Synapse最新文献 - Book学术

ERK1/2 Regulates Epileptic Seizures by Modulating the DRP1‐Mediated Mitochondrial Dynamic ERK1/2 通过调节 DRP1 介导的线粒体动态来调控癫痫发作

IF 2.3 4区医学

Synapse Pub Date : 2024-09-17 DOI: 10.1002/syn.22309

Ting Chen, Juan Yang, Yongsu Zheng, Xuejiao Zhou, Hao Huang, Haiqing Zhang, Zucai Xu

{"title":"ERK1/2 Regulates Epileptic Seizures by Modulating the DRP1‐Mediated Mitochondrial Dynamic","authors":"Ting Chen, Juan Yang, Yongsu Zheng, Xuejiao Zhou, Hao Huang, Haiqing Zhang, Zucai Xu","doi":"10.1002/syn.22309","DOIUrl":"https://doi.org/10.1002/syn.22309","url":null,"abstract":"After seizures, the hyperactivation of extracellular signal‐regulated kinases (ERK1/2) causes mitochondrial dysfunction. Through the guidance of dynamin‐related protein 1 (DRP1), ERK1/2 plays a role in the pathogenesis of several illnesses. Herein, we speculate that ERK1/2 affects mitochondrial division and participates in the pathogenesis of epilepsy by regulating the activity of DRP1. LiCl‐Pilocarpine was injected intraperitoneally to establish a rat model of status epilepticus (SE) for this study. Before SE induction, PD98059 and Mdivi‐1 were injected intraperitoneally. The number of seizures and the latency period before the onset of the first seizure were then monitored. The analysis of Western blot was also used to measure the phosphorylated and total ERK1/2 and DRP1 protein expression levels in the rat hippocampus. In addition, immunohistochemistry revealed the distribution of ERK1/2 and DRP1 in neurons of hippocampal CA1 and CA3. Both PD98059 and Mdivi‐1 reduced the susceptibility of rats to epileptic seizures, according to behavioral findings. By inhibiting ERK1/2 phosphorylation, the Western blot revealed that PD98059 indirectly reduced the phosphorylation of DRP1 at Ser616 (p‐DRP1‐Ser616). Eventually, the ERK1/2 and DRP1 were distributed in the cytoplasm of neurons by immunohistochemistry. Inhibition of ERK1/2 signaling pathways downregulates p‐DRP1‐Ser616 expression, which could inhibit DRP1‐mediated excessive mitochondrial fission and then regulate the pathogenesis of epilepsy.","PeriodicalId":22131,"journal":{"name":"Synapse","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255018","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}

引用次数: 0

High Impact AMPAkines Induce a Gq-Protein Coupled Endoplasmic Calcium Release in Cortical Neurons: A Possible Mechanism for Explaining the Toxicity of High Impact AMPAkines. 高强度 AMPAkines 可诱导皮质神经元中 Gq 蛋白偶联的内质钙释放：解释高强度 AMPAkines 毒性的可能机制。

IF 1.6 4区医学

Synapse Pub Date : 2024-09-01 DOI: 10.1002/syn.22310

Daniel P Radin, Sheng Zhong, Rok Cerne, Jeffrey M Witkin, Arnold Lippa

{"title":"High Impact AMPAkines Induce a Gq-Protein Coupled Endoplasmic Calcium Release in Cortical Neurons: A Possible Mechanism for Explaining the Toxicity of High Impact AMPAkines.","authors":"Daniel P Radin, Sheng Zhong, Rok Cerne, Jeffrey M Witkin, Arnold Lippa","doi":"10.1002/syn.22310","DOIUrl":"10.1002/syn.22310","url":null,"abstract":"α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) positive allosteric modulators (AMPAkines) have a multitude of promising therapeutic properties. The pharmaceutical development of high impact AMPAkines has, however, been limited by the appearance of calcium-dependent neuronal toxicity and convulsions in vivo. Such toxicity is not observed at exceptionally high concentrations of low impact AMPAkines. Because most AMPAR are somewhat impermeable to calcium, the current study sought to examine the extent to which different mechanisms contribute to the rise in intracellular calcium in the presence of high impact ampakines. In the presence of AMPA alone, cytosolic calcium elevation is shown to be sodium-dependent. In the presence of high impact AMPAkines such as cyclothiazide (CTZ) or CX614, however, AMPAR potentiation also activates an additional mechanism that induces calcium release from endoplasmic reticular (ER) stores. The pathway that connects AMPAR to the ER system involves a Gq-protein, phospholipase Cβ-mediated inositol triphosphate (InsP3) formation, and ultimately stimulation of InsP3-receptors located on the ER. The same linkage was not observed using high concentrations of the low impact AMPAkines, CX516 (Ampalex), and CX717. We also demonstrate that CX614 produces neuronal hyper-excitability at therapeutic doses, whereas the newer generation low impact AMPAkine CX1739 is safe at exceedingly high doses. Although earlier studies have demonstrated a functional linkage between AMPAR and G-proteins, this report demonstrates that in the presence of high impact AMPAkines, AMPAR also couple to a Gq-protein, which triggers a secondary calcium release from the ER and provides insight into the disparate actions of high and low impact AMPAkines.","PeriodicalId":22131,"journal":{"name":"Synapse","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142295903","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}

引用次数: 0

microRNA-125b-5p alleviated CCI-induced neuropathic pain and modulated neuroinflammation via targeting SOX11. microRNA-125b-5p通过靶向SOX11缓解CCI诱导的神经病理性疼痛并调节神经炎症。

IF 1.6 4区医学

Synapse Pub Date : 2024-09-01 DOI: 10.1002/syn.22306

Liping Wang, Bei Wang, Xia Geng, Xiaona Guo, Tingting Wang, Jingjing Xu, Linkai Jiang, Haining Zhen

{"title":"microRNA-125b-5p alleviated CCI-induced neuropathic pain and modulated neuroinflammation via targeting SOX11.","authors":"Liping Wang, Bei Wang, Xia Geng, Xiaona Guo, Tingting Wang, Jingjing Xu, Linkai Jiang, Haining Zhen","doi":"10.1002/syn.22306","DOIUrl":"10.1002/syn.22306","url":null,"abstract":"Background: Increasing evidence demonstrated the involvement of microRNAs (miRNAs) in the onset and development of neuropathic pain (NP). Exploring the molecular mechanism underlying NP and identifying key molecules could provide potential targets for the therapy of NP. The function and mechanism of miR-125b-5p in regulating NP have been studied, aiming to find a potential therapeutic target for NP.Methods: NP rat models were established by the chronic constriction injury (CCI) method. The paw withdrawal threshold and paw withdrawal latency were assessed to evaluate the establishment and recovery of rats. Highly aggressive proliferating immortalized (HAPI) micoglia cell, a rat microglia cell line, was treated with lipopolysaccharide (LPS). The M1/M2 polarization and inflammation were evaluated by enzyme-linked immunosorbent assay and western blotting.Results: Decreasing miR-125b-5p and increasing SOX11 were observed in CCI rats and LPS-induced HAPI cells. Overexpressing miR-125b-5p alleviated mechanical allodynia and thermal hyperalgesia and suppressed inflammation in CCI rats. LPS induced M1 polarization and inflammation of HAPI cells, which was attenuated by miR-125b-5p overexpression. miR-125-5p negatively regulated the expression of SOX11 in CCI rats and LPS-induced HAPI cells. Overexpressing SOX11 reversed the protective effects of miR-125b-5p on mechanical pain in CCI rats and the polarization and inflammation in HAPI cells, which was considered the mechanism underlying miR-125b-5p.Conclusion: miR-125b-5p showed a protective effect on NP by regulating inflammation and polarization of microglia via negatively modulating SOX11.","PeriodicalId":22131,"journal":{"name":"Synapse","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971846","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}

引用次数: 0

Inhibitory modulation of action potentials in crayfish motor axons by fluoxetine. 氟西汀对小龙虾运动轴突动作电位的抑制性调节。

IF 1.6 4区医学

Synapse Pub Date : 2024-07-01 DOI: 10.1002/syn.22304

Selene Wang, Si Seng Lam, Anisah Aguilar, Stephanie Anakwe, Katherine Barahona, Hani Haider, Olivia Hunyadi, Kaahini Jain, Derek Kolodziejski, Anindita Lal, Man Li, Frank MacKenzie, John Miller, Oliviero Nardin, Emily Nguyen, Jaii Pappu, Melissa Rodriguez, Jen-Wei Lin

{"title":"Inhibitory modulation of action potentials in crayfish motor axons by fluoxetine.","authors":"Selene Wang, Si Seng Lam, Anisah Aguilar, Stephanie Anakwe, Katherine Barahona, Hani Haider, Olivia Hunyadi, Kaahini Jain, Derek Kolodziejski, Anindita Lal, Man Li, Frank MacKenzie, John Miller, Oliviero Nardin, Emily Nguyen, Jaii Pappu, Melissa Rodriguez, Jen-Wei Lin","doi":"10.1002/syn.22304","DOIUrl":"10.1002/syn.22304","url":null,"abstract":"The goal of this report is to explore how K2P channels modulate axonal excitability by using the crayfish ventral superficial flexor preparation. This preparation allows for simultaneous recording of motor nerve extracellular action potentials (eAP) and intracellular excitatory junctional potential (EJP) from a muscle fiber. Previous pharmacological studies have demonstrated the presence of K2P-like channels in crayfish. Fluoxetine (50 µM) was used to block K2P channels in this study. The blocker caused a gradual decline, and eventually complete block, of motor axon action potentials. At an intermediate stage of the block, when the peak-to-peak amplitude of eAP decreased to ∼60%-80% of the control value, the amplitude of the initial positive component of eAP declined at a faster rate than that of the negative peak representing sodium influx. Furthermore, the second positive peak following this sodium influx, which corresponds to the after-hyperpolarizing phase of intracellularly recorded action potentials (iAP), became larger during the intermediate stage of eAP block. Finally, EJP recorded simultaneously with eAP showed no change in amplitude, but did show a significant increase in synaptic delay. These changes in eAP shape and EJP delay are interpreted as the consequence of depolarized resting membrane potential after K2P channel block. In addition to providing insights to possible functions of K2P channels in unmyelinated axons, results presented here also serve as an example of how changes in eAP shape contain information that can be used to infer alterations in intracellular events. This type of eAP-iAP cross-inference is valuable for gaining mechanistic insights here and may also be applicable to other model systems.","PeriodicalId":22131,"journal":{"name":"Synapse","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421035","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}

引用次数: 0

Correction to "Inhibitory modulation of action potentials in crayfish motor axons by fluoxetine". 对 "氟西汀对小龙虾运动轴突动作电位的抑制性调节 "的更正。

IF 1.6 4区医学

Synapse Pub Date : 2024-07-01 DOI: 10.1002/syn.22305

引用次数: 0

Exploring miR-21 as a key regulator in two distinct approaches of bone marrow stromal cells differentiation into Schwann-like cells. 探索 miR-21 作为骨髓基质细胞分化成施万样细胞的两种不同方法中的关键调节因子。

IF 1.6 4区医学

Synapse Pub Date : 2024-05-01 DOI: 10.1002/syn.22293

Yu-Mei Liu, He-Ying Wang, Cai-Hong Wei, Jun-Ping Li, Ying Wang, Wen-Zhi Ma, Hua Jia

{"title":"Exploring miR-21 as a key regulator in two distinct approaches of bone marrow stromal cells differentiation into Schwann-like cells.","authors":"Yu-Mei Liu, He-Ying Wang, Cai-Hong Wei, Jun-Ping Li, Ying Wang, Wen-Zhi Ma, Hua Jia","doi":"10.1002/syn.22293","DOIUrl":"10.1002/syn.22293","url":null,"abstract":"The differentiation of bone marrow stromal cells (BMSCs) into Schwann-like cells (SCLCs) has the potential to promote the structural and functional restoration of injured axons. However, the optimal induction protocol and its underlying mechanisms remain unclear. This study aimed to compare the effectiveness of different induction protocols in promoting the differentiation of rat BMSCs into SCLCs and to explore their potential mechanisms. BMSCs were induced using two distinct methods: a composite factor induction approach (Protocol-1) and a conditioned culture medium induction approach (Protocol-2). The expression of Schwann cells (SCs) marker proteins and neurotrophic factors (NTFs) in the differentiated cells was assessed. Cell proliferation and apoptosis were also measured. During induction, changes in miR-21 and Sprouty RTK signaling antagonist 2 (SPRY2) mRNA were analyzed. Following the transfection of BMSCs with miR-21 agomir or miR-21 antagomir, induction was carried out using both protocols, and the expression of SPRY2, ERK1/2, and SCs marker proteins was examined. The results revealed that NTFs expression was higher in Protocol-1, whereas SCs marker proteins expression did not significantly differ between the two groups. Compared to Protocol-1, Protocol-2 exhibited enhanced cell proliferation and fewer apoptotic and necrotic cells. Both protocols showed a negative correlation between miR-21 and SPRY2 expression throughout the induction stages. After induction, the miR-21 agomir group exhibited reduced SPRY2 expression, increased ERK1/2 expression, and significantly elevated expression of SCs marker proteins. This study demonstrates that Protocol-1 yields higher NTFs expression, whereas Protocol-2 results in stronger SCLCs proliferation. Upregulating miR-21 suppresses SPRY2 expression, activates the ERK1/2 signaling pathway, and promotes BMSC differentiation into SCLCs.","PeriodicalId":22131,"journal":{"name":"Synapse","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082405","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}

引用次数: 0

Time of day does not impact spinal serotonin levels in humans. 一天中的任何时间都不会影响人体脊髓血清素的水平。

IF 2.3 4区医学

Synapse Pub Date : 2024-05-01 DOI: 10.1002/syn.22291

Sharath Kumar Anand, Raj S Lavadi, Benjamin R Johnston, Joshua I Chalif, James M Scanlon, Weiwen Wang, Nitin Agarwal, David K Hamilton, Daryl P Fields, Clinton W Van't Land

{"title":"Time of day does not impact spinal serotonin levels in humans.","authors":"Sharath Kumar Anand, Raj S Lavadi, Benjamin R Johnston, Joshua I Chalif, James M Scanlon, Weiwen Wang, Nitin Agarwal, David K Hamilton, Daryl P Fields, Clinton W Van't Land","doi":"10.1002/syn.22291","DOIUrl":"https://doi.org/10.1002/syn.22291","url":null,"abstract":"Spinal serotonin enables neuro-motor recovery (i.e., plasticity) in patients with debilitating paralysis. While there exists time of day fluctuations in serotonin-dependent spinal plasticity, it is unknown, in humans, whether this is due to dynamic changes in spinal serotonin levels or downstream signaling processes. The primary objective of this study was to determine if time of day variations in spinal serotonin levels exists in humans. To assess this, intrathecal drains were placed in seven adults with cerebrospinal fluid (CSF) collected at diurnal (05:00 to 07:00) and nocturnal (17:00 to 19:00) intervals. High performance liquid chromatography with mass spectrometry was used to quantify CSF serotonin levels with comparisons being made using univariate analysis. From the 7 adult patients, 21 distinct CSF samples were collected: 9 during the diurnal interval and 12 during nocturnal. Diurnal CSF samples demonstrated an average serotonin level of 216.6 <math><semantics><mo>±</mo> <annotation>$ pm $</annotation></semantics> </math> 67.7 nM. Nocturnal CSF samples demonstrated an average serotonin level of 206.7 <math><semantics><mo>±</mo> <annotation>$ pm $</annotation></semantics> </math> 75.8 nM. There was no significant difference between diurnal and nocturnal CSF serotonin levels (p = .762). Within this small cohort of spine healthy adults, there were no differences in diurnal versus nocturnal spinal serotonin levels. These observations exclude spinal serotonin levels as the etiology for time of day fluctuations in serotonin-dependent spinal plasticity expression.","PeriodicalId":22131,"journal":{"name":"Synapse","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908808","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}

引用次数: 0

Role of M₄ -receptor cholinergic signaling in direct pathway striatal projection neurons during dopamine depletion. 多巴胺耗竭时 M4 - 受体胆碱能信号在直接通路纹状体投射神经元中的作用

IF 2.3 4区医学

Synapse Pub Date : 2024-03-01 DOI: 10.1002/syn.22287

Avilés-Rosas Vh, Rendón-Ochoa Ea, Hernández-Flores T, Flores-León M, Arias C, Galarraga E, Bargas J

{"title":"Role of M4 -receptor cholinergic signaling in direct pathway striatal projection neurons during dopamine depletion.","authors":"Avilés-Rosas Vh, Rendón-Ochoa Ea, Hernández-Flores T, Flores-León M, Arias C, Galarraga E, Bargas J","doi":"10.1002/syn.22287","DOIUrl":"10.1002/syn.22287","url":null,"abstract":"Direct pathway striatal projection neurons (dSPNs) are characterized by the expression of dopamine (DA) class 1 receptors (D1 R), as well as cholinergic muscarinic M1 and M4 receptors (M1 R, M4 R). D1 R enhances neuronal firing through phosphorylation of voltage-gate calcium channels (CaV 1 Ca2+ channels) activating Gs proteins and protein kinase A (PKA). Concurrently, PKA suppresses phosphatase PP-1 through DARPP-32, thus extending this facilitatory modulation. M1 R also influences Ca2+ channels in SPNs through Gq proteins and protein kinase C. However, the signaling mechanisms of M4 R in dSPNs are less understood. Two pathways are attributed to M4 R: an inhibitory one through Gi/o proteins, and a facilitatory one via the cyclin Cdk5. Our study reveals that a previously observed facilitatory modulation via CaV 1 Ca2+ channels is linked to the Cdk5 pathway in dSPNs. This result could be significant in treating parkinsonism. Therefore, we questioned whether this effect persists post DA-depletion in experimental parkinsonism. Our findings indicate that in such conditions, M4 R activation leads to a decrease in Ca2+ current and an increased M4 R protein level, contrasting with the control response. Nevertheless, parkinsonian and control actions are inhibited by the Cdk5 inhibitor roscovitine, suggesting Cdk5's role in both conditions. Cdk5 may activate PP-1 via PKA inhibition in DA depletion. Indeed, we found that inhibiting PP-1 restores control M4 R actions, implying that PP-1 is overly active via M4 Rs in DA-depleted condition. These insights contribute to understanding how DA-depletion alters modulatory signaling in striatal neurons. Additional working hypotheses are discussed.","PeriodicalId":22131,"journal":{"name":"Synapse","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139997481","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}

引用次数: 0

IF 2.3 4区医学

Synapse Pub Date : 2024-03-01 DOI: 10.1002/syn.22289

Züleyha Doğanyiğit, Aslı Okan, Seher Yılmaz, A Cihangir Uğuz, Enes Akyüz

{"title":"Gender-related variation expressions of neuroplastin TRAF6, GluA1, GABA(A) receptor, and PMCA in cortex, hippocampus, and brainstem in an experimental epilepsy model.","authors":"Züleyha Doğanyiğit, Aslı Okan, Seher Yılmaz, A Cihangir Uğuz, Enes Akyüz","doi":"10.1002/syn.22289","DOIUrl":"10.1002/syn.22289","url":null,"abstract":"Epileptic seizures are seen as a result of changing excitability balance depending on the deterioration in synaptic plasticity in the brain. Neuroplastin, and its related molecules which are known to play a role in synaptic plasticity, neurotransmitter activities that provide balance of excitability and, different neurological diseases, have not been studied before in epilepsy. In this study, a total of 34 Sprague-Dawley male and female rats, 2 months old, weighing 250-300 g were used. The epilepsy model in rats was made via pentylenetetrazole (PTZ). After the completion of the experimental procedure, the brain tissue of the rats were taken and the histopathological changes in the hippocampus and cortex parts and the brain stem were investigated, as well as the immunoreactivity of the proteins related to the immunohistochemical methods. As a result of the histopathological evaluation, it was determined that neuron degeneration and the number of dilated blood vessels in the hippocampus, frontal cortex, and brain stem were higher in the PTZ status epilepticus (SE) groups than in the control groups. It was observed that neuroplastin and related proteins TNF receptor-associated factor 6 (TRAF6), Gamma amino butyric acid type A receptors [(GABA(A)], and plasma membrane Ca2+ ATPase (PMCA) protein immunoreactivity levels increased especially in the male hippocampus, and only AMPA receptor subunit type 1 (GluA1) immunoreactivity decreased, unlike other proteins. We believe this may be caused by a problem in the mechanisms regulating the interaction of neuroplastin and GluA1 and may cause problems in synaptic plasticity in the experimental epilepsy model. It may be useful to elucidate this mechanism and target GluA1 when determining treatment strategies.","PeriodicalId":22131,"journal":{"name":"Synapse","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022656","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}

引用次数: 0

Liproxstatin-1 alleviates ferroptosis in sevoflurane anesthesia-induced cognitive deficits of aged mice: The role oxidative stress 脂氧司他丁-1能缓解七氟醚麻醉诱导的老年小鼠认知缺陷中的铁蛋白沉积：氧化应激的作用

IF 2.3 4区医学

Synapse Pub Date : 2024-01-15 DOI: 10.1002/syn.22286

Shunyuan Li, Yingle Chen, Yingmei Wang, Xianmei Zhong, Xiaoquan Yu, Zhenming Kang, Yangyi Li

{"title":"Liproxstatin-1 alleviates ferroptosis in sevoflurane anesthesia-induced cognitive deficits of aged mice: The role oxidative stress","authors":"Shunyuan Li, Yingle Chen, Yingmei Wang, Xianmei Zhong, Xiaoquan Yu, Zhenming Kang, Yangyi Li","doi":"10.1002/syn.22286","DOIUrl":"https://doi.org/10.1002/syn.22286","url":null,"abstract":"In this study, we aimed to validate the hypothesis that the interplay between sevoflurane, oxidative stress and ferroptosis is crucial for the pathogenesis of sevoflurane-induced cognitive impairment in aged individuals. The mice with sevoflurane-induced cognitive impairment were used to explore the effects of sevoflurane on oxidative stress, iron homeostasis, and cognitive function in aged mice. Iron content and oxidative stress markers were analyzed in hippocampal tissue homogenates using specific assays. Additionally, the levels of iron death-related markers (Fth1 and Gpx4) were assessed by real-time PCR and Western blotting. Morris Water Maze and novel object recognition (NOR) tests were conducted to evaluate cognitive function. Sevoflurane exposure in aged mice resulted in a significant increase in iron overloading in the hippocampus, followed by a subsequent stabilization. Oxidative stress levels were elevated in the hippocampal tissue of sevoflurane-exposed mice, and a significant correlation was observed between iron death and oxidative stress. Liproxstatin-1, a ferroptosis inhibitor, effectively ameliorated the decline in memory and learning abilities induced by sevoflurane anesthesia. Liproxstatin-1 treatment reduced iron overload and oxidative stress in the hippocampal tissue of aged mice. The expression of Fth1 and Gpx4, iron death-related markers, was downregulated following Liproxstatin-1 intervention. Our findings suggest that sevoflurane anesthesia disrupts iron homeostasis, leading to increased oxidative stress and cognitive impairment in aged mice. These results highlight the potential of targeting iron-mediated processes to mitigate sevoflurane-induced cognitive impairment in the aging population.","PeriodicalId":22131,"journal":{"name":"Synapse","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139475917","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}

引用次数: 0