Neurotoxicity Research最新文献_第10页

Dexmedetomidine Promoted HSPB8 Expression via Inhibiting the lncRNA SNHG14/UPF1 Axis to Inhibit Apoptosis of Nerve Cells in AD : The Role of Dexmedetomidine in AD. 右美托咪定通过抑制lncRNA SNHG14/UPF1轴促进HSPB8表达以抑制AD中神经细胞的凋亡：右美托咪定在AD中的作用。

IF 2.9 3区医学

Neurotoxicity Research Pub Date : 2023-10-01 Epub Date: 2023-09-01 DOI: 10.1007/s12640-023-00653-4

QingYun Tan, LiLi Liu, Shuo Wang, QingDong Wang, Yu Sun

{"title":"Dexmedetomidine Promoted HSPB8 Expression via Inhibiting the lncRNA SNHG14/UPF1 Axis to Inhibit Apoptosis of Nerve Cells in AD : The Role of Dexmedetomidine in AD.","authors":"QingYun Tan, LiLi Liu, Shuo Wang, QingDong Wang, Yu Sun","doi":"10.1007/s12640-023-00653-4","DOIUrl":"10.1007/s12640-023-00653-4","url":null,"abstract":"Dexmedetomidine (Dex) is reported to play a neuroprotective role in Alzheimer's disease (AD). However, the specific mechanism remains unclear. Figure out the underlying molecular mechanism of Dex regulating nerve cell apoptosis in the AD model. The AD model in vitro was established after SH-SY5Y cells were treated with Aβ1 - 42 at (10 μM) for 24 h. The interaction among UPF1, lncRNA SNHG14, and HSPB8 was verified by RIP assay. Cell viability, apoptosis, the level of genes, and proteins were detected by CCK-8 assay, flow cytometry, Western blot, and qRT-PCR, respectively. Dex downregulated lncRNA SNHG14 level and inhibited apoptosis of nerve cells. LncRNA SNHG14 overexpression reversed the inhibitory effect of Dex on nerve cell apoptosis in the AD model. LncRNA SNHG14 attenuated HSPB8 mRNA stability by recruiting UPF1. HSPB8 overexpression inhibited apoptosis of nerve cells in the AD model. Moreover, HSPB8 knockdown reversed the inhibitory effect of Dex on nerve cell apoptosis in the AD model. Our study demonstrated that Dex promoted HSPB8 expression via inhibiting the lncRNA SNHG14/UPF1 axis to inhibit nerve cell apoptosis in AD.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"41 5","pages":"471-480"},"PeriodicalIF":2.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10229946","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}

引用次数: 0

NRF2 Antagonizes HIV-1 Tat and Methamphetamine-Induced BV2 Cell Ferroptosis by Regulating SLC7A11. NRF2通过调节SLC7A11拮抗HIV-1Tat和甲基苯丙胺诱导的BV2细胞脱铁性贫血。

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-10-01 Epub Date: 2023-04-15 DOI: 10.1007/s12640-023-00645-4

Shucheng Lin, Hao Cheng, Genmeng Yang, Chan Wang, Chi-Kwan Leung, Shuwei Zhang, Yi Tan, Huijie Zhang, Haowei Wang, Lin Miao, Yi Li, Yizhen Huang, Juan Li, Ruilin Zhang, Xiaofeng Zeng

{"title":"NRF2 Antagonizes HIV-1 Tat and Methamphetamine-Induced BV2 Cell Ferroptosis by Regulating SLC7A11.","authors":"Shucheng Lin, Hao Cheng, Genmeng Yang, Chan Wang, Chi-Kwan Leung, Shuwei Zhang, Yi Tan, Huijie Zhang, Haowei Wang, Lin Miao, Yi Li, Yizhen Huang, Juan Li, Ruilin Zhang, Xiaofeng Zeng","doi":"10.1007/s12640-023-00645-4","DOIUrl":"10.1007/s12640-023-00645-4","url":null,"abstract":"Methamphetamine (METH) and HIV-1 lead to oxidative stress and their combined effect increases the risk of HIV-associated neurocognitive disorder (HAND), which may be related to the synergistic ferroptotic impairment in microglia. Ferroptosis is a redox imbalance cell damage associated with iron overload that is linked to the pathogenic processes of METH and HIV-1. NRF2 is an antioxidant transcription factor that plays a protective role in METH and HIV-1-induced neurotoxicity, but its mechanism has not been fully elucidated. To explore the role of ferroptosis in METH abuse and HIV-1 infection and the potential role of NRF2 in this process, we conducted METH and HIV-1 Tat exposure models using the BV2 microglia cells. We found that METH and HIV-1 Tat reduced the expression of ferroptotic protein GPX4 and the cell viability and enhanced the expression of P53 and the level of ferrous iron, while the above indices were significantly improved with pretreatment of ferrostatin-1. In addition, NRF2 knockdown accelerated METH and HIV-1 Tat-induced BV2 cell ferroptosis accompanied by decreased expression of SLC7A11. On the contrary, NRF2 stimulation significantly increased the expression of SLC7A11 and attenuated ferroptosis in cells. In summary, our study indicates that METH and HIV-1 Tat synergistically cause BV2 cell ferroptosis, while NRF2 antagonizes BV2 cell ferroptotic damage induced by METH and HIV-1 Tat through regulation of SLC7A11. Overall, this study provides potential therapeutic strategies for the treatment of neurotoxicity caused by METH and HIV-1 Tat, providing a theoretical basis and new targets for the treatment of HIV-infected drug abusers.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"41 5","pages":"398-407"},"PeriodicalIF":3.7,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10224533","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}

引用次数: 2

Human Placental Mesenchymal Stem Cell-derived Exosomes in Combination with Hyperbaric Oxygen Synergistically Promote Recovery after Spinal Cord Injury in Rats. 人胎盘间充质干细胞来源的外泌体与高压氧联合使用可协同促进大鼠脊髓损伤后的恢复。

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-10-01 Epub Date: 2023-05-08 DOI: 10.1007/s12640-023-00649-0

Hosna Cheshmi, Hossein Mohammadi, Mitra Akbari, Davood Nasiry, Rafat Rezapour-Nasrabad, Mahdi Bagheri, Beheshteh Abouhamzeh, Mahnaz Poorhassan, Mehri Mirhoseini, Hossein Mokhtari, Esmaeil Akbari, Amir Raoofi

{"title":"Human Placental Mesenchymal Stem Cell-derived Exosomes in Combination with Hyperbaric Oxygen Synergistically Promote Recovery after Spinal Cord Injury in Rats.","authors":"Hosna Cheshmi, Hossein Mohammadi, Mitra Akbari, Davood Nasiry, Rafat Rezapour-Nasrabad, Mahdi Bagheri, Beheshteh Abouhamzeh, Mahnaz Poorhassan, Mehri Mirhoseini, Hossein Mokhtari, Esmaeil Akbari, Amir Raoofi","doi":"10.1007/s12640-023-00649-0","DOIUrl":"10.1007/s12640-023-00649-0","url":null,"abstract":"Spinal cord injury (SCI) is a critical medical condition during which sensorimotor function is lost. Current treatments are still unable to effectively improve these conditions, so it is important to pay attention to other effective approaches. Currently, we investigated the combined effects of human placenta mesenchymal stem cells (hPMSCs)-derived exosomes along with hyperbaric oxygen (HBO) in the recovery of SCI in rats. Ninety male mature Sprague-Dawley (SD) rats were allocated into five equal groups, including; sham group, SCI group, Exo group (underwent SCI and received hPMSCs-derived exosomes), HBO group (underwent SCI and received HBO), and Exo+HBO group (underwent SCI and received hPMSCs-derived exosomes plus HBO). Tissue samples at the lesion site were obtained for the evaluation of stereological, immunohistochemical, biochemical, molecular, and behavioral characteristics. Findings showed a significant increase in stereological parameters, biochemical factors (GSH, SOD, and CAT), IL-10 gene expression and behavioral functions (BBB and EMG Latency) in treatment groups, especially Exo+HBO group, compared to SCI group. In addition, MDA levels, the density of apoptotic cells and gliosis, as well as expression of inflammatory genes (TNF-α and IL-1β) were considerably reduced in treatment groups, especially Exo+HBO group, compared to SCI group. We conclude that co-administration of hPMSCs-derived exosomes and HBO has synergistic neuroprotective effects in animals undergoing SCI.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"41 5","pages":"431-445"},"PeriodicalIF":3.7,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10575137","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}

引用次数: 7

p-Nrf2/HO-1 Pathway Involved in Methamphetamine-induced Executive Dysfunction through Endoplasmic Reticulum Stress and Apoptosis in the Dorsal Striatum. p-Nrf2/HO-1通路通过内质网应激和后纹状体细胞凋亡参与甲基苯丙胺诱导的执行功能障碍。

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-10-01 Epub Date: 2023-05-18 DOI: 10.1007/s12640-023-00650-7

Tao Wei, Jun-Da Li, Yu-Jing Wang, Wei Zhao, Fan Duan, Yan Wang, Ling-Ling Xia, Zhao-Bin Jiang, Xun Song, Yu-Qiong Zhu, Wen-Yi Shao, Ze Wang, Kang-Sheng Bi, Hui Li, Xiao-Chu Zhang, Dong-Liang Jiao

{"title":"p-Nrf2/HO-1 Pathway Involved in Methamphetamine-induced Executive Dysfunction through Endoplasmic Reticulum Stress and Apoptosis in the Dorsal Striatum.","authors":"Tao Wei, Jun-Da Li, Yu-Jing Wang, Wei Zhao, Fan Duan, Yan Wang, Ling-Ling Xia, Zhao-Bin Jiang, Xun Song, Yu-Qiong Zhu, Wen-Yi Shao, Ze Wang, Kang-Sheng Bi, Hui Li, Xiao-Chu Zhang, Dong-Liang Jiao","doi":"10.1007/s12640-023-00650-7","DOIUrl":"10.1007/s12640-023-00650-7","url":null,"abstract":"Methamphetamine (METH) abuse is known to cause executive dysfunction. However, the molecular mechanism underlying METH induced executive dysfunction remains unclear. Go/NoGo experiment was performed in mice to evaluate METH-induced executive dysfunction. Immunoblot analysis of Nuclear factor-E2-related factor 2 (Nrf2), phosphorylated Nrf2 (p-Nrf2), heme-oxygenase-1 (HO-1), Glucose Regulated Protein 78(GRP78), C/EBP homologous protein (CHOP), Bcl-2, Bax and Caspase3 was performed to evaluate the levels of oxidative stress, endoplasmic reticulum (ER) stress and apoptosis in the dorsal striatum (Dstr). Malondialdehyde (MDA) levels and glutathione peroxidase (GSH-Px) activity was conducted to evaluate the level of oxidative stress. TUNEL staining was conducted to detect apoptotic neurons. The animal Go/NoGo testing confirmed that METH abuse impaired the inhibitory control ability of executive function. Meanwhile, METH down-regulated the expression of p-Nrf2, HO-1 and GSH-Px and activated ER stress and apoptosis in the Dstr. Microinjection of Tert-butylhydroxyquinone (TBHQ), an Nrf2 agonist, into the Dstr increased the expression of p-Nrf2, HO-1, and GSH-Px, ameliorated ER stress, apoptosis and executive dysfunction caused by METH. Our results indicated that the p-Nrf2/HO-1 pathway was potentially involved in mediating methamphetamine-induced executive dysfunction by inducing endoplasmic reticulum stress and apoptosis in the dorsal striatum.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"41 5","pages":"446-458"},"PeriodicalIF":3.7,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10281711","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}

引用次数: 0

Exercise Improves Orofacial Pain and Modifies Neuropeptide Expression in a Rat Model of Parkinson's Disease. 在帕金森病大鼠模型中，运动改善口面疼痛并改变神经肽的表达。

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-10-01 Epub Date: 2023-06-02 DOI: 10.1007/s12640-023-00651-6

Karina Henrique Binda, Marucia Chacur, Daniel Oliveira Martins

{"title":"Exercise Improves Orofacial Pain and Modifies Neuropeptide Expression in a Rat Model of Parkinson's Disease.","authors":"Karina Henrique Binda, Marucia Chacur, Daniel Oliveira Martins","doi":"10.1007/s12640-023-00651-6","DOIUrl":"10.1007/s12640-023-00651-6","url":null,"abstract":"Pain is a common non-motor symptom of Parkinson's disease (PD), which often occurs in the early disease stages. Despite the high prevalence, it remains inadequately treated. In a hemi-parkinsonian rat model, we aimed to investigate the neurochemical factors involved in orofacial pain development, with a specific focus on pain-related peptides and cannabinoid receptors. We also evaluated whether treadmill exercise could improve orofacial pain and modulate these mechanisms. Rats were unilaterally injected in the striatum with either 6-hydroxydopamine (6-OHDA) or saline. Fifteen days after stereotactic surgery, the animals were submitted to treadmill exercise (EX), or remained sedentary (SED). Pain assessment was performed before the surgical procedure and prior to each training session. Pain-related peptides, substance P (SP), calcitonin gene-related peptide (CGRP), and transient receptor potential vanilloid type 1 (TRPV1) activation and cannabinoid receptor type 1 (CB1) and type 2 (CB2) were evaluated in the trigeminal nucleus. In order to confirm the possible involvement of cannabinoid receptors, we also injected antagonists of CB1 and CB2 receptors. We confirmed the presence of orofacial pain after unilateral 6-OHDA-injection, which improved after aerobic exercise training. We also observed increased pain-related expression of SP, CGRP and TRPV1 and decreased CB1 and CB2 in the trigeminal ganglion and caudal spinal trigeminal nucleus in animals with PD, which was reversed after aerobic exercise training. In addition, we confirm the involvement of cannabinoid receptors since both antagonists decreased the nociceptive threshold of PD animals. These data suggest that aerobic exercise effectively improved the orofacial pain associated with the PD model, and may be mediated by pain-related neuropeptides and cannabinoid receptors in the trigeminal system.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"41 5","pages":"459-470"},"PeriodicalIF":3.7,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10228985","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}

引用次数: 0

Correction to: The Effects of Long-term, Low-dose β-N-methylamino-L-alanine (BMAA) Exposures in Adult SOD^G93R Transgenic Zebrafish. 更正：长期、低剂量β-N-甲基氨基-L-丙氨酸（BMAA）暴露对成年SODG93R转基因斑马鱼的影响。

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-10-01 DOI: 10.1007/s12640-023-00664-1

Ryan D Weeks, Sandra A Banack, Shaunacee Howell, Preethi Thunga, James S Metcalf, Adrian J Green, Paul A Cox, Antonio Planchart

引用次数: 0

The Effects of Long-term, Low-dose β-N-methylamino-L-alanine (BMAA) Exposures in Adult SOD^G93R Transgenic Zebrafish. 长期、低剂量β-N-甲基氨基-L-丙氨酸（BMAA）暴露对成年SODG93R转基因斑马鱼的影响。

IF 2.9 3区医学

Neurotoxicity Research Pub Date : 2023-10-01 Epub Date: 2023-08-08 DOI: 10.1007/s12640-023-00658-z

Ryan D Weeks, Sandra A Banack, Shaunacee Howell, Preethi Thunga, James S Metcalf, Adrian J Green, Paul A Cox, Antonio Planchart

{"title":"The Effects of Long-term, Low-dose β-N-methylamino-L-alanine (BMAA) Exposures in Adult SODG93R Transgenic Zebrafish.","authors":"Ryan D Weeks, Sandra A Banack, Shaunacee Howell, Preethi Thunga, James S Metcalf, Adrian J Green, Paul A Cox, Antonio Planchart","doi":"10.1007/s12640-023-00658-z","DOIUrl":"10.1007/s12640-023-00658-z","url":null,"abstract":"β-N-Methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria, which has been implicated in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). It is postulated that chronic exposure to BMAA can lead to formation of protein aggregates, oxidative stress, and/or excitotoxicity, which are mechanisms involved in the etiology of ALS. While specific genetic mutations are identified in some instances of ALS, it is likely that a combination of genetic and environmental factors, such as exposure to the neurotoxin BMAA, contributes to disease. We used a transgenic zebrafish with an ALS-associated mutation, compared with wild-type fish to explore the potential neurotoxic effects of BMAA through chronic long-term exposures. While our results revealed low concentrations of BMAA in the brains of exposed fish, we found no evidence of decreased swim performance or behavioral differences that might be reflective of neurodegenerative disease. Further research is needed to determine if chronic BMAA exposure in adult zebrafish is a suitable model to study neurodegenerative disease initiation and/or progression.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"41 5","pages":"481-495"},"PeriodicalIF":2.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10231702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CNTN1 in the Nucleus Accumbens is Involved in Methamphetamine-Induced Conditioned Place Preference in Mice. 小鼠凹凸核中的 CNTN1 参与了甲基苯丙胺诱导的条件性位置偏好。

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-08-01 Epub Date: 2023-04-04 DOI: 10.1007/s12640-023-00640-9

Linxuan Zhang, Zehao Zeng, Xiaoyu Lu, Mengqing Li, Jiayu Yao, Guangjing Zou, Zhaorong Chen, Qian Li, Changqi Li, Fang Li

{"title":"CNTN1 in the Nucleus Accumbens is Involved in Methamphetamine-Induced Conditioned Place Preference in Mice.","authors":"Linxuan Zhang, Zehao Zeng, Xiaoyu Lu, Mengqing Li, Jiayu Yao, Guangjing Zou, Zhaorong Chen, Qian Li, Changqi Li, Fang Li","doi":"10.1007/s12640-023-00640-9","DOIUrl":"10.1007/s12640-023-00640-9","url":null,"abstract":"Methamphetamine (Meth), a commonly used central nervous system stimulant, is highly addictive. Currently, there is no effective treatment for Meth dependence and abuse, although cell adhesion molecules (CAMs) have been shown to play an important role in the formation and remodeling of synapses in the nervous system while also being involved in addictive behavior. Contactin 1 (CNTN1) is a CAM that is widely expressed in the brain; nevertheless, its role in Meth addiction remains unclear. Therefore, in the present study, we established mouse models of single and repeated Meth exposure and subsequently determined that CNTN1 expression in the nucleus accumbens (NAc) was upregulated in mice following single or repeated Meth exposure, whereas CNTN1 expression in the hippocampus was not significantly altered. Intraperitoneal injection of the dopamine receptor 2 antagonist haloperidol reversed Meth-induced hyperlocomotion and upregulation of CNTN1 expression in the NAc. Additionally, repeated Meth exposure also induced conditioned place preference (CPP) in mice and upregulated the expression levels of CNTN1, NR2A, NR2B, and PSD95 in the NAc. Using an AAV-shRNA-based approach to specifically silence CNTN1 expression in the NAc via brain stereotaxis reversed Meth-induced CPP and decreased the expression levels of NR2A, NR2B, and PSD95 in the NAc. These findings suggest that CNTN1 expression in the NAc plays an important role in Meth-induced addiction, and the underlying mechanism may be related to the expression of synapse-associated proteins in the NAc. The results of this study improved our understanding of the role of cell adhesion molecules in Meth addiction.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"41 4","pages":"324-337"},"PeriodicalIF":3.7,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9896282","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}

引用次数: 0

Connexin 43 Promotes Neurogenesis via Regulating Aquaporin-4 after Cerebral Ischemia. 脑缺血后，Connexin 43 通过调节 Aquaporin-4 促进神经发生

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-08-01 Epub Date: 2023-04-19 DOI: 10.1007/s12640-023-00646-3

Heling Chu, Jing Dong, Yuping Tang, Chuyi Huang, Qihao Guo

{"title":"Connexin 43 Promotes Neurogenesis via Regulating Aquaporin-4 after Cerebral Ischemia.","authors":"Heling Chu, Jing Dong, Yuping Tang, Chuyi Huang, Qihao Guo","doi":"10.1007/s12640-023-00646-3","DOIUrl":"10.1007/s12640-023-00646-3","url":null,"abstract":"We aimed to test the effects of connexin43 (Cx43) on ischemic neurogenesis and examined whether it was dependent on aquaporin-4 (AQP4). We detected the expression of Cx43 and AQP4 in the ipsilateral subventricular zone (SVZ) and peri-infarct cortex after middle cerebral artery occlusion (MCAO). Also, we examined neurogenesis in the above regions via co-labeling of 5-bromo-2-deoxyuridine (BrdU)/neuronal nuclear antigen (NeuN) and BrdU/doublecortin (DCX). The effects of Cx43 and AQP4 were investigated by using two transgenic animals: heterozygous Cx43 (Cx43±) mice and AQP4 knockout (AQP4-/-) mice, and connexin mimetic peptide (CMP), a selective Cx43 blocker. We demonstrated AQP4 and Cx43 were co-expressed in the astrocytes after MCAO and the expression was highly increased in ipsilateral SVZ and peri-infarct cortex. Cx43± mice had larger infarction volumes and worse neurological function. Both BrdU/NeuN and BrdU/DCX co-labeled cells in the two regions were reduced in Cx43± and AQP4-/- mice compared to wild-type (WT) mice, suggesting Cx43 and AQP4 participated in neurogenesis of neural stem cells. Moreover, CMP decreased AQP4 expression and inhibited neurogenesis in WT mice, while the latter failed to be observed in AQP4-/- mice. Besides, higher levels of IL-1β and TNF-α were detected in the SVZ and peri-infarct cortex of AQP4-/- and Cx43± mice than those in WT mice. In conclusion, our data suggest that Cx43 elicits neuroprotective effects after cerebral ischemia through promoting neurogenesis in the SVZ to regenerate the injured neurons, which is AQP4 dependent and associated with down-regulation of inflammatory cytokines IL-1β and TNF-α.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"41 4","pages":"349-361"},"PeriodicalIF":3.7,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9858583","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}

引用次数: 0

Microglial Priming in Bilirubin-Induced Neurotoxicity. 胆红素诱导的神经毒性中的小胶质细胞诱导作用

IF 3.7 3区医学

Neurotoxicity Research Pub Date : 2023-08-01 Epub Date: 2023-04-14 DOI: 10.1007/s12640-023-00643-6

Hongmei Huang, Siyu Li, Yan Zhang, Chunmei He, Ziyu Hua

{"title":"Microglial Priming in Bilirubin-Induced Neurotoxicity.","authors":"Hongmei Huang, Siyu Li, Yan Zhang, Chunmei He, Ziyu Hua","doi":"10.1007/s12640-023-00643-6","DOIUrl":"10.1007/s12640-023-00643-6","url":null,"abstract":"Neuroinflammation is a major contributor to bilirubin-induced neurotoxicity, which results in severe neurological deficits. Microglia are the primary immune cells in the brain, with M1 microglia promoting inflammatory injury and M2 microglia inhibiting neuroinflammation. Controlling microglial inflammation could be a promising therapeutic strategy for reducing bilirubin-induced neurotoxicity. Primary microglial cultures were prepared from 1-3-day-old rats. In the early stages of bilirubin treatment, pro-/anti-inflammatory (M1/M2) microglia mixed polarization was observed. In the late stages, bilirubin persistence induced dominant proinflammatory microglia, forming an inflammatory microenvironment and inducing iNOS expression as well as the release of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. Simultaneously, nuclear factor-kappa B (NF-κB) was activated and translocated into the nucleus, upregulating inflammatory target genes. As well known, neuroinflammation can have an effect on N-methyl-D-aspartate receptor (NMDAR) expression or function, which is linked to cognition. Treatment with bilirubin-treated microglia-conditioned medium did affect the expression of IL-1β, NMDA receptor subunit 2A (NR2A), and NMDA receptor subunit 2B (NR2B) in neurons. However, VX-765 effectively reduces the levels of proinflammatory cytokines TNF-α, IL-6, and IL-1β, as well as the expressions of CD86, and increases the expressions of anti-inflammatory related Arg-1. A timely reduction in proinflammatory microglia could protect against bilirubin-induced neurotoxicity.","PeriodicalId":19193,"journal":{"name":"Neurotoxicity Research","volume":"41 4","pages":"338-348"},"PeriodicalIF":3.7,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9842056","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}

引用次数: 0