Translational Neuroscience最新文献

{"title":"Identifying key biomarkers and therapeutic candidates for post-COVID-19 depression through integrated omics and bioinformatics approaches.","authors":"Yi Zhou, Chunhua Yang, Jing Zhou, Qiyao Zhang, Xingling Sui, Hongyu Dong, Haidong Zhang, Yue Wang","doi":"10.1515/tnsci-2022-0360","DOIUrl":"10.1515/tnsci-2022-0360","url":null,"abstract":"<p><strong>Introduction: </strong>Depression, the leading cause of disability worldwide, is known to be exacerbated by severe acute respiratory syndrome coronavirus 2 infection, worsening coronavirus disease 2019 (COVID-19) outcomes. However, the mechanisms and treatments for this comorbidity are not well understood.</p><p><strong>Methods: </strong>This study utilized Gene Expression Omnibus datasets for COVID-19 and depression, combined with protein-protein interaction networks, to identify key genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to understand gene functions. The CIBERSORT algorithm and NetworkAnalyst were used to examine the relationship of immune cell infiltration with gene expression and to predict transcription factors (TFs) and microRNAs (miRNAs) interactions. The Connectivity Map database was used to predict drug interactions with these genes.</p><p><strong>Results: </strong><i>TRUB1</i>, <i>PLEKHA7</i>, and <i>FABP6</i> were identified as key genes enriched in pathways related to immune cell function and signaling. Seven TFs and nineteen miRNAs were found to interact with these genes. Nineteen drugs, including atorvastatin and paroxetine, were predicted to be significantly associated with these genes and potential therapeutic agents for COVID-19 and depression.</p><p><strong>Conclusions: </strong>This research provides new insights into the molecular mechanisms of post-COVID-19 depression and suggests potential therapeutic strategies, marking a step forward in understanding and treating this complex comorbidity.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220360"},"PeriodicalIF":1.8,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717214","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":"Macrophage accumulation in dorsal root ganglion is associated with neuropathic pain in experimental autoimmune neuritis.","authors":"Chunrong Li, Fangzheng Cao, Houwen Zhang, Weijiao Fan, Yifan Cheng, Yao Lou, Yiqi Wang","doi":"10.1515/tnsci-2022-0355","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0355","url":null,"abstract":"<p><strong>Background: </strong>Neuropathic pain is a common symptom of Guillain-Barré syndrome (GBS). The infiltration of macrophages in the dorsal root ganglion (DRG) contributed to neuropathic pain in nerve injury. The underlying mechanisms of neuropathic pain in patients with GBS remain unknown. Experimental autoimmune neuritis (EAN) is a useful mice model of GBS. Our study aimed to explore whether the infiltration of macrophages in DRG is associated with neuropathic pain of EAN.</p><p><strong>Methods: </strong>Male C57BL/6 mice were randomly divided into two groups, the EAN group (<i>n</i> = 12) and the control group (<i>n</i> = 12). Six mice in each group were sacrificed after anesthetization in the attack and remission phase, respectively. The 50% paw withdrawal threshold and clinical score were measured, and macrophages with its subtypes were detected in the spleen and DRG tissue.</p><p><strong>Results: </strong>More macrophages infiltrated the DRG of the EAN group in the attack phase and mostly surrounded neurons in the DRG. The proportion of macrophages and pro-inflammatory macrophages in the spleen of mice with EAN was significantly higher than the control group in the attack phase.</p><p><strong>Conclusion: </strong>The infiltration of macrophages in DRG might be associated with neuropathic pain of EAN and pro-inflammatory macrophages may involve in neuropathic pain of EAN.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220355"},"PeriodicalIF":1.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508708","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":"Cystatin C alleviates unconjugated bilirubin-induced neurotoxicity by promoting bilirubin clearance from neurocytes via exosomes, dependent on hepatocyte UGT1A1 activity.","authors":"Yating Du, Zhenkun Li","doi":"10.1515/tnsci-2022-0357","DOIUrl":"10.1515/tnsci-2022-0357","url":null,"abstract":"<p><p>There is an urgent need to identify effective drugs for the treatment of nerve injury caused by unconjugated bilirubin (UCB). Our previous research found that cystatin C (CST3) alleviates UCB-induced neurotoxicity by promoting autophagy in nerve cells, but that autophagy inhibitors did not completely inhibit the effects of CST3. This study investigated whether CST3 could alleviate the neurotoxicity of UCB by promoting the secretion and transport of exosomes containing UCB to the liver for metabolism. It demonstrated that hyperbilirubinemia mice treated with CST3 had a higher number of serum exosomes than those in hyperbilirubinemia mice treated with phosphate-buffered saline. CST3-mediated protection against UCB-induced damage was abolished when autophagy and extracellular vesicle inhibitors were used in combination. The number of exosomes in the CST3 overexpression group was higher than that in the control group. Molecular docking experiments showed that UCB and CST3 had high docking score (-8.2). These results suggest that UCB may be excreted from cells by exosomes, and CST3 may promote this process by binding to UCB and entering the exosomes. We demonstrated that the effect of CST3 relied on liver cells with normal UDP-glucuronyl transferase1A1 (UGT1A1) activity in a coculture system of HT22 and L02 cells. CST3 levels were lower in exosomes secreted by L02 cells than in those secreted by human umbilical vein endothelial cells (HUVECs), whereas CST3 levels were higher in the culture supernatants of L02 cells than in the culture supernatants of HUVECs. This suggests that UCB exosomes in L02 cells may be released and internalized by CST3 and that UCB is then processed by UGT1A1 to conjugate UCB, thus reducing its toxicity. These results suggest that CST3 might alleviate UCB-induced neurotoxicity by promoting the clearance of UCB from cells via exosomes and that these effects are dependent on UGT1A1 activity in liver cells.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220357"},"PeriodicalIF":1.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475596","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":"Long COVID elevated MMP-9 and release from microglia by SARS-CoV-2 Spike protein.","authors":"Duraisamy Kempuraj, Irene Tsilioni, Kristina K Aenlle, Nancy G Klimas, Theoharis C Theoharides","doi":"10.1515/tnsci-2022-0352","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0352","url":null,"abstract":"<p><strong>Objective: </strong>Long COVID is a major health concern because many patients develop chronic neuropsychiatric symptoms, but the precise pathogenesis is unknown. Matrix metalloproteinase-9 (MMP-9) can disrupt neuronal connectivity and be elevated in patients with long COVID.</p><p><strong>Methods: </strong>In this study, MMP-9 was measured in the serum of long COVID patients and healthy controls, as well as in the supernatant fluid of cultured human microglia cell line stimulated by recombinant severe acute respiratory syndrome coronavirus 2 Spike protein, as well as lipopolysaccharide (LPS) and neurotensin (NT) used as positive controls. MMP-9 was measured by commercial enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>MMP-9 was significantly elevated in the serum of long COVID patients compared to healthy controls. Moreover, there was significant release of MMP-9 from a cultured human microglia cell line stimulated by LPS, NT, or Spike protein. We further show that pretreatment with the flavonoids luteolin and tetramethoxyluteolin (methlut) significantly inhibited the release of MMP-9 stimulated by the Spike protein.</p><p><strong>Conclusion: </strong>MMP-9 from Spike protein-stimulated microglia could contribute to the development of long COVID and may serve as a target for treatment including the use of luteolin.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220352"},"PeriodicalIF":1.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475597","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":"A data science approach to optimize ADHD assessment with the BRIEF-2 questionnaire.","authors":"Lucía Caselles-Pina, Paula Serna Del Amo, David Aguado, Jorge López-Castromán, Juan de Dios Sanjuán-Antúnez, David Delgado-Gómez","doi":"10.1515/tnsci-2022-0349","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0349","url":null,"abstract":"<p><p>Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. A key challenge associated with this condition is achieving an early diagnosis. The current study seeks to anticipate and delineate the assessments offered by both parents and teachers concerning a child's behavior and overall functioning with the Behavior Rating Inventory of Executive Function-2 (BRIEF-2). Mothers, fathers, and teachers of 59 children diagnosed or in the process of being assessed for ADHD participated in this study. The responses provided by 59 mothers, 59 fathers, and 57 teachers to the BRIEF-2 questionnaire were collected. The performance of various feature selection techniques, including Lasso, decision trees, random forest, extreme gradient boosting, and forward stepwise regression, was evaluated. The results indicate that Lasso stands out as the optimal method for our dataset, striking an ideal balance between accuracy and interpretability. A repeated validation analysis reveals an average positive correlation exceeding 0.5 between the inattention/hyperactivity scores reported by informants (mother, father, or teacher) and the predictions derived from Lasso. This performance is achieved using only approximately 18% of the BRIEF-2 items. These findings underscore the usefulness of variable selection techniques in accurately characterizing a patient's condition while employing a small subset of assessment items. This efficiency is particularly valuable in time-constrained settings and contributes to improving the comprehension of ADHD.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220349"},"PeriodicalIF":1.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393546","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":"<i>TTBK2</i> ^T3290C mutation in spinocerebellar ataxia 11 interferes with ciliogenesis.","authors":"Ruiqing Luo, Xiaoxia Zeng, Ping Li, Shuai Hu, Xueliang Qi","doi":"10.1515/tnsci-2022-0353","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0353","url":null,"abstract":"<p><p>This study aimed to elucidate the impact of the <i>TTBK2</i> ^T3290C mutation (MUT) associated with Spinocerebellar Ataxia 11 (SCA11) on TTBK2 expression, function, and ciliogenesis. Lymphocytes were isolated from peripheral blood samples of SCA11 family members with the MUT and healthy controls (wild-type, WT). HEK-293 cells transfected with either WT or MUT <i>TTBK2</i> plasmids were used to assess the MUT's impact on TTBK2 protein expression, enzymatic activity, and its binding to Cep164 protein. Mouse embryonic fibroblast cells transfected with WT or MUT <i>TTBK2</i> plasmids examined the MUT's effect on cilia formation. Clinically, there was no significant difference in the expression of TTBK2 between the SCA11 patients and healthy individuals. The <i>TTBK2</i> ^T3290C MUT did not affect protein expression or enzymatic activity but did reduce ciliary formation in embryonic cells and decreased binding affinity to Cep164. Therefore, our data suggested that the <i>TTBK2</i> ^T3290C MUT in SCA11 may impair ciliogenesis by weakening the interaction with Cep164.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220353"},"PeriodicalIF":1.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393545","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":"In a rodent model of autism, probiotics decrease gut leakiness in relation to gene expression of GABA receptors: Emphasize how crucial the gut-brain axis.","authors":"Rawan M Bin-Khattaf, Abeer M Al-Dbass, Mona Alonazi, Ramesa Shafi Bhat, Sooad Al-Daihan, Afaf K El-Ansary","doi":"10.1515/tnsci-2022-0354","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0354","url":null,"abstract":"<p><strong>Objective: </strong>Rodent models may help investigations on the possible link between autism spectrum disorder and increased permeability of the gastrointestinal (GI) tract since autistic patients frequently manifested GI troubles as comorbidities.</p><p><strong>Methods: </strong>Forty young male western Albino rats, weighing approximately 60-70 g and aged 3-4 weeks, were used. In each of the six experimental groups, eight animals were treated as follows. The mice in the control group (I) received phosphate-buffered saline orally. For 3 days, the animals in the propionic acid (PPA)-treated groups (II and III) were given an oral neurotoxic dose of PPA (250 mg/kg body weight each day). Group II was euthanized after 3 days; however, Group III was left alive to be euthanized alongside the other groups. The animals were kept at 22 ± 1°C and allowed to access water and normal food as needed. Identical dosages of PPA were given to the rats in the three treatment groups (IV, V, and VI), and for 3 weeks, they were given the following treatments: 0.2 g/kg body weight of pure <i>Bifidobacterium infantis</i>, a probiotic mixture of PROTEXIN®, Somerset, UK and pure <i>Lactobacillus bulgaricus</i>, respectively. The six groups underwent measurements of serum zonulin and occludin as variables associated with leaky gut, glutathione, malondialdehyde, and catalase as oxidative stress-related variables, with gamma-aminobutyric acid (GABA) receptor gene expression.</p><p><strong>Results: </strong>This study demonstrated the potential effects of pure or mixed probiotics in lowering zonulin and occludin as markers of increased intestinal permeability, enhancing GABA receptor expression, and reducing oxidative stress as neurotoxic effects of PPA.</p><p><strong>Conclusions: </strong>This study demonstrates that various probiotics protect gut barrier function and could be used to alleviate increased intestinal permeability caused by oxidative stress and impaired GABA signaling as a result of PPA neurotoxicity, addressing the clinical implications of probiotic supplements.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220354"},"PeriodicalIF":1.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393547","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":"Amelioration of behavioral and histological impairments in somatosensory cortex injury rats by limbal mesenchymal stem cell transplantation.","authors":"Ali Derakhshani, Farahnaz Taheri, Nima Geraminia, Lily Mohammadipoor-Ghasemabad, Mansoureh Sabzalizadeh, Farzaneh Vafee, Mohammad Reza Afarinesh, Vahid Sheibani","doi":"10.1515/tnsci-2022-0346","DOIUrl":"10.1515/tnsci-2022-0346","url":null,"abstract":"<p><strong>Introduction: </strong>Cortical lesions can cause major sensory and motor impairments, representing a significant challenge in neuroscience and clinical medicine. Limbal mesenchymal stem cells (LMSCs), renowned for their remarkable ability to proliferate and distinct characteristics within the corneal epithelium, offer a promising opportunity for regenerative treatments. This study aimed to assess whether the transplantation of LMSCs could improve tactile ability in rats with lesions of the barrel cortex.</p><p><strong>Methods: </strong>In this experimental study, we divided 21 rats into three groups: a control group, a lesion group with cortical cold lesion induction but no stem cell treatment, and a group receiving LMSC transplantation following cold lesion induction. We conducted 3-week sensory assessments using a texture discrimination test and an open-field test. We also performed Nissl staining to assess changes on the cellular level.</p><p><strong>Results: </strong>Rats in the LMSC transplantation group demonstrated significant improvements in their ability to discrimination textures during the second and third weeks compared to those in the lesion group. The open-field test results showed an increased exploratory behavior of rats in the LMSC transplantation group by the third week compared to the lesion group. Additionally, Nissl staining revealed cellular alterations in the damaged cortex, with a significant distinction observed between rats in the LMSCs and lesion group.</p><p><strong>Conclusion: </strong>The findings suggest that LMSC transplantation enhances sensory recovery in rats with cortical lesions, particularly their ability to discriminate textures. LMSC transplantation benefits brain tissue reparation after a cold lesion on the somatosensory cortex.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220346"},"PeriodicalIF":1.8,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000729","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":"Activating α7nAChR suppresses systemic inflammation by mitigating neuroinflammation of the medullary visceral zone in sepsis in a rat model.","authors":"Lin Peng, Hongbing Li, Cheng Zhang, Weiwei Jiang","doi":"10.1515/tnsci-2022-0345","DOIUrl":"10.1515/tnsci-2022-0345","url":null,"abstract":"<p><p>Our previous studies have shown that activating α7nAChRs suppresses systemic inflammation and immunity through the cholinergic anti-inflammatory pathway (CAP) in early sepsis. Now that the medullary visceral zone (MVZ) is the center of CAP and responsible for regulating systemic inflammation, what changes will occur in MVZ's pathology and function in sepsis, especially when interfering with α7nAChRs? Does activation of MVZ's α7nAChRs contribute to the inhibition of systemic inflammation? To clarify these issues, we explored the systemic inflammation and immunity state by detecting serum levels of TNF-α, IL-6, HMGB1, sCD14, and CD4⁺CD25⁺Treg and TH17 lymphocytes percentage, meanwhile, we analyzed the apoptosis of cholinergic and catecholaminergic neurons and the expressions of tyrosine hydroxylase (TH) and choline acetyltransferase (CHAT) in MVZ in sepsis and the interfering effects on α7nAChRs. In this study, we found that in sepsis, serum TNF-α, IL-6, HMGB1, sCD14, CD4⁺CD25⁺Treg, and TH17 lymphocytes significantly increased and the ratio of Treg/TH17 significantly decreased, cholinergic and catecholaminergic neurons underwent apoptosis with low expressions of TH and CHAT in MVZ; activation of α7nAChRs not only significantly decreased the levels of septic serum TNF-α, IL-6, HMGB1, sCD14, and TH17 lymphocytes (<i>P</i> ＜ 0.05), but also significantly reduced cholinergic and catecholaminergic neurons' apoptosis, and promoted expressions of TH/CHAT. Our study reveals that sepsis undermines MVZ through neuroinflammation which contributes to the uncontrolled systemic inflammation. Activating central α7nAChRs is not only helpful to restore MVZ's structure and function but also beneficial to subside the inflammatory storm in sepsis. Even if MVZ is damaged in sepsis, cholinergic neurons in MVZ still regulate the systemic inflammation stably.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220345"},"PeriodicalIF":1.8,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000728","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":"Thyroid hormone T3 induces Fyn modification and modulates palmitoyltransferase gene expression through αvβ3 integrin receptor in PC12 cells during hypoxia.","authors":"Elisabed Kvergelidze, Tamar Barbakadze, Judit Bátor, Irine Kalandadze, David Mikeladze","doi":"10.1515/tnsci-2022-0347","DOIUrl":"10.1515/tnsci-2022-0347","url":null,"abstract":"<p><p>Thyroid hormones (THs) are essential in neuronal and glial cell development and differentiation, synaptogenesis, and myelin sheath formation. In addition to nuclear receptors, TH acts through αvβ3-integrin on the plasma membrane, influencing transcriptional regulation of signaling proteins that, in turn, affect adhesion and survival of nerve cells in various neurologic disorders. TH exhibits protective properties during brain hypoxia; however, precise intracellular mechanisms responsible for the preventive effects of TH remain unclear. In this study, we investigated the impact of TH on integrin αvβ3-dependent downstream systems in normoxic and hypoxic conditions of pheochromocytoma PC12 cells. Our findings reveal that triiodothyronine (T3), acting through αvβ3-integrin, induces activation of the JAK2/STAT5 pathway and suppression of the SHP2 in hypoxic PC12 cells. This activation correlates with the downregulation of the expression palmitoyltransferase-ZDHHC2 and ZDHHC9 genes, leading to a subsequent decrease in palmitoylation and phosphorylation of Fyn tyrosine kinase. We propose that these changes may occur due to STAT5-dependent epigenetic silencing of the palmitoyltransferase gene, which in turn reduces palmitoylation/phosphorylation of Fyn with a subsequent increase in the survival of cells. In summary, our study provides the first evidence demonstrating the involvement of integrin-dependent JAK/STAT pathway, SHP2 suppression, and altered post-translational modification of Fyn in protective effects of T3 during hypoxia.</p>","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220347"},"PeriodicalIF":1.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907804","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}