Neuroimmunomodulation最新文献

{"title":"Integrated Proteomic and Phosphoproteomic Analysis of the Hippocampus in a Mouse Model of Early Life Inflammation.","authors":"Xin-Miao Wu, Yu-Zhu Gao, Ting-Ting Zhu, Han-Wen Gu, Jian-Hua Tong, Jie Sun, Jian-Jun Yang, Mu-Huo Ji","doi":"10.1159/000527975","DOIUrl":"10.1159/000527975","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammation in early life is a risk factor for the development of neuropsychiatric diseases later in adolescence and adulthood, yet the underlying mechanism remains elusive. In the present study, we performed an integrated proteomic and phosphoproteomic analysis of the hippocampus to identify potential molecular mechanisms of early life inflammation-induced cognitive impairment.</p><p><strong>Methods: </strong>Both female and male mice received a single intraperitoneal injection of 100 μg/kg lipopolysaccharide (LPS) on postnatal day 10 (P10). Behavioral tests, including open field, elevated plus-maze, and Y-maze tests, were performed on P39, P40, and P41, respectively. After behavioral tests, male mice were sacrificed. The whole brain tissues and the hippocampi were harvested on P42 for proteomic, phosphoproteomic, Western blot, and Golgi staining.</p><p><strong>Results: </strong>Early life LPS exposure induced cognitive impairment in male mice but not in female mice, as assessed by the Y-maze test. Therefore, following biochemical tests were conducted on male mice. By proteomic analysis, 13 proteins in LPS group exhibited differential expression. Among these, 9 proteins were upregulated and 4 proteins were downregulated. For phosphoproteomic analysis, a total of 518 phosphopeptides were identified, of which 316 phosphopeptides were upregulated and 202 phosphopeptides were downregulated in the LPS group compared with the control group. Furthermore, KEGG analysis indicated that early life LPS exposure affected the glutamatergic synapse and neuroactive ligand-receptor interaction, which were associated with synaptic function and energy metabolism. Increased level of brain protein i3 (Bri3), decreased levels of PSD-95 and mGLUR5, and dendritic spine loss after early life LPS exposure further confirmed the findings of proteomic and phosphoproteomic analysis.</p><p><strong>Conclusions: </strong>Our findings demonstrated that neuroinflammation and impaired synapse may be involved in early life inflammation-induced cognitive impairment. Future studies are required to confirm our preliminary results.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"28-41"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10480675","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":"Effect of Leuprolide Acetate, a GnRH Agonist, on Neuroinflammation and Anxiety-Like Behavior after Mild Hypoxic-Ischemic Encephalopathy in Rat Model.","authors":"Karina Alejandra Pedroza-García, Denisse Calderón-Vallejo, Daniel Cervantes-García, Andrés Quintanar-Stephano, Eva Salinas, J Luis Quintanar","doi":"10.1159/000533388","DOIUrl":"10.1159/000533388","url":null,"abstract":"<p><strong>Background: </strong>Mild hypoxic-ischemic encephalopathy (HIE) is a condition that predisposes to negative outcomes such as neuroanatomical injury, mood disorders, and motor or cognitive disabilities. The neuroinflammation plays an important role in the neurological damage; therefore, reducing it could provide neuroprotection. The leuprolide acetate (LA) has shown to have neuroregenerative and immunomodulator properties in other nervous system injuries.</p><p><strong>Objective: </strong>The aim of this study was to evaluate the immunomodulatory effect of LA in the acute phase of mild HIE and its effects in motor activity and behavior in a subacute phase.</p><p><strong>Method: </strong>Forty-five Wistar rats on postnatal day 7 were divided into Sham, HIE treated with saline solution (HIE-SS), and HIE-LA. The HIE was performed cutting of the right carotid artery followed by 60 min of hypoxia. The expression of the inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and the chemokine CXCL-1 were evaluated 72 h after HIE by RT-qPCR and the motor activity and behavior were evaluated by open field test at postnatal day 33.</p><p><strong>Results: </strong>HIE-SS animals showed increased expression of IL-1β, TNF-α, IFN-γ, and CXCL-1 genes in injured tissue. However, the HIE-LA group exhibited similar expression levels of IL-1β and TNF-α to the Sham group, while IFN-γ and CXCL-1 mRNA expression were attenuated with LA treatment. LA treatment also prevented anxiety-like behavior in the open field test.</p><p><strong>Conclusion: </strong>Treatment with LA partially reverses HIE-induced neuroinflammation and prevents anxiety-like behavior in neonatal rats.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"206-212"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10048200","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":"Ageing Affects Thymopoiesis and Experimental Autoimmune Encephalomyelitis Development in a Strain-Dependent Manner.","authors":"Zorica Stojić-Vukanić, Marija Petrušić, Ivan Pilipović, Gordana Leposavić","doi":"10.1159/000535150","DOIUrl":"10.1159/000535150","url":null,"abstract":"<p><strong>Introduction: </strong>Considering significance of mechanisms of central tolerance for development of autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), and suppressive influence of circulating proinflammatory cytokines and alterations in brain-thymus communication, characteristic for the central nervous system (CNS) autoimmune diseases, on thymopoiesis, the study interogated putative strain-based thymus-related specificities relevant for the opposite effects of ageing on susceptibility of Dark Agouti (DA) and Albino Oxford (AO) rats to EAE.</p><p><strong>Methods: </strong>Quantitative and qualitative changes in thymopoiesis including underlying mechanisms were examined using flow cytometry and RT-qPCR quantification of mRNAs for molecules relevant for integrity of stroma and T-cell development, respectively.</p><p><strong>Results: </strong>With ageing, differently from DA rats, in AO rats the surface density of CD90, a negative regulator of selection threshold, on thymocytes undergoing lineage commitment was upregulated (consistent with TGF-β expression downregulation), whereas the generation of natural CD4+CD25+Foxp3+ regulatory T cells (nTregs) was impaired reflecting differences in thymic expression of cytokines supporting their development. Additionally, specifically in old AO rats, in whom EAE development depends on IL-17-producing CD8+ T cells, their thymic differentiation was augmented, reflecting augmented thymic IL-4 expression. In turn, differently from old DA rats developing self-limiting EAE, in age-matched AO rats developing EAE of prolonged duration, EAE development led to impaired generation of nTregs and accumulation of proinflammatory, cytotoxic CD28-CD4+ T cells in the periphery.</p><p><strong>Discussion: </strong>The study indicates that strain differences in age-related changes in the efficacy of central tolerance, in addition to enhanced thymic generation of CD8+ T cells prone to differentiate into IL-17-producing cells, could partly explain the opposite effect of ageing on DA and AO rat susceptibility to EAE induction. Additionally, it suggested that EAE development leading to a less efficient thymic output of CD4+ cells and nTregs in old AO rats than their DA counterparts could contribute to prolonged EAE duration in AO compared with DA rats.</p><p><strong>Conclusion: </strong>The study warns to caution when designing therapeutic interventions to enhance thymic activity in genetically diverse populations, e.g., humans, and interpreting their outcomes. Furthermore, it indicates that CNS autoimmune pathology may additionally worsen thymic involution and age-related immune changes.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"346-373"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89718962","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":"15th Conference of the German Endocrine-Brain- Immune-Network (GEBIN) Ulm, Germany, September 28 - September 30, 2023.","authors":"","doi":"10.1159/000533771","DOIUrl":"https://doi.org/10.1159/000533771","url":null,"abstract":"","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"30 Suppl 2 ","pages":"1-60"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470856","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":"2nd European Psychoneuroimmunology Network (EPN) Autumn School: The skin-brain axis and the breaking of barriers.","authors":"Eva Peters","doi":"10.1159/000533613","DOIUrl":"10.1159/000533613","url":null,"abstract":"<p><p>none.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"30 Suppl 1 ","pages":"8-34"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10173652","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":"Neurotensin-Binding Immunoglobulin G in Patients with Parkinson's Disease.","authors":"Zamira M Muruzheva, Daniil S Egorov, Margarita T Absalyamova, Dmitrii S Traktirov, Marina N Karpenko, Serguei O Fetissov","doi":"10.1159/000527872","DOIUrl":"10.1159/000527872","url":null,"abstract":"<p><strong>Introduction: </strong>Neurotensin (NTS) is a 13-amino acid neuropeptide functionally linked with the brain dopaminergic system via expression of the NTS peptide or its receptor in dopamine neurons. Neuropeptide-binding immunoglobulins (Igs) are present in humans and can be involved in both physiological and pathological processes. Considering the functional link between NTS and dopamine neurons, we studied the occurrence of NTS-binding IgG autoantibodies in patients with Parkinson's disease (PD).</p><p><strong>Methods: </strong>Plasma levels of NTS-binding IgG were analyzed using enzyme-linked immunosorbent assay in both male and female PD patents and in age-matched healthy controls. Possible microbial origin of NTS cross-reactive IgG was analyzed by sequence alignment of the 6-amino acid C-terminal NTS pharmacophore with bacterial and viral proteins from the public NCBI database.</p><p><strong>Results: </strong>NTS-binding IgG were detected in the plasma of all study subjects, while their levels were consistently lower in PD patients versus controls (p = 0.0001), independently from age or sex of the study participants. Moreover, PD patients with a more severe stage (2.5-3.0) of the disease had lower levels of NTS-binding IgG (p = 0.0004) than those with a milder stage (1.0-2.0). Furthermore, PD patients taking amantadine or high doses of levodopa had higher levels of NTS-binding IgG than those without medication. Contiguous sequence homology for the NTS pharmacophore was present in several microbial proteins occurring in human gut microbiota.</p><p><strong>Discussion: </strong>The study revealed that NTS-binding IgG occur naturally in humans and that PD patients display their low plasma levels accentuated by disease severity. The functional significance of this finding and its relevance to the pathophysiology of PD, including putative link to gut microbiota, remain to be studied.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"15-27"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10695055","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":"MiR-124 Reduced Neuroinflammation after Traumatic Brain Injury by Inhibiting TRAF6.","authors":"Yongxiang Yang, Yuqin Ye, Kexia Fan, Jianing Luo, Yongjian Yang, Yuan Ma","doi":"10.1159/000528502","DOIUrl":"10.1159/000528502","url":null,"abstract":"<p><strong>Introduction: </strong>Neuroinflammation contributes to secondary injury after traumatic brain injury (TBI), which has been mainly mediated by the microglia. MiR-124 was reported to play an important role in the polarization of microglia by targeting TLR4 signaling pathway. However, the role and mechanism of miR-124 in neuroinflammation mediated by microglia after TBI is unclear. To clarify this, we performed this research.</p><p><strong>Methods: </strong>The expression of miR-124 was first measured by RT-PCR in the injured brain at 1/3/7 days post-TBI. Then, miR-124 mimics or inhibitors administration was used to interfere the expression of miR-124 at 24 h post-TBI. Subsequently, the microglia polarization markers were detected by RT-PCR, the expression of inflammatory cytokines was detected by ELISA, the expression of TLR4/MyD88/IRAK1/TRAF6/NF-κB was measured by WB, and the neurological deficit was evaluated by NSS and MWM test. At last, in vitro experiments were performed to explore the exact target molecule of miR-124 on TLR4 signaling pathway.</p><p><strong>Results: </strong>Animal research indicated that the expression of miR-124 was downregulated after TBI. Upregulation of miR-124 promoted the M2 polarization of microglia and inhibited the activity of TLR4 pathway, as well as reduced neuroinflammation and neurological deficit after TBI. In vitro experiments indicated that miR-124 promoted the M2 polarization of microglia and reduced neuroinflammation by inhibiting TRAF6.</p><p><strong>Conclusion: </strong>This study demonstrated that upregulation of miR-124 promoted the M2 polarization of microglia and reduced neuroinflammation after TBI by inhibiting TRAF6.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"30 1","pages":"55-68"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10804927","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":"Hypothalamic-Pituitary Axis Function and Adrenal Insufficiency in COVID-19 Patients.","authors":"Emre Durcan, Aysa Hacioglu, Zuleyha Karaca, Kursad Unluhizarci, Mustafa Sait Gonen, Fahrettin Kelestimur","doi":"10.1159/000534025","DOIUrl":"10.1159/000534025","url":null,"abstract":"<p><p>The outbreak of COVID-19 has affected more than half a billion people worldwide and caused more than 6 million deaths since 2019. The responsible virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affects the lungs, but it has multisystemic effects. It is well known that dysfunction of multiple endocrine organs may occur during or after COVID-19. Impairment of the hypothalamic-pituitary-adrenal (HPA) axis is of utmost importance as it may lead to death if went undiagnosed. SARS-CoV-2 may cause both primary and secondary adrenal insufficiencies (AIs). The clinical manifestations of AI are generally non-specific and might be attributed to the complications caused by the infection itself. The underlying pathogenetic mechanisms were explained by the immunogenic, vascular effects of the infection or the direct effects of the virus. The diagnosis of AI in critically ill patients with COVID-19 is not straightforward. There is lack of consensus on the cut-off values of basal serum cortisol levels and stimulation tests during the disease. Here we review the literature with a special regard on the evaluation of the HPA axis in patients with COVID-19. We conclude that the possibility of AI should always be kept in mind when dealing with patients with COVID-19, and repeated basal cortisol measurements and the ACTH stimulation test results could guide the clinician during the diagnostic process.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":" ","pages":"215-225"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10222297","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":"Retraction Statement","authors":"","doi":"10.1159/000531807","DOIUrl":"https://doi.org/10.1159/000531807","url":null,"abstract":"","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136257144","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":"Myrtenol Ameliorates Recognition Memories' Impairment and Anxiety-Like Behaviors Induced by Asthma by Mitigating Hippocampal Inflammation and Oxidative Stress in Rats.","authors":"Mohammad Abbas Bejeshk, Amir Hashem Aminizadeh, Elham Jafari, Sina Motamedi, Iman Zangiabadi, Ahmad Ghasemi, Mazyar Fathi, Akram Nezhadi, Faezeh Akhgarandouz, Fatemeh Bejeshk, Leila Mohammadi, Fatemeh Mohammadi, Mohammad Amin Rajizadeh","doi":"10.1159/000528626","DOIUrl":"10.1159/000528626","url":null,"abstract":"<p><strong>Introduction: </strong>Asthma is related to neurochemical alterations which affect brain functions and lead to anxiety and cognitive dysfunctions. Myrtenol has sparked considerable interest due to its pharmacological effects, especially for the remediation of chronic disorders. Thus, the present research was designed to evaluate the impacts of myrtenol on anxiety-like behaviors, cognitive declines, inflammation, and oxidative stress in the hippocampus of asthmatic rats.</p><p><strong>Methods: </strong>Rats were allocated to five groups: control, asthma, asthma/vehicle, asthma/myrtenol, and asthma/budesonide. Asthma was elicited in the rats by ovalbumin, and the animals were then exposed to myrtenol inhalation. Anxiety-like behavior and memory were assessed by elevated plus maze (EPM) and novel object and location recognition tests. Interleukins (interleukin-6, -17, and -10), tumor necrosis factor α (TNF-α), and oxidative stress biomarkers such as malondialdehyde (MDA), superoxide dismutase (SOD), Glutathione peroxidase (GPX), and total antioxidant capacity (TAC) in the hippocampus were assessed by the ELISA method.</p><p><strong>Results: </strong>The levels of IL-6, IL-17, TNF-α, and MDA decreased, but GPX, SOD, and TAC levels increased in the hippocampus of asthmatic animals due to myrtenol inhalation.</p><p><strong>Conclusion: </strong>Myrtenol diminished asthma-induced anxiety-like behaviors and cognitive deficits in asthmatic rats; these effects might have been typically mediated by a reduction in inflammation and oxidative stress.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":"30 1","pages":"42-54"},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10548859","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}