Experimental Neurology最新文献

{"title":"Nucleophosmin 1 overexpression enhances neuroprotection by attenuating cellular stress in traumatic brain injury","authors":"Jiashuo Zhao ,&nbsp;Weixin Xing ,&nbsp;Chengyuan Ji ,&nbsp;Hongwei Hu ,&nbsp;Yuanqing Zhang ,&nbsp;Zongqi Wang ,&nbsp;Jiangang Liu","doi":"10.1016/j.expneurol.2024.115019","DOIUrl":"10.1016/j.expneurol.2024.115019","url":null,"abstract":"<div><h3>Background</h3><div>Traumatic Brain Injury (TBI) is a multifaceted injury that can cause a wide range of symptoms and impairments, leading to significant effects on brain function. Nucleophosmin 1 (NPM1), a versatile phosphoprotein located in the nucleolus, is being recognized as a possible controller of cellular stress reactions and could be important in reducing neuro dysfunction caused by TBI. However the critical roles of NPM1 in cellular stress in TBI remains unclear.</div></div><div><h3>Methods</h3><div>We employed a control cortical impact mouse model and a scratch-induced primary neuronal culture model. Hematoxylin and eosin staining was used to evaluate tissue damage and cellular changes, with NPM1 expression in the cortical area assessed through immunofluorescence staining and Western blot analysis. Neuronal morphology was assessed using Nissl staining. Behavioral assessments were performed to evaluate the impact of NPM1 overexpression on neurobehavioral results in TBI mice. Mitochondrial function was assessed using an Extracellular Flux Analyzer.</div></div><div><h3>Results</h3><div>Following TBI, an increase in NPM1 expression was observed, with a peak at 72 h post-injury. Increased levels of NPM1 resulted in decreased neuronal cell death, as shown by Nissl staining, and lower levels of Caspase 8, APE1, H2AX, and 8-OHDG expression, indicating a reduction in DNA damage. NPM1 overexpression also resulted in improved neurobehavioral outcomes, characterized by decreased neurological deficits and enhanced motor function post-TBI. Additionally, <em>in vitro</em>, scratch-induction experiments revealed that NPM1 overexpression mitigated mitochondrial damage, as evidenced by the downregulation of P53, BCL2, and Cyto C expression levels and improvements in mitochondrial respiratory function.</div></div><div><h3>Conclusion</h3><div>These findings suggest NPM1 as a promising target for developing interventions to alleviate TBI-related cellular stress and promote neuronal survival.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-dependent arachidonic acid metabolism and functional changes in rats bladder tissue after suprasacral spinal cord injury","authors":"Yi Rong ,&nbsp;Yinbo Kang ,&nbsp;Jie Wen ,&nbsp;Qian Gong ,&nbsp;Wenlong Zhang ,&nbsp;Ke Sun ,&nbsp;Weibing Shuang","doi":"10.1016/j.expneurol.2024.114989","DOIUrl":"10.1016/j.expneurol.2024.114989","url":null,"abstract":"<div><h3>Background</h3><div>A critical aspect affecting the quality of life in Traumatic spinal cord injury (TSCI) patients is bladder dysfunction. Metabolities in arachidonic acid are crucial lipid signaling molecules involved innumerous physiological processes. In this study, We are the first use eicosanoid metabolomics detrusor contraction examine, to assess the effect of the arachidonic acid metabolic in bladder dysfunction following TSCI. In additon, we explore the time of inflammatory and function changes in bladder tissue.</div></div><div><h3>Methods</h3><div>Adult male Sprague-Dawley rats were subjected to improved Weight Drop method surgeries. Detrusor contraction examination, urodynamic examination, eicosanoid metabolomics, transmission electron microscopy, Elisa and histological staining were performed to assess the change of inflammatory, metabolic and function variation over time after TSCI.</div></div><div><h3>Results</h3><div>Following TSCI, before the variations of bladder function, inflammatory changes including the increase of inflammatory factors, mitochondrial damage, and slight lipid peroxidation, occurred in bladder tissue. And the inflammatory changes gradually decreases over time. However, From the third day after TSCI, secondary lesions appeared in bladder tissue. Not only did inflammation-related indexes increase again, the degree of mitochondrial damage and lipid peroxidation increased, but also the contractility of detrusor began to change significantly. We also found that the content of metabolites in arachidonic acid metabolic pathway and the degree of detrusor contractility change showed a strong correlation. In addition, we found that rats had moved beyond the spinal shock stage on the seventh day after TSCI.</div></div><div><h3>Conclusion</h3><div>Altogether, we are the first to demonstrate that abnormal arachidonic acid metabolism plays an important role in bladder dysfunction after TSCI. We also demonstrate that 3d is a critical juncture for changes in rat bladder tissue, which indicates it is an important juncture in the treatment of neurogenic bladder.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GlyT1 inhibition promotes neuroprotection in the middle cerebral artery occlusion model through the activation of GluN2A-containing NMDAR","authors":"Daniel Pereira Cavalcante ,&nbsp;Antonio Ítalo dos Santos Nunes ,&nbsp;Eduardo Rosa da Silva ,&nbsp;Gustavo Almeida de Carvalho ,&nbsp;Raphaela Almeida Chiareli ,&nbsp;Onésia Cristina Oliveira-Lima ,&nbsp;Giovanni Ortiz-Leoncini ,&nbsp;Henning Ulrich ,&nbsp;Renato Santiago Gomez ,&nbsp;Mauro Cunha Xavier Pinto","doi":"10.1016/j.expneurol.2024.115006","DOIUrl":"10.1016/j.expneurol.2024.115006","url":null,"abstract":"<div><div>Glycine Transporter Type 1 (GlyT1) inhibition confers neuroprotection against different forms of cerebral damage. This effect occurs through the elevation of synaptic glycine concentrations, which enhances <em>N</em>-methyl-<span>d</span>-aspartate receptor (NMDAR) activation by glutamate. To investigate the neuroprotective mechanism of GlyT1 inhibition, we used the Middle Cerebral Artery Occlusion (MCAO) model in male C57BL/6 mice, aged 10–12 weeks. We administered N-[3-(4′-fluorophenyl)-3-(4′-phenylphenoxy)propyl] sarcosine (NFPS), a GlyT1 inhibitor, 24 h prior to ischemia induction. NFPS pretreatment provided significant neuroprotection in the MCAO model, associated with modulation of pathways related to long-term potentiation. Specifically, GluN2A subunit expression was upregulated, while GluN2B subunit expression was downregulated in cortical areas, correlating with enhanced phosphorylation of CaMKIV and CREB proteins. Coadministration with the GluN2B antagonist Eliprodil or the CREB inhibitor C646 did not affect the neuroprotective effects of NFPS pretreatment, but TCN-201, a specific GluN2A antagonist, disrupted these effects. These findings suggest that GlyT1 inhibition mediates neuroprotection through activation of GluN2A-containing NMDARs and the GluN2A/CaMKIV/CREB signaling cascade, thereby modulating the balance between GluN2A and GluN2B subunits.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress in the regulatory mechanism of mitophagy in chronic cerebral ischemic neuronal injury","authors":"Lihong Li ,&nbsp;Rui Yuan ,&nbsp;Moxin Wu ,&nbsp;Xiaoping Yin ,&nbsp;Manqing Zhang ,&nbsp;Zhiying Chen","doi":"10.1016/j.expneurol.2024.115003","DOIUrl":"10.1016/j.expneurol.2024.115003","url":null,"abstract":"<div><div>Chronic cerebral ischemia (CCI) is a common clinical syndrome that can impact various cerebrovascular diseases. Its pathological mechanism of injury involves energy imbalance, oxidative stress, inflammatory response, and many other processes. Neuronal damage occurs in a complex and multifaceted manner. This article provides a detailed discussion of the activation and inhibition mechanisms of mitophagy under cerebral ischemia and considers the advantages and disadvantages of mitophagy in the recovery process of ischemic brain injury. Finally, we address the future direction of research on neuronal injury and the regulatory mechanisms of mitophagy in chronic cerebral ischemia. Future studies should focus on drug intervention at specific regulatory points and the cross-regulation of related signaling pathways to comprehensively deepen understanding of the mechanisms of neuronal injury in chronic cerebral ischemia. Promising interventions could potentially improve the treatment and outcomes of chronic cerebral ischemia.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early intervention using long-term rhythmic pulsed magnetic stimulation alleviates cognitive decline in a 5xFAD mouse model of Alzheimer's disease","authors":"Xue Wang ,&nbsp;Qingmeng Wang ,&nbsp;Xuting Wang ,&nbsp;Haoyu Zhao ,&nbsp;Chuncheng Zhao ,&nbsp;Yangkun Jiao ,&nbsp;Hongkai Shi ,&nbsp;Changyou Chen ,&nbsp;Haitao Chen ,&nbsp;Pingping Wang ,&nbsp;Tao Song","doi":"10.1016/j.expneurol.2024.115002","DOIUrl":"10.1016/j.expneurol.2024.115002","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer's disease (AD) is the most prevalent form of dementia, but no effective therapeutic strategy is available to date. Rhythmic magnetic stimulation is an attractive means of neuron modulation that could be beneficial for restoring learning and memory abilities.</div></div><div><h3>Objective</h3><div>To assess the effect of a compound pulsed rhythmic magnetic field (cPMF) on cognition during AD progression and to explore the appropriate cPMF intervention period.</div></div><div><h3>Methods</h3><div>Female 5xFAD mice aged 10 weeks and 18 weeks were exposed to cPMF with a carrier frequency of 40 Hz, repeated at 5 Hz for 1 h/d for 8 consecutive weeks. The Morris water maze (MWM) test was used for cognitive behavioral assessment. Furthermore, changes in molecular pathology within the brain were detected using immunofluorescence staining and real-time PCR.</div></div><div><h3>Results</h3><div>10-week-old AD mice treated with cPMF explored the target quadrant more frequently than sham-exposed AD mice in MWM test, exhibiting improved learning and memory abilities. Additionally, cPMF exposure alleviated Aβ plaque deposition and astrogliosis in the AD brain. Moreover, neurotrophic factor fibroblast growth factor 1 (FGF1) in the AD brain was upregulated by cPMF treatment. However, in 18-week-old AD mice treated with cPMF, cognitive performance and <em>Fgf1</em> gene expression were not significantly improved, although Aβ plaque deposition and astrogliosis were alleviated.</div></div><div><h3>Conclusion</h3><div>Early intervention via long-term rhythmic cPMF stimulation may alleviate the histopathological features and enhance neuroprotective gene <em>Fgf1</em> expression, thereby improving the cognitive performance of 5xFAD mice, which should provide promising insight for the clinical treatment of patients with AD.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DDAH1 deficiency exacerbates cerebral vascular endothelial dysfunction by aggravating BBB disruption and oxidative stress in thoracic blast-induced brain injury","authors":"Peifang Cong,&nbsp;Changci Tong,&nbsp;Shun Mao,&nbsp;Lin Shi,&nbsp;Mingxiao Hou,&nbsp;Yunen Liu","doi":"10.1016/j.expneurol.2024.114994","DOIUrl":"10.1016/j.expneurol.2024.114994","url":null,"abstract":"<div><div>As terrorist incidents and underground explosion events have become more frequent around the world, brain injury caused by thoracic blast exposure has been more highlighted due to its injured organ, subsequent social and economic burden. It has been reported dimethylarginine dimethylaminohydrolase 1 (DDAH1) plays important roles in regulating vascular endothelial injury repair and angiogenesis, but its role in thoracic blast-induced brain injury remains to be explained. This study seeks to investigate the mechanism of DDAH1 on thoracic blast-induced brain injury. 40 C57BL/6 wild type mice and 40 DDAH1 knockout mice were randomly and equally divided into control group and blast group, respectively. The integrity of blood-brain barrier (BBB) was detected by Evans blue test. The serum inflammatory factors, nitric oxide (NO) contents, and asymmetric dimethylarginine (ADMA) levels were determined through ELISA. HE staining and reactive oxygen species (ROS) detection were performed for histopathological changes. Western blot was used to detect the proteins related to oxidative stress, tight junction, focal adhesion, vascular endothelial injury, and the DDAH1/ADMA/eNOS signaling pathway. DDAH1 deficiency aggravated thoracic blast-induced BBB leakage, inflammatory response, and the increased levels of inflammatory-related factors. Additionally, DDAH1 deficiency also increased ROS generation, MDA and IRE-α expression. Regarding cerebral vascular endothelial dysfunction, DDAH1 deficiency increased the expression of MCAM, FN1, LIMK1, VEGF, MMP9, Vimentin and N-cadherin, while lowering the expression of FMR1, Occludin, claudin-3, claudin-5, Lyn, LIMA1, Glrb, Sez6, Dystrophin, and phosphorylation of VASP. Also, DDAH1 deficiency exacerbated explosion-induced increase of ADMA and decrease of eNOS activity and NO contents. Thus, we conclude that DDAH1 could prevent cerebral vascular endothelial dysfunction and related injury by inhibiting ADMA signaling and increasing eNOS activity in thoracic blast induced brain injury.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential role of solid lipid curcumin particle (SLCP) as estrogen replacement therapy in mitigating TDP-43-related neuropathy in the mouse model of ALS disease","authors":"Pritha Majumder ,&nbsp;Tsung-I Hsu ,&nbsp;Chaur-Joug Hu ,&nbsp;Jeffrey K. Huang ,&nbsp;Yi-Chao Lee ,&nbsp;Yi-Chen Hsieh ,&nbsp;Asmar Ahsan ,&nbsp;Chi-Chen Huang","doi":"10.1016/j.expneurol.2024.114999","DOIUrl":"10.1016/j.expneurol.2024.114999","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Amyotrophic lateral sclerosis (ALS) was first identified in 1869, but it wasn't until the 2014 Ice Bucket Challenge that widespread attention was drawn to the disease. Since then, substantial research has been dedicated to developing treatments for ALS. Despite this, only three drugs - riluzole, edaravone and AMX0035, have been approved for clinical use, and they can only temporarily alleviate mild symptoms without significant disease modification or cure. Therefore, there remains a critical unmet need to identify disease modifying or curative therapies for ALS. The higher incidence and more severe progression of ALS and FTLD (frontotemporal lobar degeneration) observed in men and postmenopausal woman compared to young women suggests that sex hormones may significantly influence disease onset and progression. In both animal models and human clinical studies, 17β estradiol (E2) has been shown to delay and improve the outcomes of many neurodegenerative diseases. Here, we examined the role of TDP-43 in the regulation of estrogen-related enzymes, CYP19A1 and CYP3A4. In addition, we examined the impact of curcumin on the regulation of estrogen E2 levels and TDP-43-associated neuropathy as a potential therapeutic strategy for the treatment of FTLD and ALS.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Prp-TDP-43&lt;sup&gt;A315T&lt;/sup&gt; mice was used as a model of ALS/FTLD to examine the expression patterns of E2 and its biosynthesis and degradation enzymes, CYP19A1 and CYP3A4. Moreover, the molecular mechanisms and the potency of solid lipid curcumin particles (SLCP) as an E2 replacement therapy for TDP-43 associated neuropathy was analyzed. We further examined the survival rates and the pathological TDP43 patterns in female and male Prp-TDP-43&lt;sup&gt;A315T&lt;/sup&gt; mice administrated with or without SLCP. In addition, the changed expression levels of enzymes corresponding to E2 biosynthesis and degradation in the spinal cord of female and male Prp-TDP-43&lt;sup&gt;A315T&lt;/sup&gt; mice with or without SLCP were determined.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We found that in addition to E2, the expression patterns of CYP19A1 and CYP3A4 proteins differed between Prp-TDP-43&lt;sup&gt;A315T&lt;/sup&gt; mice compared to wild-type control, suggesting that toxic phosphorylated TDP43 oligomers may disrupt the balance between CYP19A1 and CYP3A4 expression, leading to reduced estrogen biosynthesis and accelerated degradation. In addition, we found that oral administration of SLCP prolonged the survival rates in female Prp-TDP-43&lt;sup&gt;A315T&lt;/sup&gt; mice and significantly reduced the pathological insoluble phosphorylated TDP-43 species. Furthermore, SLCP attenuated disease progression associated with TDP-43-related neuropathies through modulating estrogen biosynthesis and the activity of CYP450 enzymes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Our results showed that Prp-TDP-43&lt;sup&gt;A315T&lt;/sup&gt; mice exhibit altered estradiol levels. Moreover, we demonstrated the efficacy of SLCP as","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventive effects of transcranial photobiomodulation on epileptogenesis in a kainic acid-induced rat epilepsy model","authors":"Jing You ,&nbsp;Jannon Fuchs ,&nbsp;Miaomiao Wang ,&nbsp;Qichan Hu ,&nbsp;Xiaoxiao Tao ,&nbsp;Elizabeth Krolczyk ,&nbsp;Tanya Tirumala ,&nbsp;Anatol Bragin ,&nbsp;Hanli Liu ,&nbsp;Jerome Engel Jr ,&nbsp;Lin Li","doi":"10.1016/j.expneurol.2024.115005","DOIUrl":"10.1016/j.expneurol.2024.115005","url":null,"abstract":"<div><h3>Objective</h3><div>Temporal lobe epilepsy affects nearly 50 million people worldwide and is a major burden to families and society. A significant portion of patients are living in developing countries with limited access to therapeutic resources. This highlights the urgent need to develop more readily available, noninvasive treatments for seizure control. This research explored the effectiveness of transcranial photobiomodulation (tPBM), a non-invasive method utilizing photon-tissue interactions, for preventing epileptogenesis and controlling seizures.</div></div><div><h3>Methods</h3><div>In a kainic acid (KA)-induced rat model of epilepsy, two different wavelengths of tPBM, 808 nm and 940 nm, were applied separately in two groups of animals (KA+808 and KA+940). The ability of tPBM for seizure control was evaluated by comparing the occurrence rate of interictal epileptiform discharges (IED) and behavioral seizures among three groups: KA, KA+808, KA+940. Prevention of epileptogenesis was assessed by comparing the occurrence rate of high frequency oscillations (HFOs), especially fast ripple (FR) rate, among the three groups. Nissl staining and immunostaining for the apoptosis marker caspase-3 were used as indications of neuroprotection.</div></div><div><h3>Results</h3><div>The KA+808 group and the KA+940 group showed significantly lower FR and IED rates compared to the KA group. Weekly FR rates started to drop during the first week of tPBM treatment. The KA+808 and KA+940 groups also displayed milder seizure behaviors and less neuronal loss in hippocampal areas compared to KA rats without tPBM treatment. Similarly, lower caspase-3 levels in the KA+808 and KA+940 compared with the KA group suggested effectiveness of tPBM in reducing cell death.</div></div><div><h3>Significance</h3><div>tPBM of 808 nm/940 nm showed effectiveness in suppressing epileptogenesis and ictogenesis in the KA-induced rat epilepsy model. This effectiveness of tPBM can be linked to the neuroprotection benefits of photon-tissue interactions. Further studies are warranted to elucidate the fundamental mechanism of tPBM protection, determine optimal treatment parameters and validate its effectiveness in other epilepsy models.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactiplantibacillus plantarum SG5 inhibits neuroinflammation in MPTP-induced PD mice through GLP-1/PGC-1α pathway","authors":"Yueyan Qi ,&nbsp;Yuxuan Dong ,&nbsp;Jinhu Chen ,&nbsp;Siyou Xie ,&nbsp;Xin Ma ,&nbsp;Xueping Yu ,&nbsp;Yang Yu ,&nbsp;Yanqin Wang","doi":"10.1016/j.expneurol.2024.115001","DOIUrl":"10.1016/j.expneurol.2024.115001","url":null,"abstract":"<div><div>Mounting evidence suggests that alterations in gut microbial composition play an active role in the pathogenesis of Parkinson's disease (PD). Probiotics are believed to modulate gut microbiota, potentially influencing PD development through the microbiota-gut-brain axis. However, the potential beneficial effects of <em>Lactiplantibacillus plantarum</em> SG5 (formerly known as <em>Lactobacillus plantarum</em>, abbreviated as <em>L. plantarum</em>) on PD and its underlying mechanisms remain unclear. In this study, we employed immunofluorescence, Western blotting, ELISA, and 16S rRNA gene sequencing to investigate the neuroprotective effects of <em>L. plantarum</em> SG5 against neuroinflammation in an MPTP-induced PD model and to explore the underlying mechanisms. Our results demonstrated that <em>L. plantarum</em> SG5 ameliorated MPTP-induced motor deficits, dopaminergic neuron loss, and elevated α-synuclein protein levels. Furthermore, SG5 inhibited MPTP-triggered overactivation of microglia and astrocytes in the substantia nigra (SN), attenuated disruption of both blood-brain and intestinal barriers, and suppressed the release of inflammatory factors in the colon and SN. Notably, SG5 modulated the composition and structure of the gut microbiota in mice. The MPTP-induced decrease in colonic GLP-1 secretion was reversed by SG5 treatment, accompanied by increased expression of GLP-1R and PGC-1α in the SN. Importantly, the GLP-1R antagonist Exendin 9–39 and PGC-1α inhibitor SR18292 attenuated the protective effects of SG5 in PD mice. In conclusion, we demonstrate a neuroprotective role of <em>L. plantarum</em> SG5 in the MPTP-induced PD mouse model, which likely involves modulation of the gut microbiota and, significantly, the GLP-1/PGC-1α signaling pathway.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL5-mediated 18S rRNA m6A modification promotes corticospinal tract sprouting after unilateral traumatic brain injury","authors":"Zhenpeng Li ,&nbsp;An Jiang ,&nbsp;Jintao Fang ,&nbsp;Yifei Jiang ,&nbsp;Wenting He ,&nbsp;Liwei Yan ,&nbsp;Shuai Qiu ,&nbsp;Bengang Qin ,&nbsp;Qingtang Zhu ,&nbsp;Honggang Wang","doi":"10.1016/j.expneurol.2024.115000","DOIUrl":"10.1016/j.expneurol.2024.115000","url":null,"abstract":"<div><div>The key to improving function of an impaired limb after unilateral brain injury is promotion of corticospinal tract (CST) sprouting across the midline into the denervated hemicord. Previous studies have unveiled specific genes that regulate CST sprouting. CST sprouting may also be regulated by RNA modification. We examined METTL5, the methyltransferase for 18S rRNA m⁶A modification, as a regulator of CST sprouting in mice. Overexpression of METTL5 in contralesional corticospinal neurons promoted CST sprouting after unilateral traumatic brain injury. Mechanically, METTL5-mediated 18S rRNA m⁶A modification promoted the translation efficiency (TE) of various genes. Notably, the upregulation of TE in the gene <em>Cfl1,</em> which encodes cofilin, led to an increase in its expression. Additionally, the upregulation of TE in the gene <em>Inpp5k</em> led to the activation of cofilin. Active cofilin stimulates actin polymerization and facilitates protrusion and bundling of microtubules, thus promoting axon outgrowth. These findings offer valuable insights for developing novel strategies to promote CST sprouting.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}