NeuroMolecular Medicine最新文献_第7页

Inhibition of CRMP2 Phosphorylation Suppresses Microglia Activation in the Retina and Optic Nerve and Promotes Optic Nerve Regeneration After Optic Nerve Injury 抑制 CRMP2 磷酸化可抑制视网膜和视神经中的小胶质细胞活化并促进视神经损伤后的视神经再生

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-09-12 DOI: 10.1007/s12017-024-08805-1

Yuebing Wang, Sayaka Harada, Yoshio Goshima, Toshio Ohshima

{"title":"Inhibition of CRMP2 Phosphorylation Suppresses Microglia Activation in the Retina and Optic Nerve and Promotes Optic Nerve Regeneration After Optic Nerve Injury","authors":"Yuebing Wang, Sayaka Harada, Yoshio Goshima, Toshio Ohshima","doi":"10.1007/s12017-024-08805-1","DOIUrl":"https://doi.org/10.1007/s12017-024-08805-1","url":null,"abstract":"As the primary connection between the eye and brain, the optic nerve plays a pivotal role in visual information transmission. Injuries to the optic nerve can occur for various reasons, including trauma, glaucoma, and neurodegenerative diseases. Retinal ganglion cells (RGCs), a type of neurons that extend axons through the optic nerve, can rapidly respond to injury and initiate cell death. Additionally, following optic nerve injury microglia, which serve as markers of neuroinflammation, transition from a resting state to an activated state. The phosphorylation of collapsin response mediator protein2 (CRMP2) in the semaphorin 3A (Sema3A) signalling pathway affects several processes, including axon guidance and neuron regeneration. In this study, we used an optic nerve crush (ONC) mouse model to investigate the effects of suppressing CRMP2 phosphorylation on microglia activation. We found that CRMP2 phosphorylation inhibitor suppressed RGCs loss and promoted neuronal regeneration following ONC. In addition, CRMP2 S522A mutant (CRMP2 KI) mice exhibited decreased microglial activation in both the retina and optic nerve following ONC. These results suggest that inhibiting the phosphorylation of CRMP2 can alleviate the loss of RGCs and microglial activation after optic nerve injury, providing insight into the development of treatments for optical neuropathies and neurodegenerative diseases.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"29 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142218922","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

Dysregulated Purinergic Signalling in Fragile X Syndrome Cortical Astrocytes 脆性 X 综合征皮质星形胶质细胞的嘌呤能信号失调

IF 3.5 4区医学

NeuroMolecular Medicine Pub Date : 2024-09-10 DOI: 10.1007/s12017-024-08802-4

Kathryn E. Reynolds, Matthew Napier, Fan Fei, Kirk Green, Angela L. Scott

{"title":"Dysregulated Purinergic Signalling in Fragile X Syndrome Cortical Astrocytes","authors":"Kathryn E. Reynolds, Matthew Napier, Fan Fei, Kirk Green, Angela L. Scott","doi":"10.1007/s12017-024-08802-4","DOIUrl":"https://doi.org/10.1007/s12017-024-08802-4","url":null,"abstract":"The symptoms of fragile X syndrome (FXS), caused by a single gene mutation to Fmr1, have been increasingly linked to disordered astrocyte signalling within the cerebral cortex. We have recently demonstrated that the purinergic signalling pathway, which utilizes nucleoside triphosphates and their metabolites to facilitate bidirectional glial and glial-neuronal interactions, is upregulated in cortical astrocytes derived from the Fmr1 knockout (KO) mouse model of FXS. Heightened Fmr1 KO P2Y purinergic receptor levels were correlated with prolonged intracellular calcium release, elevated synaptogenic protein secretion, and hyperactivity of developing circuits. However, due to the relative lack of sensitive and reproducible quantification methods available for measuring purines and pyrimidines, determining the abundance of these factors in Fmr1 KO astrocytes was limited. We therefore developed a hydrophilic interaction liquid chromatography protocol coupled with mass spectrometry to compare the abundance of intracellular and extracellular purinergic molecules between wildtype and Fmr1 KO mouse astrocytes. Significant differences in the concentrations of UDP, ATP, AMP, and adenosine intracellular stores were found within Fmr1 KO astrocytes relative to WT. The extracellular level of adenosine was also significantly elevated in Fmr1 KO astrocyte-conditioned media in comparison to media collected from WT astrocytes. Glycosylation of the astrocyte membrane-bound CD39 ectonucleotidase, which facilitates ligand breakdown following synaptic release, was also elevated in Fmr1 KO astrocyte cultures. Together, these differences demonstrated further dysregulation of the purinergic signalling system within Fmr1 KO cortical astrocytes, potentially leading to significant alterations in FXS purinergic receptor activation and cellular pathology.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"1 1","pages":"36"},"PeriodicalIF":3.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142218887","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

Neuroprotective Effects of VGLUT1 Inhibition in HT22 Cells Overexpressing VGLUT1 Under Oxygen Glucose Deprivation Conditions. 在缺氧缺糖条件下抑制 VGLUT1 对过表达 VGLUT1 的 HT22 细胞的神经保护作用

IF 3.3 4区医学

NeuroMolecular Medicine Pub Date : 2024-08-23 DOI: 10.1007/s12017-024-08803-3

B Pomierny, W Krzyżanowska, A Skórkowska, B Budziszewska, J Pera

{"title":"Neuroprotective Effects of VGLUT1 Inhibition in HT22 Cells Overexpressing VGLUT1 Under Oxygen Glucose Deprivation Conditions.","authors":"B Pomierny, W Krzyżanowska, A Skórkowska, B Budziszewska, J Pera","doi":"10.1007/s12017-024-08803-3","DOIUrl":"10.1007/s12017-024-08803-3","url":null,"abstract":"Glutamate (Glu) is a major excitatory neurotransmitter in the brain, essential for synaptic plasticity, neuronal activity, and memory formation. However, its dysregulation leads to excitotoxicity, implicated in neurodegenerative diseases and brain ischemia. Vesicular glutamate transporters (VGLUTs) regulate Glu loading into synaptic vesicles, crucial for maintaining optimal extracellular Glu levels. This study investigates the neuroprotective effects of VGLUT1 inhibition in HT22 cells overexpressing VGLUT1 under oxygen glucose deprivation (OGD) conditions. HT22 cells, a hippocampal neuron model, were transduced with lentiviral vectors to overexpress VGLUT1. Cells were subjected to OGD, with pre-incubation of Chicago Sky Blue 6B (CSB6B), an unspecific VGLUT inhibitor. Cell viability, lactate dehydrogenase (LDH) release, mitochondrial membrane potential, and hypoxia-related protein markers (PARP1, AIF, NLRP3) were assessed. Results indicated that VGLUT1 overexpression increased vulnerability to OGD, evidenced by higher LDH release and reduced cell viability. CSB6B treatment improved cell viability and reduced LDH release in OGD conditions, particularly at 0.1 μM and 1.0 μM concentrations. Moreover, CSB6B preserved mitochondrial membrane potential and decreased levels of PARP1, AIF, and NLRP3 proteins, suggesting neuroprotective effects through mitigating excitotoxicity. This study demonstrates that VGLUT1 inhibition could be a promising therapeutic strategy for ischemic brain injury, warranting further investigation into selective VGLUT1 inhibitors.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"26 1","pages":"35"},"PeriodicalIF":3.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exosomal GDNF from Bone Marrow Mesenchymal Stem Cells Moderates Neuropathic Pain in a Rat Model of Chronic Constriction Injury. 骨髓间充质干细胞外泌 GDNF 可缓和大鼠慢性收缩性损伤模型中的神经性疼痛

IF 3.3 4区医学

NeuroMolecular Medicine Pub Date : 2024-08-21 DOI: 10.1007/s12017-024-08800-6

Xuelei Zhang, Huan Liu, Xiaolei Xiu, Jibo Cheng, Tong Li, Ping Wang, Lili Men, Junru Qiu, Yanyan Jin, Jianyong Zhao

{"title":"Exosomal GDNF from Bone Marrow Mesenchymal Stem Cells Moderates Neuropathic Pain in a Rat Model of Chronic Constriction Injury.","authors":"Xuelei Zhang, Huan Liu, Xiaolei Xiu, Jibo Cheng, Tong Li, Ping Wang, Lili Men, Junru Qiu, Yanyan Jin, Jianyong Zhao","doi":"10.1007/s12017-024-08800-6","DOIUrl":"10.1007/s12017-024-08800-6","url":null,"abstract":"Both of exosomes derived from mesenchymal stem cells (MSCs) and glial cell line-derived neurotrophic factor (GDNF) show potential for the treatment of neuropathic pain. Here, the analgesic effects of exosomes derived from bone marrow MSCs (BMSCs) were investigated. BMSCs-derived exosomes were isolated and characterized. Chronic constriction injury (CCI) was constructed to induce neuropathic pain in rats, which were then treated with exosomes. Pain behaviors were evaluated by measuring paw withdrawal thresholds and latency. The changes of key proteins, including cytokines, were explored using Western blot and ELISA. Administration of BMSCs-derived exosomes alleviated neuropathic pain, as demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia, as well as the reduced secretion of pro-inflammatory cytokines in CCI rats. These effects were comparable to the treatment of GDNF alone. Mechanically, the exosomes suppressed the CCI-induced activation of TLR2/MyD88/NF-κB signaling pathway, while GDNF knockdown impaired their analgesic effects on CCI rat. BMSCs-derived exosomes may alleviate CCI-induced neuropathic pain and inflammation in rats by transporting GDNF.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"26 1","pages":"34"},"PeriodicalIF":3.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018169","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

Activation of GPR30 Ameliorates Cerebral Ischemia-Reperfusion Injury by Suppressing Ferroptosis Through Nrf2/GPX4 Signaling Pathway. 激活 GPR30 可通过 Nrf2/GPX4 信号通路抑制铁凋亡，从而改善脑缺血再灌注损伤

IF 3.3 4区医学

NeuroMolecular Medicine Pub Date : 2024-08-13 DOI: 10.1007/s12017-024-08801-5

Yong-Qiang Zhang, Ting Sun, Zhen Zhao, Jing Fu, Le Yang, Yuan Xu, Jing-Feng Zhao, Xiu-Ling Tang, An Liu, Ming-Gao Zhao

{"title":"Activation of GPR30 Ameliorates Cerebral Ischemia-Reperfusion Injury by Suppressing Ferroptosis Through Nrf2/GPX4 Signaling Pathway.","authors":"Yong-Qiang Zhang, Ting Sun, Zhen Zhao, Jing Fu, Le Yang, Yuan Xu, Jing-Feng Zhao, Xiu-Ling Tang, An Liu, Ming-Gao Zhao","doi":"10.1007/s12017-024-08801-5","DOIUrl":"10.1007/s12017-024-08801-5","url":null,"abstract":"The newly identified estrogen receptor, G protein-coupled receptor 30 (GPR30), is prevalent in the brain and has been shown to provide significant neuroprotection. Recent studies have linked ferroptosis, a newly characterized form of programmed cell death, closely with cerebral ischemia-reperfusion injury (CIRI), highlighting it as a major contributing factor. Consequently, our research aimed to explore the potential of GPR30 targeting in controlling neuronal ferroptosis and lessening CIRI impacts. Results indicated that GPR30 activation not only improved neurological outcomes and decreased infarct size in a mouse model but also lessened iron accumulation and malondialdehyde formation post-middle cerebral artery occlusion (MCAO). This protective effect extended to increased levels of Nrf2 and GPX4 proteins. Similar protective results were replicated in PC12 cells subjected to Oxygen Glucose Deprivation and Reoxygenation (OGD/R) using the GPR30-specific agonist G1. Importantly, inhibition of Nrf2 with ML385 curtailed the neuroprotective effects of GPR30 activation, suggesting that GPR30 mitigates CIRI primarily through inhibition of neuronal ferroptosis via upregulation of Nrf2 and GPX4.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"26 1","pages":"33"},"PeriodicalIF":3.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976253","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

Evaluation of Neuroprotective Effect of Gut Microbe in Parkinson's Disease: An In Silico and In Vivo Approach. 评估肠道微生物对帕金森病的神经保护作用：体内和体外方法。

IF 3.3 4区医学

NeuroMolecular Medicine Pub Date : 2024-08-01 DOI: 10.1007/s12017-024-08799-w

Kanika Bhardwaj, Neelu Kanwar Rajawat, Nupur Mathur, Aviral Kaushik

{"title":"Evaluation of Neuroprotective Effect of Gut Microbe in Parkinson's Disease: An In Silico and In Vivo Approach.","authors":"Kanika Bhardwaj, Neelu Kanwar Rajawat, Nupur Mathur, Aviral Kaushik","doi":"10.1007/s12017-024-08799-w","DOIUrl":"10.1007/s12017-024-08799-w","url":null,"abstract":"Parkinson's disease is a progressive neurodegenerative disorder marked by the death of dopaminergic neurons in the substantia nigra region of the brain. Aggregation of alpha-synuclein (α-synuclein) is a contributing factor to Parkinson's disease pathogenesis. The objective of this study is to investigate the neuroprotective effects of gut microbes on α-synuclein aggregation using both in silico and in vivo approaches. We focussed on the interaction between α-synuclein and metabolites released by gut bacteria that protect from PD. We employed three probiotic microbe strains against α-synuclein protein: Lactobacillus casei, Escherichia coli, and Bacillus subtilis, with their chosen PDB IDs being Dihydrofolate reductase (3DFR), methionine synthetase (6BM5), and tryptophanyl-tRNA synthetase (3PRH), respectively. Using HEX Dock 6.0 software, we examined the interactions between these proteins. Among the various metabolites, methionine synthetase produced by E. coli showed potential interactions with α-synuclein. To further evaluate the neuroprotective benefits of E. coli, an in vivo investigation was performed using a rotenone-induced Parkinsonian mouse model. The motor function of the animals was assessed through behavioural tests, and oxidative stress and neurotransmitter levels were also examined. The results demonstrated that, compared to the rotenone-induced PD mouse model, the rate of neurodegeneration was considerably reduced in mice treated with E. coli. Additionally, histopathological studies provided evidence of the neuroprotective effects of E. coli. In conclusion, this study lays the groundwork for future research, suggesting that gut bacteria may serve as potential therapeutic agents in the development of medications to treat Parkinson's disease. fig. 1.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"26 1","pages":"32"},"PeriodicalIF":3.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875518","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

Physical Exercise Inhibits Cognitive Impairment and Memory Loss in Aged Mice, and Enhances Pre- and Post-Synaptic Proteins in the Hippocampus of Young and Aged Mice. 体育锻炼可抑制老年小鼠的认知障碍和记忆丧失，并增强年轻小鼠和老年小鼠海马突触前后蛋白的功能

IF 3.3 4区医学

NeuroMolecular Medicine Pub Date : 2024-07-29 DOI: 10.1007/s12017-024-08798-x

Ricardo Augusto Leoni De Sousa, Caique Olegário Diniz-Magalhaes, Poliany Pereira Cruz, Gustavo Henrique Bahia de Oliveira, Julia Tereza Aparecida Caldeira Prates, Crisley Mara de Azevedo Ferreira, Rosiane Rosa Silva, Ricardo Cardoso Cassilhas

{"title":"Physical Exercise Inhibits Cognitive Impairment and Memory Loss in Aged Mice, and Enhances Pre- and Post-Synaptic Proteins in the Hippocampus of Young and Aged Mice.","authors":"Ricardo Augusto Leoni De Sousa, Caique Olegário Diniz-Magalhaes, Poliany Pereira Cruz, Gustavo Henrique Bahia de Oliveira, Julia Tereza Aparecida Caldeira Prates, Crisley Mara de Azevedo Ferreira, Rosiane Rosa Silva, Ricardo Cardoso Cassilhas","doi":"10.1007/s12017-024-08798-x","DOIUrl":"10.1007/s12017-024-08798-x","url":null,"abstract":"The aim of this study was to evaluate the effects of swimming in the brain and behavior of young and aged mice. Forty-eight male C57BL/6 J mice were randomly distributed into 4 groups (n = 12 per group, 3 and 18 months old). The subdivision of the groups was: 3 months-SED, 18 months-SED, 3 months-EXE, and 18 months-EXE. SED mice did not swim, while EXE mice performed the physical exercise protocol. Training was initiated 48 h after the adaptation week. Swimming sessions consisted of 30 min, with no overload, 5 days per week, for 4 weeks. After the exercise protocol, it was revealed working and spatial memory were impaired in the 18 months-SED group. Pre- and post-synaptic proteins were enhanced in the groups that swam when compared to the 3- and 8 months-SED groups. Lipid peroxidation was greater in the aged mice that did not perform the physical exercise protocol and might have contributed to the cognitive impairment in this group. In conclusion, an aerobic physical exercise protocol, performed through regular swimming sessions, inhibited cognitive impairment, memory loss and lipid peroxidation in the aged mice, while pre- and post-synaptic proteins were enhanced in the hippocampus of young and aged mice.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"26 1","pages":"31"},"PeriodicalIF":3.3,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788752","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

The CD44s Isoform is a Potential Biomarker for Predicting Craniopharyngioma Recurrence in Children. CD44s异构体是预测儿童颅咽管瘤复发的潜在生物标记物

IF 3.3 4区医学

NeuroMolecular Medicine Pub Date : 2024-07-17 DOI: 10.1007/s12017-024-08797-y

K Bajdak-Rusinek, N Diak, E Gutmajster, A Fus-Kujawa, M Ciupińska, B Kalina-Faska, A Trybus, M Grajek, M Kalina, M Mandera

{"title":"The CD44s Isoform is a Potential Biomarker for Predicting Craniopharyngioma Recurrence in Children.","authors":"K Bajdak-Rusinek, N Diak, E Gutmajster, A Fus-Kujawa, M Ciupińska, B Kalina-Faska, A Trybus, M Grajek, M Kalina, M Mandera","doi":"10.1007/s12017-024-08797-y","DOIUrl":"10.1007/s12017-024-08797-y","url":null,"abstract":"Adamantinomatous craniopharyngioma (ACP) is an intracranial tumor considered partly malignant due to its ability to infiltrate surrounding structures and tendency to relapse despite radical resection. CD44 is a known stem cell marker in ACP and is upregulated in cell clusters of invasive ACP protrusions; however, the functions of its alternative splicing isoform variants, CD44s and CD44v1-10, have not yet been studied in terms of ACP recurrence, despite their confirmed roles in cancer development and progression. In this study, we first confirmed the difference in total CD44 expression between samples from patients who experienced relapse and those from patients who did not. Moreover, our findings showed that, in recurrent samples, the predominant isoform expressed was CD44s, which might indicate its significance in predicting ACP recurrence. The association between increased CD44 expression and recurrence may lead to the development of prognostic markers of ACP aggressiveness and relapse potential; however, further studies are needed to clarify the exact mechanism of CD44 expression.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"26 1","pages":"30"},"PeriodicalIF":3.3,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11254967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Astaxanthin Rescues Memory Impairments in Rats with Vascular Dementia by Protecting Against Neuronal Death in the Hippocampus. 虾青素通过防止海马区神经元死亡修复血管性痴呆大鼠的记忆损伤

IF 3.3 4区医学

NeuroMolecular Medicine Pub Date : 2024-07-16 DOI: 10.1007/s12017-024-08796-z

Na Wei, Luo-Man Zhang, Jing-Jing Xu, Sheng-Lei Li, Rui Xue, Sheng-Li Ma, Cai Li, Miao-Miao Sun, Kui-Sheng Chen

{"title":"Astaxanthin Rescues Memory Impairments in Rats with Vascular Dementia by Protecting Against Neuronal Death in the Hippocampus.","authors":"Na Wei, Luo-Man Zhang, Jing-Jing Xu, Sheng-Lei Li, Rui Xue, Sheng-Li Ma, Cai Li, Miao-Miao Sun, Kui-Sheng Chen","doi":"10.1007/s12017-024-08796-z","DOIUrl":"10.1007/s12017-024-08796-z","url":null,"abstract":"Vascular dementia (VaD) is a cognitive disorder characterized by a decline in cognitive function resulting from cerebrovascular disease. The hippocampus is particularly susceptible to ischemic insults, leading to memory deficits in VaD. Astaxanthin (AST) has shown potential therapeutic effects in neurodegenerative diseases. However, the mechanisms underlying its protective effects in VaD and against hippocampal neuronal death remain unclear. In this study, We used the bilateral common carotid artery occlusion (BCCAO) method to establish a chronic cerebral hypoperfusion (CCH) rat model of VaD and administered a gastric infusion of AST at 25 mg/kg per day for 4 weeks to explore its therapeutic effects. Memory impairments were assessed using Y-maze and Morris water maze tests. We also performed biochemical analyses to evaluate levels of hippocampal neuronal death and apoptosis-related proteins, as well as the impact of astaxanthin on the PI3K/Akt/mTOR pathway and oxidative stress. Our results demonstrated that AST significantly rescued memory impairments in VaD rats. Furthermore, astaxanthin treatment protected against hippocampal neuronal death and attenuated apoptosis. We also observed that AST modulated the PI3K/Akt/mTOR pathway, suggesting its involvement in promoting neuronal survival and synaptic plasticity. Additionally, AST exhibited antioxidant properties, mitigating oxidative stress in the hippocampus. These findings provide valuable insights into the potential therapeutic effects of AST in VaD. By elucidating the mechanisms underlying the actions of AST, this study highlights the importance of protecting hippocampal neurons and suggests potential targets for intervention in VaD. There are still some unanswered questions include long-term effects and optimal dosage of the use in human. Further research is warranted to fully understand the therapeutic potential of AST and its application in the clinical treatment of VaD.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"26 1","pages":"29"},"PeriodicalIF":3.3,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627174","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

A Comprehensive Overview of NF1 Mutations in Iranian Patients. 伊朗患者 NF1 基因突变综述

IF 3.3 4区医学

NeuroMolecular Medicine Pub Date : 2024-07-02 DOI: 10.1007/s12017-024-08790-5

Shahram Savad, Mohammad-Hossein Modarressi, Sarang Younesi, Mahnaz Seifi-Alan, Niusha Samadaian, Mona Masoomy, Mehdi Dianatpour, Shima Norouzi, Saloomeh Amidi, Amirreza Boroumand, Mahmoud Reza Ashrafi, Alireza Ronagh, Maryam Eslami, Maryam Hashemnejad, Shahab Nourian, Sanaz Mohammadi, Mohammad Mahdi Taheri Amin, Morteza Heidari, Mahin Seifi-Alan, Hossein Shojaaldini Ardakani, Fatemeh Aghamahdi, Sheyda Khalilian, Soudeh Ghafouri-Fard

{"title":"A Comprehensive Overview of NF1 Mutations in Iranian Patients.","authors":"Shahram Savad, Mohammad-Hossein Modarressi, Sarang Younesi, Mahnaz Seifi-Alan, Niusha Samadaian, Mona Masoomy, Mehdi Dianatpour, Shima Norouzi, Saloomeh Amidi, Amirreza Boroumand, Mahmoud Reza Ashrafi, Alireza Ronagh, Maryam Eslami, Maryam Hashemnejad, Shahab Nourian, Sanaz Mohammadi, Mohammad Mahdi Taheri Amin, Morteza Heidari, Mahin Seifi-Alan, Hossein Shojaaldini Ardakani, Fatemeh Aghamahdi, Sheyda Khalilian, Soudeh Ghafouri-Fard","doi":"10.1007/s12017-024-08790-5","DOIUrl":"10.1007/s12017-024-08790-5","url":null,"abstract":"Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in the NF1 gene. This disorder shows nearly complete penetrance and high phenotypic variability. We used the whole-exome sequencing technique to identify mutations in 32 NF1 cases from 22 Iranian families. A total of 31 variants, including 30 point mutations and one large deletion, were detected. In eight cases, variants were inherited, while they were sporadic in the remaining. Seven novel variants, including c.5576 T > G, c.6658_6659insC, c.2322dupT, c.92_93insAA, c.4360C > T, c.3814C > T, and c.4565_4566delinsC, were identified. The current study is the largest in terms of the sample size of Iranian NF1 cases with identified mutations. The results can broaden the spectrum of NF1 mutations and facilitate the process of genetic counseling in the affected families.","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"26 1","pages":"28"},"PeriodicalIF":3.3,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492853","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