acids alleviate endoplasmic reticulum stress-induced neuroinflammation by protecting against traumatic spinal cord injury through the histone deacetylase 3/ peroxisome proliferator-activated receptor-γ coactivator pathway.","authors":"Lijiang He, Jingfang Ye, Xunrong Zhuang, Jinnan Shi, Wenhua Wu","doi":"10.1093/jnen/nlae094","DOIUrl":"https://doi.org/10.1093/jnen/nlae094","url":null,"abstract":"<p><p>Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) attenuate inflammatory responses in the central nervous system, leading to neuroprotective effects. Inhibition of histone deacetylase 3 (HDAC3) has neuroprotective effects after spinal cord injury (SCI) through the SIRT1 pathway, but the pathophysiological mechanisms of SCI are complex and the interactions between ω-3 PUFAs and organelles remain largely unknown. This study aimed to investigate the effect of ω-3 PUFAs on endoplasmic reticulum (ER) stress-induced neuroinflammation through the HDAC3/peroxisome proliferator-activated receptor-γ coactivator (PGC)-1ɑ pathway after SCI. To this end, a contusion-induced SCI rat model was established to evaluate the effects of ω-3 PUFAs on ER stress-mediated inflammation in SCI. ER stress was rapidly induced in spinal cord lesions after SCI and was significantly reduced after ω-3 PUFA treatment. Consistent with reduced ER stress, HDAC3 expression levels and inflammatory responses were decreased, and PGC-1ɑ expression levels were increased after SCI. We found that ω-3 PUFA treatment attenuated ER stress through HDAC3 inhibition, thereby reducing SCI-induced inflammation. Taken together, these results suggest a role for ω-3 PUFA in protecting against SCI-induced neuroinflammation and promoting neurological functional recovery by regulating the histone deacetylase 3/ peroxisome proliferator-activated receptor-γ coactivator pathway.</p>","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}