NeuroMolecular Medicine最新文献

{"title":"Multiplex Analysis of Cerebrospinal Fluid and Serum Exosomes MicroRNAs of Untreated Relapsing Remitting Multiple Sclerosis (RRMS) and Proposing Noninvasive Diagnostic Biomarkers.","authors":"Mina Mohammadinasr,&nbsp;Soheila Montazersaheb,&nbsp;Ommoleila Molavi,&nbsp;Houman Kahroba,&nbsp;Mahnaz Talebi,&nbsp;Hormoz Ayromlou,&nbsp;Mohammad Saeid Hejazi","doi":"10.1007/s12017-023-08744-3","DOIUrl":"10.1007/s12017-023-08744-3","url":null,"abstract":"<p><p>Exosomal microRNAs (miRNAs) are emerging diagnostic biomarkers for neurodegenerative diseases. In this study, we aimed to detect relapsing-remitting multiple sclerosis (RRMS)-specific miRNAs in cerebrospinal fluid (CSF) and serum exosomes with diagnostic potential. One ml of CSF and serum sample were collected from each of the 30 untreated RRMS patients and healthy controls (HCs). A panel of 18 miRNAs affecting inflammatory responses was applied, and qRT-PCR was conducted to detect differentially expressed exosomal miRNAs in CSF and serum of RRMS patients. We identified that 17 out of 18 miRNAs displayed different patterns in RRMS patients compared to HCs. Let-7 g-5p, miR-18a-5p, miR-145-5p, and miR-374a-5p with dual pro-inflammatory and anti-inflammatory actions and miR-150-5p and miR-342-3p with anti-inflammatory action were significantly upregulated in both CSF and serum-derived exosomes of RRMS patients compared to corresponding HCs. Additionally, anti-inflammatory miR-132-5p and pro-inflammatory miR-320a-5p were significantly downregulated in both CSF and serum-derived exosomes of RRMS patients compared to HCs. Ten of 18 miRNAs were differentially expressed in CSF and serum exosomes of the patients. Furthermore, miR-15a-5p, miR-19b-3p, and miR-432-5p were upregulated, and miR-17-5p was downregulated only in CSF exosomes. Interestingly, U6 housekeeping gene was differentially expressed in CSF and serum exosomes, in both RRMS and HCs. As the first report describing CSF exosomal miRNAs expression profile compared to that of serum exosomes in untreated RRMS patients, we showed that CSF and serum exosomes are not identical in terms of biological compounds and display different patterns in miRNAs and U6 expression.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":" ","pages":"402-414"},"PeriodicalIF":3.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9621956","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}

{"title":"Dimethyl Itaconate Reduces Cognitive Impairment and Neuroinflammation in APPswe/PS1ΔE9 Transgenic Mouse Model of Alzheimer's Disease.","authors":"Jing Xiong,&nbsp;Dong-Lin Lu,&nbsp;Bai-Qiang Chen,&nbsp;Tong-Yun Liu,&nbsp;Zi-Xuan Wang","doi":"10.1007/s12017-022-08725-y","DOIUrl":"https://doi.org/10.1007/s12017-022-08725-y","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common type of dementia characterized by abnormal accumulation of amyloid-β (Aβ) plaques, neuroinflammation, and neuronal loss. Dimethyl itaconate (DI), a membrane-permeable derivative of itaconate, has been recently reported to limit inflammation. However, the effect of DI in the APPswe/PS1ΔE9 (APP/PS1) transgenic mouse model of AD remains unclear. We treated APP/PS1 mice with DI or saline. Our results showed that DI ameliorated the cognitive deficits of APP/PS1 mice. Further, DI significantly decreased brain Aβ deposition and Aβ levels, inhibited cell apoptosis, decreased hippocampal and cortical neuronal damage. We also found that DI promoted the expression of the Nrf2/HO-1 signaling pathway, while inhibited cognitive impairment, cell apoptosis, and the proinflammatory cytokine levels in the brains of APP/PS1 mice. Our results indicated that DI attenuated memory impairment and neuroinflammation via the Nrf2 signaling pathway in APP/PS1 mice, suggesting that DI might be recognized as a promising candidate for the treatment of AD.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"25 2","pages":"179-192"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9682931","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}

{"title":"Therapeutic Potential of Quercetin and its Derivatives in Epilepsy: Evidence from Preclinical Studies.","authors":"Chandra Prakash,&nbsp;Jyoti Tyagi,&nbsp;Shyam Sunder Rabidas,&nbsp;Vijay Kumar,&nbsp;Deepak Sharma","doi":"10.1007/s12017-022-08724-z","DOIUrl":"https://doi.org/10.1007/s12017-022-08724-z","url":null,"abstract":"<p><p>Quercetin is a polyphenolic bioactive compound highly enriched in dietary fruits, vegetables, nuts, and berries. Quercetin and its derivatives like rutin and hyperoside are known for their beneficial effects in various neurological conditions including epilepsy. The clinical studies of quercetin and its derivatives in relation to epilepsy are limited. This review provides the evidence of most recent knowledge of anticonvulsant properties of quercetin and its derivatives on preclinical studies. Additionally, the studies demonstrating antiseizure potential of various plants extracts enriched with quercetin and its derivatives has been included in this review. Herein, we have also discussed neuroprotective effect of these bioactive compound and presented underlying mechanisms responsible for anticonvulsant properties in brief. Finally, limitations of quercetin and its derivatives as antiseizure compounds as well as possible strategies to enhance efficacy have also been discussed.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"25 2","pages":"163-178"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677199","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}

{"title":"CD33/TREM2 Signaling Mediates Sleep Deprivation-Induced Memory Impairment by Regulating Microglial Phagocytosis.","authors":"Shuwen Tan,&nbsp;Hui Gao,&nbsp;Jianyu Sun,&nbsp;Na Li,&nbsp;Yuxin Zhang,&nbsp;Liu Yang,&nbsp;Min Wang,&nbsp;Qiang Wang,&nbsp;Qian Zhai","doi":"10.1007/s12017-023-08733-6","DOIUrl":"https://doi.org/10.1007/s12017-023-08733-6","url":null,"abstract":"<p><p>Sleep deprivation causes significant memory impairment in healthy adults. Extensive research has focused on identifying the biological mechanisms underlying memory impairment. Microglia-mediated synaptic elimination plays an indispensable role in sleep deprivation. Here, the potential role of the CD33/TREM2 signaling pathway in modulating memory decline during chronic sleep restriction (CSR) was evaluated. In this study, adult male C57BL/6 mice were sleep-restricted using an automated sleep deprivation apparatus for 20 h per day for 7 days. The Y-maze test revealed that spontaneous alternation was significantly reduced in CSR mice compared with control mice. The percentage of exploratory preference for the novel object in CSR mice was significantly decreased compared with that in control mice. These memory deficits correlated with aberrant microglial activation and increased phagocytic ability. Moreover, in CSR mice, the CD33 protein level in hippocampal tissue was significantly downregulated, but the TREM2 protein level was increased. In BV2 microglial cells, downregulation of CD33 increased TREM2 expression and improved microglial phagocytosis. Then, the sialic ligand monosialo-ganglioside 1 (GM1, 20 mg/kg, i.p.) was administered to mice once a day during CSR. Our results further showed that GM1 activated CD33 and consequently disturbed TREM2-mediated microglial phagocytosis. Finally, GM1 reversed CSR-induced synaptic loss and memory impairment via the CD33/TREM2 signaling pathway in the CA1 region of the hippocampus. This study provides novel evidence that activating CD33 and/or inhibiting TREM2 activity represent potential therapies for sleep loss-induced memory deficits through the modulation of microglial phagocytosis.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"25 2","pages":"255-271"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10035896","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}

{"title":"α-Synuclein Induced the Occurrence of RBD via Interaction with OX1R and Modulated Its Degradation.","authors":"Jing Kai Fan,&nbsp;Meng Chen Wang,&nbsp;Hui Min Yang,&nbsp;Jian Nan Zhang,&nbsp;Li Gu,&nbsp;Hong Zhang","doi":"10.1007/s12017-023-08735-4","DOIUrl":"https://doi.org/10.1007/s12017-023-08735-4","url":null,"abstract":"<p><p>Rapid eye movement (REM) sleep behavior disorder (RBD) is a powerful early sign of Parkinson's disease (PD), but the pathogenetic mechanism involved in RBD remains largely unexplored. α-Synuclein has been verified to form Lewy bodies in the orexin neurons, whose activity and function rely on the orexin 1 receptor (OX1R). Dysfunction of the OX1R may induce the occurrence of RBD. Here, we determined the role of the interaction between α-Synuclein and OX1R in the pathogenesis of RBD, in vitro and in vivo. We found that injection of α-Synuclein into the lateral hypothalamus area (LHA) damaged orexin neurons and induced the RBD-like sleep pattern, to further damage dopaminergic neurons and result in locomotor dysfunction in mice. α-Synuclein interacted with OX1R, promoting the degradation of OX1R through proteasomal and lysosomal pathways. In addition, overexpression of α-Synuclein downregulated OX1R-mediated signaling, subsequently leading to orexin neuron damage. We conclude that α-Synuclein induced the occurrence of RBD via interaction with OX1R and modulated its degradation. These findings provide evidence for a novel mechanism by which the association of α-Synuclein with OX1R was attributed to α-Synuclein-induced orexin neuron damage, which may be a new molecular target for an effective therapeutic strategy for RBD pathology.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"25 2","pages":"286-300"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10053504","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}

{"title":"Neuroprotective Effects of Carbonic Anhydrase Inhibition and Cyclic Adenosine Monophosphate Activation in Mouse Model of Transient Global Cerebral Ischemia and Reperfusion.","authors":"Manish Kumar,&nbsp;Komalpreet Kaur,&nbsp;Thakur Gurjeet Singh","doi":"10.1007/s12017-022-08728-9","DOIUrl":"https://doi.org/10.1007/s12017-022-08728-9","url":null,"abstract":"<p><p>Cerebral ischemia is the primary basis of stroke, both sharing common pathogenic origins leading to irreversible brain damage if blood supply is not restored promptly. Existing evidence indicates that carbonic anhydrase (CA) inhibitors (CAIs) may impart therapeutic benefits against ischemia-reperfusion (I/R) pathology via the adenylyl cyclase-cyclic adenosine monophosphate (cAMP) pathway. We hypothesize that CAI and cAMP activation may enhance the therapeutic outcome against I/R conditions. In this investigation, the potential of dichlorphenamide (CAI) and the role of cAMP against ischemia-reperfusion injury were evaluated using a transient global cerebral I/R (tGCI/R) model. Swiss albino mice were subjected to bilateral common carotid artery occlusion (BCCAo) for 20 min and reperfusion (R) or sham surgery on day 1. Dichlorphenamide (DCPA, 20 mg/kg) and/or forskolin (cAMP agonist, 3 mg/kg) was administered intraperitoneally (i.p.) after BCCAo/R for 14 days. Results showed that tGCI/R impaired neurocognitive functions and lowered brain levels of cAMP and protein kinase A (PKA) that were ameliorated by DCPA and/or forskolin (FSK). DCPA and/or FSK attenuated tGCI/R-induced brain edema, blood-brain barrier dysfunction, oxidative-nitrosative stress, pro-inflammatory cytokines, acetylcholinesterase activity, cell death, and neurotransmitter imbalance (e.g., glutamate, γ-aminobutyric acid). The study showed that DCPA improved neurological and biochemical parameters against tGCI/R injury via cAMP-PKA-mediated activation of protective mechanisms. However, DCPA and FSK in combination showed much enhanced therapeutic outcomes against tGCI/R. Therefore, CA and cAMP present novel targets that may retard the progress of a transient ischemic attack to a full-blown stroke.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"25 2","pages":"217-229"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9678625","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}

{"title":"The Promising Epigenetic Regulators for Refractory Epilepsy: An Adventurous Road Ahead.","authors":"Vemparthan Suvekbala,&nbsp;Haribaskar Ramachandran,&nbsp;Alaguraj Veluchamy,&nbsp;Mariano A Bruno Mascarenhas,&nbsp;Tharmarajan Ramprasath,&nbsp;M K C Nair,&nbsp;Venkata Naga Srikanth Garikipati,&nbsp;Rohit Gundamaraju,&nbsp;Ramasamy Subbiah","doi":"10.1007/s12017-022-08723-0","DOIUrl":"https://doi.org/10.1007/s12017-022-08723-0","url":null,"abstract":"<p><p>The attribution of seizure freedom is yet to be achieved for patients suffering from refractory epilepsy, e.g. Dravet Syndrome (DS). The confined ability of mono-chemical entity-based antiseizure drugs (ASDs) to act directly at genomic level is one of the factors, combined with undetermined seizure triggers lead to recurrent seizure (RS) in DS, abominably affecting the sub-genomic architecture of neural cells. Thus, the RS and ASD appear to be responsible for the spectrum of exorbitant clinical pathology. The RS distresses the 5-HT-serotonin pathway, hypomethylates genes of CNS, and modulates the microRNA (miRNA)/long non-coding RNA (lncRNA), eventually leading to frozen molecular alterations. These changes shall be reverted by compatible epigenetic regulators (EGR) like, miRNA and lncRNA from Breast milk (BML) and Bacopa monnieri (BMI). The absence of studious seizure in SCN1A mutation-positive babies for the first 6 months raises the possibility that the consequences of mutation in SCN1A are subsidized by EGRs from BML. EGR-dependent-modifier gene effect is likely imposed by the other members of the SCN family. Therefore, we advocate that miRNA/lncRNA from BML and bacosides/miRNA from BMI buffer the effect of SCN1A mutation by sustainably maintaining modifier gene effect in the aberrant neurons. The presence of miRNA-155-5p, -30b-5p, and -30c-5p family in BML and miR857, miR168, miR156, and miR158 in BMI target at regulating SCN family and CLCN5 as visualized by Cystoscope. Thus, we envisage that the possible effects of EGR might include (a) upregulating the haploinsufficient SCN1A strand, (b) down-regulating seizure-elevated miRNA, (c) suppressing the seizure-induced methyltransferases, and (d) enhancing the GluN2A subunit of NMDA receptor to improve cognition. The potential of these EGRs from BML and BML is to further experimentally strengthen, long-haul step forward in molecular therapeutics.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"25 2","pages":"145-162"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9733037","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}

{"title":"Induction of ICAM1 in Brain Vessels is Implicated in an Early AD Pathogenesis by Modulating Neprilysin.","authors":"Degeree Otgongerel,&nbsp;Hyeon-Ju Lee,&nbsp;Sangmee Ahn Jo","doi":"10.1007/s12017-022-08726-x","DOIUrl":"https://doi.org/10.1007/s12017-022-08726-x","url":null,"abstract":"<p><p>Intercellular adhesion molecule 1 (ICAM1) is a vessel adhesion protein induced during brain vascular inflammation, which could be closely linked with the development of Alzheimer's disease (AD). This study investigated the effect of ICAM1 on amyloid-degrading enzymes (ADEs) in endothelial cells and their potential involvement in inflammation and AD progression. TNF-α treatment increased ICAM1 in human brain microvascular endothelial cells (HBMVECs) but decreased the neprilysin (NEP) protein level. Knock-down of ICAM1 using siRNA enhanced NEP, which increased the degradation of amyloid-β. In the brains of 4-month-old AD transgenic mice (APPswe/PSEN1dE9), there were significantly higher levels of ICAM1 expression and amyloid deposits but lower levels of NEP and insulin-degrading enzymes (IDE), demonstrating an inverse correlation of ICAM1 with NEP and IDE expression. Further studies demonstrated significantly increased GFAP protein levels in the brain, specifically localized near blood vessels, of both TNF-α-injected and 4-month-old AD transgenic mice. Taken together, the induction of ICAM1 in endothelial cells suppresses NEP expression, accelerating the accumulation of amyloid-β in blood vessels. It also enhances leukocyte adhesion to blood vessels stimulating the migration of leukocytes into the brain, subsequently triggering brain inflammation.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"25 2","pages":"193-204"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677200","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}

{"title":"The Role of PGK1 in Promoting Ischemia/Reperfusion Injury-Induced Microglial M1 Polarization and Inflammation by Regulating Glycolysis.","authors":"Wei Cao,&nbsp;Zhengzhe Feng,&nbsp;Deyuan Zhu,&nbsp;Suya Li,&nbsp;Meng Du,&nbsp;Shifei Ye,&nbsp;Dayong Qi,&nbsp;Peng Li,&nbsp;Yan Chen,&nbsp;Yibin Fang","doi":"10.1007/s12017-023-08736-3","DOIUrl":"https://doi.org/10.1007/s12017-023-08736-3","url":null,"abstract":"<p><p>Stroke is a leading cause of death, with a continuously increasing incidence. As a metabolic process that catabolizes glucose pyruvate and provides adenosine triphosphate (ATP), glycolysis plays a crucial role in different diseases. Phosphoglycerate kinase 1 (PGK1) facilitates energy production with biosynthesis in many diseases, including stroke. However, the exact role of PGK1/glycolysis in stroke remains to be elucidated. A rat model of middle cerebral artery occlusion (MCAO) was used to mimic ischemia/reperfusion injuries. Oxygen glucose deprivation/re-oxygenation (OGD/R) was used to induce injury to highly aggressively proliferating immortalized (HAPI) rat microglial cells. The extracellular acidification rate (ECAR) was determined using an XFe24 Extracellular Flux Analyzer. ATP, lactate dehydrogenase, tumor necrosis factor-alpha, and interleukin-6 levels were measured using commercial kits. Chromatin immunoprecipitation assay was performed to examine the interaction between H3K27ac or p300 and the PGK1 promoter region. PGK1 was either knocked down or overexpressed by lentivirus. Thus, to examine its role in stroke, real-time polymerase chain reaction and immunoblotting were used to measure gene expression. The expression of PGK1 was increased and associated with M1 polarization and glycolysis in MCAO rat models. OGD/R promoted M1 polarization and HAPI microglial cell inflammation by regulating glycolysis. Silencing PGK1 reduced OGD/R-increased M1 polarization, inflammation, and glycolysis. Conversely, the overexpression of PGK1 promoted HAPI microglial cell inflammation by regulating glycolysis. The mechanism showed that histone acetyltransferase p300 promoted PGK1 expression through H3K27 acetylation. Finally, data indicated that silencing PGK1 inhibited microglia M1 polarization, inflammation, and glycolysis in MCAO rat models. PGK1 could promote ischemia/reperfusion injury-induced microglial M1 polarization and inflammation by regulating glycolysis, which might provide a novel direction in developing new therapeutic medications for preventing or treating stroke.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"25 2","pages":"301-311"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9671287","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}

{"title":"Protective Effect of Ergothioneine Against Stroke in Rodent Models.","authors":"Wei-Yi Ong,&nbsp;Mei-Han Kao,&nbsp;Wai-Mui Cheung,&nbsp;Damien Meng-Kiat Leow,&nbsp;Irwin Kee-Mun Cheah,&nbsp;Teng-Nan Lin","doi":"10.1007/s12017-022-08727-w","DOIUrl":"https://doi.org/10.1007/s12017-022-08727-w","url":null,"abstract":"<p><p>Ergothioneine (ET) is a naturally occurring antioxidant and cytoprotective agent that is synthesized by fungi and certain bacteria. Recent studies have shown a beneficial effect of ET on neurological functions, including cognition and animal models of depression. The aim of this study is to elucidate a possible effect of ET in rodent models of stroke. Post-ischemic intracerebroventricular (i.c.v.) infusion of ET significantly reduced brain infarct volume by as early as 1 day after infusion in rats, as shown by triphenyltetrazolium chloride (TTC) assay. There was a dose-dependent increase in protection, from 50 to 200 ng of ET infusion. These results suggest that ET could have a protective effect on CNS neurons. We next elucidated the effect of systemic ET on brain infarct volume in mice after stroke. Daily i.p. injection of 35 mg/kg ET (the first dose being administered 3 h after stroke) had no significant effect on infarct volume. However, daily i.p. injections of 70 mg/kg, 100 mg/kg, 125 mg/kg and 150 mg/kg ET, with the first dose administered 3 h after stroke, significantly decreased infarct volume at 7 days after vessel occlusion in mice. In order to elucidate at what time interval during the 7 days there could be effective protection, a second set of experiments was carried out in mice, using one of the effective loading protocols, i.e. 125 mg/kg i.p. ET but the brains were analyzed at 1, 4 and 7 days post-stroke by MRI. We found that ET was already protective against neuronal injury and decreased the size of the brain infarct from as early as 1 day post-stroke. Behavioral experiments carried out on a third set of mice (using 125 mg/kg i.p. ET) showed that this was accompanied by significant improvements in certain behaviors (pole test) at 1 day after stroke. Together, results of this study indicate that i.c.v. and systemic ET are effective in reducing brain infarct volume after stroke in rodent models.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"25 2","pages":"205-216"},"PeriodicalIF":3.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9677659","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}