Neurochemical Journal最新文献

{"title":"Isolation of Phytohormone trans-Zeatin: Potential Oxidant Scavenger and Anti-Aging Compound","authors":"Adarsh Kesharwani, Siva Prasad Panda","doi":"10.1134/s1819712424010112","DOIUrl":"https://doi.org/10.1134/s1819712424010112","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>In all parts of the world, dementia rates are rising rapidly, particularly in Western nations, where it accounts for roughly 60% of cases and is linked to population aging. According to the free radical hypothesis of aging, age-related cellular and tissue damages are brought on by free radicals. <i>Cocos nucifera</i> (L<i>.</i>) has been traditionally utilized in various health conditions, including digestive disorders, antifungal, wound healing, immune support, and cardiovascular health. Objective of the research is to isolate, quantify, and characterize <i>trans-</i>Zeatin (tZn) from hydroalcoholic extract of <i>Cocos nucifera</i> (HECN) and to evaluate its anti-aging and antioxidant potential by studying the Keap-1/HO-1 signaling pathway through in-silico docking analysis. UV, IR, HPLC, and NMR techniques were used for isolation and quantification of tZn. The in vitro anti-oxidant potential of tZn was examined, by using the DPPH, OH, and NO radical scavenging assay. Anti-aging potential of tZn was evaluated by docking analysis against selected proteins (Keap-1 and HO-1) using AutoDock Vina software. From the result it was found that tZn has strong antioxidant potential in a concentration dependent manner with IC₅₀ values of 13.86 ± 2.8, 15.49 ± 3.2, and 16.96 ± 1.5 µg/mL comparable with reference standard ascorbic acid. The molecular docking analysis showed the significant binding potential of the tZn with the active sites of Keap-1 and HO-1, which are crucially involved in the pathophysiology of aging. Based on the conducted studiеs, it is concluded that the tZn from HECN could be measured as a potential anti-oxidant and anti-aging compound.</p>","PeriodicalId":19119,"journal":{"name":"Neurochemical Journal","volume":"26 1","pages":""},"PeriodicalIF":0.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141152503","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":"High Expression of lncRNA XIST Assists in the Diagnosis of Parkinson’s Disease","authors":"Liang Zhang, Guoping Li, Dingci Lu, Qihe Dai","doi":"10.1134/s1819712424010276","DOIUrl":"https://doi.org/10.1134/s1819712424010276","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Long non-coding RNA (lncRNA) XIST has been implicated in the development of PD. Herein, we sought to investigate the diagnostic value of serum XIST expression in PD. We recorded clinical baseline data, including age, sex, body mass index (BMI), years of education, and PD family history, for PD patients and healthy controls, in addition to the disease course in PD patients. The disease severity of PD patients was assessed using the Hoehn-Yahr grading scale. We evaluated serum XIST expression levels in PD patients and healthy controls using RT-qPCR and assessed the correlation between serum XIST expression and the Unified Parkinson’s Disease Rating Scale (UPDRS) score. Additionally, we used receiver operating characteristic (ROC) curve to determine the diagnostic value of XIST expression for PD. Our results showed no significant differences in age, sex, BMI, and years of education between PD patients and healthy controls. However, more PD patients had a family history of PD. We found that serum XIST expression was significantly up-regulated in PD patients, and its levels were positively correlated with the UPDRS score. Higher PD stage was also associated with increased serum XIST expression. ROC analysis revealed that XIST expression had a diagnostic value for PD. In conclusion, our findings suggest that serum lncRNA XIST expression may serve as a potential diagnostic biomarker for PD.</p>","PeriodicalId":19119,"journal":{"name":"Neurochemical Journal","volume":"46 1","pages":""},"PeriodicalIF":0.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141152510","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":"Extracellular Vesicles Secreted by the Activated THP-1 Cells Influence the Inflammation Gene Expression in Zebrafish","authors":"D. B. Sambur, O. V. Kalinina, A. D. Aquino, P. V. Tirikova, M. A. Migunova, E. E. Koroleva, A. S. Trulioff, A. A. Rubinshtein, I. V. Kudryavtsev, A. S. Golovkin","doi":"10.1134/s1819712424010197","DOIUrl":"https://doi.org/10.1134/s1819712424010197","url":null,"abstract":"<p><b>Abstract</b>—Extracellular vesicles secreted by immune cells may play a significant role in the initiation, maintenance, and progression of systemic inflammation. The aim of the study was to investigate the regulatory effect of extracellular vesicles (EVs) produced by activated monocyte-like THP-1 cells on expression levels of inflammatory genes in a zebrafish. Real-time PCR analysis was performed to investigate the relative expression levels of <i>il-1</i>β, <i>il-6</i>, <i>tnf-</i>α, <i>ifn-</i>γ, <i>mpeg-1.1</i>, <i>mpeg-1.2</i>, <i>mpx</i>, and <i>il-10</i> genes in the brain, liver, and heart of zebrafish followed by intracelomic injection of EVs produced by THP-1 cells activated with tumor necrosis factor (TNF) and phorbol-12-myristate-13-acetate (PMA) at different concentrations. EVs, secreted by THP-1 cells activated with TNF at a concentration of 10 ng/mL and PMA at concentrations of 16 and 50 ng/mL, reduced the expression levels of <i>il-1</i>β, <i>ifn-</i>γ, <i>tnf-</i>α, <i>mpx</i>, <i>mpeg-1.1</i>, <i>mpeg-1.2</i>, and <i>il-10</i> genes in the brain, heart and liver of <i>Danio rerio</i>. EVs secreted by THP-1 cells treated with TNF at doses of 10 and 20 ng/mL had opposite effects on the gene expression levels of <i>il-1</i>β in the brain<i>, il-1</i>β<i>, il-10</i>, and <i>il-6</i> in the heart; on <i>il-1</i>β, <i>il-10</i>, <i>mpx</i>, and <i>mpeg-1.2</i> in the liver. EVs secreted by THP-1 cells treated with PMA at doses of 16 and 50 ng/mL had opposite effects on the expression levels of <i>il-6</i> and <i>il-10</i> genes in the heart and <i>ifn-</i>γ gene in the liver. EVs produced by activated THP-1 cells have a systemic effect on <i>Danio rerio</i> manifested as changes in the expression of pro- and anti-inflammatory cytokine genes in the brain, liver, and heart. The qualitative composition of the EVs produced by activated THP-1 cells varies depending on the type and dose of the used stimulus, which reflects on strength and direction of the effects detected <i>in vivo</i>.</p>","PeriodicalId":19119,"journal":{"name":"Neurochemical Journal","volume":"19 1","pages":""},"PeriodicalIF":0.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141152532","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":"Evaluation of Paraoxonase, Arylesterase, Dipeptidyl Peptidase-IV, Oxidative Stress, and Oxidative DNA Damage in Patients with Obsessive-Compulsive Disorder","authors":"Eser Sağaltıcı, Hasan Belli, Aysegul Kirankaya, Hüseyin Köse, Cenk Ural, Mustafa Nuray Namlı, Onur Okan Demirci, Hasan Gökçay","doi":"10.1134/s1819712424010173","DOIUrl":"https://doi.org/10.1134/s1819712424010173","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Some findings have emerged from the field of oxidative stress in patients with psychiatric disorders. These date also state that oxidative balance and obsessive-compulsive disorder (OCD) are significantly related. Yet, researchers have not investigated oxidative stress, oxidative balance, and DNA damage together. We tested the levels of paraoxonase-1 (PON1), and arylesterase (ARE). We also tested the dipeptidyl peptidase-IV (DPP-IV), oxidative stress, and oxidative DNA damage. We enrolled 37 patients with OCD in the study. The diagnosis of OCD according to DSM-V criteria was established. Patients had not received treatment for at least 6 months. The controls were matched with the patients about sex, age, body mass index (BMI), and smoking. Clinicians used the sociodemographic information form. All subjects were evaluated with a semi-structured questionnaire. Serum PON1, ARE, DPP-IV, oxidative stress index (OSI), and 8‑hydroxideoxiguanosine (8-OHdG) calculations were conducted in the biochemical laboratory. PON1 and DPP-IV levels were not different between OCD patients and the control group (<i>P</i> &gt; 0.05). An oxidative DNA damage marker 8-OHdG—and OSI were higher in the patient’s group (<i>p</i> &lt; 0.05). But levels of ARE were significantly lower in OCD patients (<i>P</i> &lt; 0.05). We found evidence that oxidative stress-induced parameters such as OSI, ARE, and 8-OHdG might be related to a specific pathologic state in patients with OCD. The findings may provide a rationale for treating the pathological processes.</p>","PeriodicalId":19119,"journal":{"name":"Neurochemical Journal","volume":"46 1","pages":""},"PeriodicalIF":0.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141152533","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":"Hydrogen Sulfide Ameliorates Homocysteine-Induced Mitochondrial Autophagy Disorder in HT22 Cells","authors":"Haijun Wei, Juan He, Xing Li, Mei Zhao, Fan Xiao","doi":"10.1134/s1819712424010252","DOIUrl":"https://doi.org/10.1134/s1819712424010252","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Damaged mitochondrial autophagy (mitophagy) caused by the elevated level of homocysteine (Hcy) or hyperhomocysteine (Hhcy) is closely related to neurodegenerative diseases. However, effective intervening strategies for Hcy-mediated impaired mitophagy have not been discovered. Hydrogen sulfide (H₂S) act as a third gaseous modulator with neuroprotective and anti-oxidative properties. Here we hypothesized that the use of hydrogen sulfide in an in vitro model would ameliorate Hcy-induces mitotic dysfunction. The mouse hippocampal neuronal cell line (HT22) was pretreated with two concentrations (100, 200 μM) of NaHS before exposure to Hcy. The expression of autophagy related proteins, including Beclin-1, LC3-II, P62, was determined by western blotting. To evaluate mitochondrial function, mitochondrial membrane potential was monitored by flow cytometry after tetramethylrhodamine (TMRM) staining. The number of damaged mitochondria was also analyzed by flow cytometry after Mito-Tracker Red (MTR) staining. Our results demonstrated that Hcy caused significant down-regulation of Beclin-1, LC3-II, and up-regulation of P62, compared to normal cells (not pretreated with NaHS and not exposed to Hcy). However, hydrogen sulfide partially reversed the expression of the above three proteins in a dose-dependent manner. In addition, the Hcy-induced impaired mitochondrial membrane potential and impaired number were restored by pretreatment with NaHS. Taken together, hydrogen sulfide ameliorates Hcy-mediated mitochondrial phagocytic dysfunction and may serve as a potential interventional strategy to counteract the detrimental effects of Hcy on mitochondrial phagocytosis in neurodegenerative conditions.</p>","PeriodicalId":19119,"journal":{"name":"Neurochemical Journal","volume":"14 1","pages":""},"PeriodicalIF":0.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141152505","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 Ameliorative Effects of Naringin on Cisplatin-Induced Neurotoxicity in SH-SY5Y Neuroblastoma Cells","authors":"Pinar Bayram, Selina Aksak Karamese","doi":"10.1134/s1819712424010094","DOIUrl":"https://doi.org/10.1134/s1819712424010094","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>In this study, our aim was to investigate the potential therapeutic effects of different doses of naringin on SH-SY5Y neuroblastoma cells by effecting the 3 different cellular processes: (i) apoptosis, (ii) inflammation, and (iii) oxidative stress. For this reason, we performed ELISA to detect the levels/positivity of IL-1-beta, IL-6, IL-10, TGF-beta, SOD, CAT, LPO, VEGF, caspase-3 and caspase-9. Our study was designed as groups in which control, only cisplatin, only naringin and cisplatin with naringin co-incubated groups. In cisplatin and naringin co-incubated groups, cisplatin was applied on SH-SY5Y neuroblastoma cells for 2 h and then co-incubated with appropriate doses of naringin. In the without cisplatin groups, only naringin was administered. CVDK-8 was used for cell viability and FDA-PI immunofluorescent dyes were used to determine the ratio of dead and viable cells. For ELISA; the culture media of all experimental groups were collected and the levels of TGF-beta, IL-10, IL-6 and IL-1-beta, caspase-3, caspase-9, VEGF, SOD, CAT and LPO were determined. Immunofluorescence staining results were also in line with the viability analysis results and neurotoxicity was inhibited at the best 25 µM dose. When the ELISA results are examined, it was seen that Cisplatin caused an important increase in the levels of pro-inflammatory cytokines, caspase-3, caspase-9, and the activities of SOD, CAT, LPO enzymes, while naringin application reduced the levels of mentioned parameters in different doses. Naringin was able to balance the activities of oxidative and anti-oxidant enzymes, suppress inflammation, apoptosis and metastasis. Although it has various beneficial effects on neurotoxicity models, further molecular studies should be performed for better understanding the mechanism of naringin effects.</p>","PeriodicalId":19119,"journal":{"name":"Neurochemical Journal","volume":"15 1","pages":""},"PeriodicalIF":0.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141152528","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 Effect of Prenatal Stress on the Levels of Nitric Oxide Metabolites in the CNS","authors":"O. N. Kuleshova, D. D. Teplyi, E. D. Bazhanova","doi":"10.1134/s1819712424010136","DOIUrl":"https://doi.org/10.1134/s1819712424010136","url":null,"abstract":"<p><b>Abstract</b>—Nitric oxide has several important functions in the CNS. This neurotransmitter regulates apoptotic processes, differentiation and proliferation of neurons, synaptic activity and plasticity. Stress during the intrauterine period may be a factor influencing the level of NO in various regions of the CNS. The aim of the study was to investigate the levels of NO metabolites in phylogenetically different structures of the CNS in mature male and female rats at various stages estrous cycle, which were subjected to prenatal stress. Twelve pregnant female rats were exposed to stress on gestation days 16–19 for 3 h in the morning. The NO level was estimated in adult 4-month-old offspring of both sexes. In male rats, the decreased levels of NO metabolites were observed in the cerebellum and hypothalamus whereas in the spinal cord, it was increased. In control females, the levels of NO metabolites were higher in all CNS regions compared to males while after prenatal stress, they changed to a lesser extent. Significant differences were revealed in the spinal cord irrespectively of the estrous cycle and in the cerebellum, at the estrus stage. Finally, regardless of sex, the phylogenetically younger cerebral cortex, was the most resilient to prenatal stress whereas the most pronounced changes were revealed in the phylogenetically ancient region of the CNS such as the spinal cord. Taking into account the importance of NO as a key signaling molecule in the CNS, any changes in its level after prenatal stress may have both adaptive and negative consequences for functional condition of the tissue.</p>","PeriodicalId":19119,"journal":{"name":"Neurochemical Journal","volume":"54 1","pages":""},"PeriodicalIF":0.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141152529","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":"Markers of Inflammation, Energy and Glutamate Metabolism, and Antioxidant Defense in Patients with Adolescent Depression","authors":"S. A. Zozulya, O. K. Savushkina, T. A. Prokhorova, E. B. Tereshkina, I. S. Boksha, M. A. Omelchenko, T. P. Klyushnik","doi":"10.1134/s1819712424010288","DOIUrl":"https://doi.org/10.1134/s1819712424010288","url":null,"abstract":"<p><b>Abstract</b>—The involvement of inflammation, disturbances of glutamate metabolism, and oxidative stress in the pathogenesis of schizophrenia and affective disorders has been proven by numerous studies. It seems relevant to assess the role of these systems in the development of prodromal stages of schizophrenia in juvenile patients with depression. The aim of this study was to investigate the association between markers of inflammation, energy and glutamate metabolism, and antioxidant defense with the clinical features of patients with adolescent depression. 74 males aged 16–25 years with a first depressive episode (F32.1-2, F32.38, F32.8) were observed: 32 subjects with attenuated positive symptoms, 22 persons with attenuated negative symptoms, 20 individuals without attenuated schizophrenia symptoms. The control group included 57 mentally healthy adults aged 19–25 years. The activity of leukocyte elastase and α1-proteinase inhibitor, the level of autoantibodies to S100B and myelin basic protein in plasma and the activity of cytochrome <i>c</i>-oxidase, glutamate dehydrogenase, glutathione reductase and glutathione-S-transferase in platelets were determined. Within each clinical group, differences in the profiles of immunological and biochemical parameters were identified. Division of patients into clusters according to all biological parameters showed different level of inflammation and changes of glutamate metabolism and antioxidant defense related to the features of psychopathological symptoms. The results confirm the connection of the studied metabolic systems and their different involvement to the development of adolescent depression with different psychopathological structure, which is important to assess the role of these systems in the trajectory of the disease and early therapeutic correction.</p>","PeriodicalId":19119,"journal":{"name":"Neurochemical Journal","volume":"9 1","pages":""},"PeriodicalIF":0.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141152557","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":"Levels of Brain-Derived Neurotrophic Factor (BDNF) and Ciliary Neurotrophic Factor (CNTF) in Blood and Tears of Young and Middle-Aged Patients with Vascular Cognitive Impairment and Depression","authors":"A. A. Gudkova, T. A. Druzhkova, M. S. Zinchuk","doi":"10.1134/s1819712424010306","DOIUrl":"https://doi.org/10.1134/s1819712424010306","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The influence of neurotrophic factors on the development of vascular cognitive impairment (VCI) and depression has been investigated in a large number of studies. Changes in BDNF levels and its role in the development of cognitive impairment and depression are similar in many ways. However, to date, there is no clear understanding of the mechanisms of BDNF involvement in the development of VCI and depression. Even less data, mainly experimental, are available on the influence of CNTF on the development of cognitive disorders and depression, although its role in their genesis is considered indisputable. The aim of the study was to investigate the levels of BDNF and CNTF in blood and tears of patients with VCI and depression. The study included 324 people admitted to the Moscow Research and Clinical Center for Neuropsychiatry (MRCCN) and healthy controls from January 2017 to March 2023. Participants were divided into four groups: (1) vascular mild cognitive impairment without depression (113 patients, mean age 71.1 ± 9.74 years); (2) vascular dementia without depression (69 patients, mean age 70.7 ± 8.59 years); (3) depression without cognitive impairment (102 patients, mean age 30.7 ± 10.21 years); (4) healthy controls (40 participants, mean age 47.6 ± 22.01 years). All patients underwent neurological and psychiatric examination including Beck depression inventory, Mini International Neuropsychiatric Interview (M.I.N.I.), Montreal Cognitive Assessment Test (MoCA), and Mini-Mental State Examination (MMSE), magnetic resonance imaging (MRI), BDNF and CNTF levels assessment in serum and lacrimal fluid. For statistical analysis we used Mann-Whitney U-test, chi-squared test, Spearman rank correlation. The level of significance <i>p</i> &lt; 0.05. In VCI patients, decreased BDNF levels in blood and tears are observed in dementia. The level of CNTF in tears is significantly lower in MCI and dementia than in healthy individuals of the same age. In people without cognitive impairment and in MCI there is a significant negative correlation of blood BDNF level with age, in dementia this correlation is lost. In depression in young and middle-aged people, there is no correlation of blood BDNF levels with age. In depression, the positive correlation between blood and tear BDNF levels present in healthy young and middle-aged individuals is lost. Blood and tear BDNF levels and their correlations do not differ in patients with unipolar and bipolar depressive disorders. Young and middle-aged depressed patients with depression have elevated levels of CNTF in blood and tears compared to healthy individuals of the same age, but as in non-depressed individuals, there is no significant correlation between CNTF in blood and CNTF in tears. There is no correlation between BDNF and CNTF levels in blood and tears in healthy young and middle-aged individuals and in depressed patients of the same age.</p>","PeriodicalId":19119,"journal":{"name":"Neurochemical Journal","volume":"221 1","pages":""},"PeriodicalIF":0.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141152559","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":"Reduced REST Expression in Neural Progenitor Cells, Adult Cortex, and Impaired REST Nuclear Translocation in the Prefrontal Cortex of Ts1Cje Mouse Model of Down Syndrome","authors":"Chong-Teik Lim, Xin-Jieh Lam, Arthini-Arrumugam Crystal, Tan Huang, Norhazlin Jusoh, Pike-See Cheah, King-Hwa Ling","doi":"10.1134/s1819712424010148","DOIUrl":"https://doi.org/10.1134/s1819712424010148","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Down syndrome (DS) is a common genetic disorder caused by trisomy of human chromosome 21. DS individuals have neurodevelopmental defects that lead to the manifestation of neurological and neuropsychiatric disorders. Repressor element-1 silencing transcription factor (REST) is the key epigenetic neuronal gene expression regulator. A comprehensive spatiotemporal profiling of <i>REST</i> expression is needed to understand its role in DS brain development. Therefore, we characterised REST targets in this study and profiled its expression using the brain samples from Ts1Cje, a mouse model exhibiting DS neuropathology. Over-representation analysis of Ts1Cje differentially expressed genes (DEGs) with mouse REST targets was performed. The cerebral cortex, hippocampus, and cerebellum of Ts1Cje and wildtype (WT) mice were procured at postnatal—P1, P15, P30, and P84 and embryonic—E14 and P1.5 development timepoints. RNAs from the brain tissues and cultured neurospheres were analysed with qPCR to determine the spatiotemporal profile of <i>Rest</i> expression. Western blot and immunohistochemistry (IHC) staining were performed to assess the level of REST expression and nuclear localisation. Over-representation analysis showed the Ts1Cje DEGs were significantly overlapped with mouse REST target genes. QPCR and Western blot analysis revealed a significant downregulation of <i>Rest</i> transcript in neurospheres and protein in Ts1Cje compared to WT. IHC staining showed REST perinuclear marginalisation and significantly reduced nuclear REST expression in the Ts1Cje prefrontal cortex. Loss of functional REST repression may lead to de-repression of DEGs in the Ts1Cje brain, potentially leading to various neuropathology seen in the Ts1Cje or DS brain.</p>","PeriodicalId":19119,"journal":{"name":"Neurochemical Journal","volume":"53 1","pages":""},"PeriodicalIF":0.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141152498","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}