Experimental Neurobiology最新文献_第10页

Chronic Restraint Stress Decreases the Excitability of Hypothalamic POMC Neuron and Increases Food Intake. 慢性约束应激降低下丘脑POMC神经元的兴奋性，增加食物摄入量。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2021-12-31 DOI: 10.5607/en21037

Go Eun Ha, Eunji Cheong

{"title":"Chronic Restraint Stress Decreases the Excitability of Hypothalamic POMC Neuron and Increases Food Intake.","authors":"Go Eun Ha, Eunji Cheong","doi":"10.5607/en21037","DOIUrl":"https://doi.org/10.5607/en21037","url":null,"abstract":"Stress activates the hypothalamic-pituitary-adrenal system, and induces the release of glucocorticoids, stress hormones, into circulation. Many studies have shown that stress affects feeding behavior, however, the underlying circuitry and molecular mechanisms are not fully understood. The balance between orexigenic (simulating appetite) and anorexigenic (loss of appetite) signals reciprocally modulate feeding behavior. It is suggested that proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons in the arcuate nucleus (ARC) of the hypothalamus are the first-order neurons that respond to the circulating signals of hunger and satiety. Here, we examined a chronic restraint stress model and observed an increase in food intake, which was not correlated with anhedonia. We investigated whether stress affects the properties of POMC and NPY neurons and found that chronic restraint stress reduced the excitatory inputs onto POMC neurons and increased the action potential threshold. Therefore, our study suggests that chronic stress modulates the intrinsic excitability and excitatory inputs in POMC neurons, leading to changes in feeding behavior.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"30 6","pages":"375-386"},"PeriodicalIF":2.4,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5d/43/en-30-6-375.PMC8752322.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39785314","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}

引用次数: 4

Oleanolic Acid Inhibits Neuronal Pyroptosis in Ischaemic Stroke by Inhibiting miR-186-5p Expression. 齐墩果酸通过抑制miR-186-5p表达抑制缺血性脑卒中神经元焦亡。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2021-12-31 DOI: 10.5607/en21006

Shi-Chang Cai, Xiu-Ping Li, Xing Li, Gen-Yun Tang, Li-Ming Yi, Xiang-Shang Hu

{"title":"Oleanolic Acid Inhibits Neuronal Pyroptosis in Ischaemic Stroke by Inhibiting miR-186-5p Expression.","authors":"Shi-Chang Cai, Xiu-Ping Li, Xing Li, Gen-Yun Tang, Li-Ming Yi, Xiang-Shang Hu","doi":"10.5607/en21006","DOIUrl":"https://doi.org/10.5607/en21006","url":null,"abstract":"Ischaemic stroke is a common condition leading to human disability and death. Previous studies have shown that oleanolic acid (OA) ameliorates oxidative injury and cerebral ischaemic damage, and miR-186-5p is verified to be elevated in serum from ischaemic stroke patients. Herein, we investigated whether OA regulates miR-186-5p expression to control neuroglobin (Ngb) levels, thereby inhibiting neuronal pyroptosis in ischaemic stroke. Three concentrations of OA (0.5, 2, or 8 μM) were added to primary hippocampal neurons subjected to oxygen-glucose deprivation/reperfusion (OGD/R), a cell model of ischaemic stroke. We found that OA treatment markedly inhibited pyroptosis. qRT-PCR and western blot revealed that OA suppressed the expression of pyroptosis-associated genes. Furthermore, OA inhibited LDH and proinflammatory cytokine release. In addition, miR-186-5p was downregulated while Ngb was upregulated in OA-treated OGD/R neurons. MiR-186-5p knockdown repressed OGD/R-induced pyroptosis and suppressed LDH and inflammatory cytokine release. In addition, a dual luciferase reporter assay confirmed that miR-186-5p directly targeted Ngb. OA reduced miR-186-5p to regulate Ngb levels, thereby inhibiting pyroptosis in both OGD/R-treated neurons and MCAO mice. In conclusion, OA alleviates pyroptosis in vivo and in vitro by downregulating miR-186-5p and upregulating Ngb expression, which provides a novel theoretical basis illustrating that OA can be considered a drug for ischaemic stroke.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"30 6","pages":"401-414"},"PeriodicalIF":2.4,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/0e/en-30-6-401.PMC8752321.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39785737","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}

引用次数: 2

Hyperoxygenation Ameliorates Stress-induced Neuronal and Behavioral Deficits. 高氧可改善应激诱导的神经元和行为缺陷。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2021-12-31 DOI: 10.5607/en21029

Juli Choi, Hye-Jin Kwon, Ju-Young Seoh, Pyung-Lim Han

{"title":"Hyperoxygenation Ameliorates Stress-induced Neuronal and Behavioral Deficits.","authors":"Juli Choi, Hye-Jin Kwon, Ju-Young Seoh, Pyung-Lim Han","doi":"10.5607/en21029","DOIUrl":"https://doi.org/10.5607/en21029","url":null,"abstract":"Hyperoxygenation therapy remediates neuronal injury and improves cognitive function in various animal models. In the present study, the optimal conditions for hyperoxygenation treatment of stress-induced maladaptive changes were investigated. Mice exposed to chronic restraint stress (CRST) produce persistent adaptive changes in genomic responses and exhibit depressive-like behaviors. Hyperoxygenation treatment with 100% O2 (HO2) at 2.0 atmospheres absolute (ATA) for 1 h daily for 14 days in CRST mice produces an antidepressive effect similar to that of the antidepressant imipramine. In contrast, HO2 treatment at 2.0 ATA for 1 h daily for shorter duration (3, 5, or 7 days), HO2 treatment at 1.5 ATA for 1 h daily for 14 days, or hyperbaric air treatment at 2.0 ATA (42% O2) for 1 h daily for 14 days is ineffective or less effective, indicating that repeated sufficient hyperoxygenation conditions are required to reverse stress-induced maladaptive changes. HO2 treatment at 2.0 ATA for 14 days restores stress-induced reductions in levels of mitochondrial copy number, stress-induced attenuation of synaptophysin-stained density of axon terminals and MAP-2-staining dendritic processes of pyramidal neurons in the hippocampus, and stress-induced reduced hippocampal neurogenesis. These results suggest that HO2 treatment at 2.0 ATA for 14 days is effective to ameliorate stress-induced neuronal and behavioral deficits.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"30 6","pages":"415-429"},"PeriodicalIF":2.4,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c3/6c/en-30-6-415.PMC8752323.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39785738","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}

引用次数: 1

Overexpression of SIRT3 Suppresses Oxidative Stress-induced Neurotoxicity and Mitochondrial Dysfunction in Dopaminergic Neuronal Cells. SIRT3过表达抑制多巴胺能神经元细胞氧化应激诱导的神经毒性和线粒体功能障碍。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2021-10-31 DOI: 10.5607/en21021

Shinrye Lee, Yu-Mi Jeon, Myungjin Jo, Hyung-Jun Kim

{"title":"Overexpression of SIRT3 Suppresses Oxidative Stress-induced Neurotoxicity and Mitochondrial Dysfunction in Dopaminergic Neuronal Cells.","authors":"Shinrye Lee, Yu-Mi Jeon, Myungjin Jo, Hyung-Jun Kim","doi":"10.5607/en21021","DOIUrl":"https://doi.org/10.5607/en21021","url":null,"abstract":"Sirtuin 3 (SIRT3), a well-known mitochondrial deacetylase, is involved in mitochondrial function and metabolism under various stress conditions. In this study, we found that the expression of SIRT3 was markedly increased by oxidative stress in dopaminergic neuronal cells. In addition, SIRT3 overexpression enhanced mitochondrial activity in differentiated SH-SY5Y cells. We also showed that SIRT3 overexpression attenuated rotenoneor H2O2-induced toxicity in differentiated SH-SY5Y cells (human dopaminergic cell line). We further found that knockdown of SIRT3 enhanced rotenone- or H2O2-induced toxicity in differentiated SH-SY5Y cells. Moreover, overexpression of SIRT3 mitigated cell death caused by LPS/IFN-γ stimulation in astrocytes. We also found that the rotenone treatment increases the level of SIRT3 in Drosophila brain. We observed that downregulation of sirt2 (Drosophila homologue of SIRT3) significantly accelerated the rotenone-induced toxicity in flies. Taken together, these findings suggest that the overexpression of SIRT3 mitigates oxidative stress-induced cell death and mitochondrial dysfunction in dopaminergic neurons and astrocytes.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"30 5","pages":"341-355"},"PeriodicalIF":2.4,"publicationDate":"2021-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/62/07/en-30-5-341.PMC8572659.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39679958","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}

引用次数: 14

A Deafness Associated Protein TMEM43 Interacts with KCNK3 (TASK-1) Two-pore Domain K⁺ (K2P) Channel in the Cochlea. 耳聋相关蛋白TMEM43与耳蜗KCNK3 (TASK-1)双孔结构域K+ (K2P)通道相互作用

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2021-10-31 DOI: 10.5607/en21028

Minwoo Wendy Jang, Tai Young Kim, Kushal Sharma, Jea Kwon, Eunyoung Yi, C Justin Lee

{"title":"A Deafness Associated Protein TMEM43 Interacts with KCNK3 (TASK-1) Two-pore Domain K+ (K2P) Channel in the Cochlea.","authors":"Minwoo Wendy Jang, Tai Young Kim, Kushal Sharma, Jea Kwon, Eunyoung Yi, C Justin Lee","doi":"10.5607/en21028","DOIUrl":"https://doi.org/10.5607/en21028","url":null,"abstract":"The TMEM43 has been studied in human diseases such as arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC5) and auditory neuropathy spectrum disorder (ANSD). In the heart, the p.(Ser358Leu) mutation has been shown to alter intercalated disc protein function and disturb beating rhythms. In the cochlea, the p.(Arg372Ter) mutation has been shown to disrupt connexin-linked function in glia-like supporting cells (GLSs), which maintain inner ear homeostasis for hearing. The TMEM43-p.(Arg372Ter) mutant knock-in mice displayed a significantly reduced passive conductance current in the cochlear GLSs, raising a possibility that TMEM43 is essential for mediating the passive conductance current in GLSs. In the brain, the two-pore-domain potassium (K2P) channels are generally known as the \"leak channels\" to mediate background conductance current, raising another possibility that K2P channels might contribute to the passive conductance current in GLSs. However, the possible association between TMEM43 and K2P channels has not been investigated yet. In this study, we examined whether TMEM43 physically interacts with one of the K2P channels in the cochlea, KCNK3 (TASK-1). Utilizing co-immunoprecipitation (IP) assay and Duolink proximity ligation assay (PLA), we revealed that TMEM43 and TASK-1 proteins could directly interact. Genetic modifications further delineated that the intracellular loop domain of TMEM43 is responsible for TASK-1 binding. In the end, gene-silencing of Task-1 resulted in significantly reduced passive conductance current in GLSs. Together, our findings demonstrate that TMEM43 and TASK-1 form a protein-protein interaction in the cochlea and provide the possibility that TASK-1 is a potential contributor to the passive conductance current in GLSs.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"30 5","pages":"319-328"},"PeriodicalIF":2.4,"publicationDate":"2021-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b0/0c/en-30-5-319.PMC8572660.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39679956","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}

引用次数: 5

Precision Capsular Infarct Modeling to Produce Hand Motor Deficits in Cynomolgus Macaques. 精确荚膜梗死模型在食蟹猕猴中产生手部运动缺陷。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2021-10-31 DOI: 10.5607/en21026

Hyung-Sun Kim, Jeong Ho Hwang, Su-Cheol Han, Goo-Hwa Kang, Ji-Young Park, Hyoung-Ihl Kim

{"title":"Precision Capsular Infarct Modeling to Produce Hand Motor Deficits in Cynomolgus Macaques.","authors":"Hyung-Sun Kim, Jeong Ho Hwang, Su-Cheol Han, Goo-Hwa Kang, Ji-Young Park, Hyoung-Ihl Kim","doi":"10.5607/en21026","DOIUrl":"https://doi.org/10.5607/en21026","url":null,"abstract":"Stroke research in non-human primates (NHPs) with gyrencephalic brains is a critical step in overcoming the translational barrier that limits the development of new pharmaceutical and rehabilitative strategies for stroke. White-matter stroke (WMS) has a unique pathophysiology from gray-matter stroke and is not well understood because of a lack of pertinent animal models. To create a precise capsular infarct model in the cynomolgus macaque, we first used electrical stimulation to map hand movements, followed by viral tracing of the hand motor fibers (hMFs). This enabled us to identify stereotactic targets in the posterior limb of the internal capsule (PLIC). Neural tracing showed that hMFs occupy the full width of the PLIC, owing to overlap with the motor fibers for the leg. Furthermore, the hMFs were distributed in an oblique shape, requiring coronal tilting of the target probe. We used the photothrombotic infarct lesioning technique to precisely destroy the hMFs within the internal capsule. Double-point infarct lesioning that fully compromised the hMFs resulted in persistent hand motor and walking deficits whereas single-point lesioning did not. Minor deviations in targeting failed to produce persistent motor deficits. Accurate stereotactic targeting with thorough involvement of motor fibers is critical for the production of a capsular infarct model with persistent motor deficits. In conclusion, the precision capsular infarct model can be translated to the NHP system to show persistent motor deficits and may be useful to investigate the mechanism of post-stroke recovery as well as to develop new therapeutic strategies for the WMS.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"30 5","pages":"356-364"},"PeriodicalIF":2.4,"publicationDate":"2021-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f6/e5/en-30-5-356.PMC8572658.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39679959","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}

引用次数: 0

Diffusion Measure Changes of Substantia Nigra Subregions and the Ventral Tegmental Area in Newly Diagnosed Parkinson's Disease. 新诊断帕金森病患者黑质亚区和腹侧被盖区的弥散测量变化。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2021-10-31 DOI: 10.5607/en21025

Jae-Hyuk Shim, Hyeon-Man Baek

{"title":"Diffusion Measure Changes of Substantia Nigra Subregions and the Ventral Tegmental Area in Newly Diagnosed Parkinson's Disease.","authors":"Jae-Hyuk Shim, Hyeon-Man Baek","doi":"10.5607/en21025","DOIUrl":"https://doi.org/10.5607/en21025","url":null,"abstract":"Historically, studies have extensively examined the basal ganglia in Parkinson's disease for specific characteristics that can be observed with medical imaging. One particular methodology used for detecting changes that occur in Parkinson's disease brains is diffusion tensor imaging, which yields diffusion indices such as fractional anisotropy and radial diffusivity that have been shown to correlate with axonal damage. In this study, we compare the diffusion measures of basal ganglia structures (with substantia nigra divided into subregions, pars compacta, and pars reticula), as well as the diffusion measures of the diffusion tracts that pass through each pair of basal ganglia structures to see if significant differences in diffusion measures can be observed in structures or tracts in newly diagnosed Parkinson's disease patients. Additionally, we include the ventral tegmental area, a structure connected to various basal ganglia structures affected by dopaminergic neuronal loss and have historically shown significant alterations in Parkinson's disease, in our analysis. We found significant fractional anisotropy differences in the putamen, and in the diffusion tracts that pass through pairs of both substantia nigra subregions, subthalamic nucleus, parabrachial pigmental nucleus, ventral tegmental area. Additionally, we found significant radial diffusivity differences in diffusion tracts that pass through the parabrachial nucleus, putamen, both substantia nigra subregions, and globus pallidus externa. We were able to find significant diffusion measure differences in structures and diffusion tracts, potentially due to compensatory mechanisms in response to dopaminergic neuronal loss that occurs in newly diagnosed Parkinson's disease patients.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"30 5","pages":"365-373"},"PeriodicalIF":2.4,"publicationDate":"2021-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7c/05/en-30-5-365.PMC8572662.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39679961","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}

引用次数: 1

Upregulation of Toll-like Receptor 2 in Dental Primary Afferents Following Pulp Injury. toll样受体2在牙髓损伤后初级传入神经中的表达上调。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2021-10-31 DOI: 10.5607/en21018

Pa Reum Lee, Jin-Hee Lee, Ji Min Park, Seog Bae Oh

{"title":"Upregulation of Toll-like Receptor 2 in Dental Primary Afferents Following Pulp Injury.","authors":"Pa Reum Lee, Jin-Hee Lee, Ji Min Park, Seog Bae Oh","doi":"10.5607/en21018","DOIUrl":"https://doi.org/10.5607/en21018","url":null,"abstract":"Pulpitis (toothache) is a painful inflammation of the dental pulp and is a prevalent problem throughout the world. This pulpal inflammation occurs in the cells inside the dental pulp, which have host defense mechanisms to combat oral microorganisms invading the pulp space of exposed teeth. This innate immunity has been well studied, with a focus on Toll-like receptors (TLRs). The function of TLR4, activated by Gram-negative bacteria, has been demonstrated in trigeminal ganglion (TG) neurons for dental pain. Although Gram-positive bacteria predominate in the teeth of patients with caries and pulpitis, the role of TLR2, which is activated by Gram-positive bacteria, is poorly understood in dental primary afferent (DPA) neurons that densely innervate the dental pulp. Using Fura-2 based Ca2+ imaging, we observed reproducible intracellular Ca2+ responses induced by Pam3CSK4 and Pam2CSK4 (TLR2-specific agonists) in TG neurons of adult wild-type (WT) mice. The response was completely abolished in TLR2 knock-out (KO) mice. Single-cell RT-PCR detected Tlr2 mRNA in DPA neurons labeled with fluorescent retrograde tracers from the upper molars. Using the mouse pulpitis model, real-time RT-PCR revealed that Tlr2 and inflammatory-related molecules were upregulated in injured TG, compared to non-injured TG, from WT mice, but not from TLR2 KO mice. TLR2 protein expression was also upregulated in injured DPA neurons, and the change was corresponded with a significant increase in calcitonin gene-related peptide (CGRP) expression. Our results provide a better molecular understanding of pulpitis by revealing the potential contribution of TLR2 to pulpal inflammatory pain.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"30 5","pages":"329-340"},"PeriodicalIF":2.4,"publicationDate":"2021-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/42/16/en-30-5-329.PMC8572661.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39679957","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}

引用次数: 0

Altered Gene Expression Profiles in Neural Stem Cells Derived from Duchenne Muscular Dystrophy Patients with Intellectual Disability. 杜氏肌营养不良伴智力障碍患者神经干细胞基因表达谱的改变

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2021-08-31 DOI: 10.5607/en21008

Jahong Koo, Subin Park, Soo-Eun Sung, Jeehun Lee, Dae Soo Kim, Jungwoon Lee, Jae-Ran Lee, Nam-Soon Kim, Da Yong Lee

{"title":"Altered Gene Expression Profiles in Neural Stem Cells Derived from Duchenne Muscular Dystrophy Patients with Intellectual Disability.","authors":"Jahong Koo, Subin Park, Soo-Eun Sung, Jeehun Lee, Dae Soo Kim, Jungwoon Lee, Jae-Ran Lee, Nam-Soon Kim, Da Yong Lee","doi":"10.5607/en21008","DOIUrl":"https://doi.org/10.5607/en21008","url":null,"abstract":"Intellectual disability (ID) is a neurodevelopmental disorder defined by below-average intelligence (intelligence quotient of <70) accompanied by adaptive behavior deficits. Defects in the functions of neural stem cells during brain development are closely linked to the pathogenesis of ID. To understand the molecular etiology of ID, we examined neural stem cells from individuals with Duchenne muscular dystrophy (DMD), a genetic disorder in which approximately one-third of the patients exhibit ID. In this study, we generated induced pluripotent stem cells from peripheral blood mononuclear cells from a normal individual and DMD patients with and without ID to identify ID-specific functional and molecular abnormalities. We found defects in neural ectoderm formation in the group of DMD patients with ID. Our transcriptome analysis of patient-derived neural stem cells revealed altered expression of genes related to the hippo signaling pathway and neuroactive ligand-receptor interaction, implicating these in the pathogenesis of ID in patients with DMD.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"30 4","pages":"263-274"},"PeriodicalIF":2.4,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/28/b7/en-30-4-263.PMC8424384.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39384920","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}

引用次数: 0

Hyperoxygenation Treatment Reduces Beta-amyloid Deposition via MeCP2-dependent Upregulation of MMP-2 and MMP-9 in the Hippocampus of Tg-APP/PS1 Mice. 高氧处理通过mecp2依赖性上调Tg-APP/PS1小鼠海马中MMP-2和MMP-9来减少β -淀粉样蛋白沉积。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2021-08-31 DOI: 10.5607/en21014

Juli Choi, Hyejin Kwon, Pyung-Lim Han

{"title":"Hyperoxygenation Treatment Reduces Beta-amyloid Deposition via MeCP2-dependent Upregulation of MMP-2 and MMP-9 in the Hippocampus of Tg-APP/PS1 Mice.","authors":"Juli Choi, Hyejin Kwon, Pyung-Lim Han","doi":"10.5607/en21014","DOIUrl":"https://doi.org/10.5607/en21014","url":null,"abstract":"Recently we reported that hyperoxygenation treatment reduces amyloid-beta accumulation and rescues cognitive impairment in the Tg-APP/PS1 mouse model of Alzheimer's disease. In the present study, we continue to investigate the mechanism by which hyperoxygenation reduces amyloid-beta deposition in the brain. Hyperoxygenation treatment induces upregulation of matrix metalloproteinase-2 (MMP-2), MMP-9, and tissue plasminogen activator (tPA), the endopeptidases that can degrade amyloid-beta, in the hippocampus of Tg-APP/PS1 mice. The promoter regions of the three proteinase genes all contain potential binding sites for MeCP2 and Pea3, which are upregulated in the hippocampus after hyperoxygenation. Hyperoxygenation treatment in HT22 neuronal cells increases MeCP2 but not Pea3 expression. In HT22 cells, siRNA-mediated knockdown of Mecp2 decreases Mmp-9 expression and to a lesser extent, Mmp-2 and tPA expression. In mice, siRNA-mediated Mecp2 knockdown in the hippocampus reduces Mmp-9 expression, but not significantly Mmp-2 and tPA expression. The ChIP assay indicates that hyperoxygenation treatment in Tg-APP/PS1 mice increases MeCP2 binding to the promoter regions of Mmp-2 , Mmp-9 and tPA genes in the hippocampus. Together, these results suggest that hyperoxygenation increases the expression of MMP-2, MMP-9, and tPA, of which MMP-9 is upregulated via MeCP2 in neuronal cells, and MMP-2 and tPA are upregulated through MeCP2 and other nuclear factors.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"30 4","pages":"294-307"},"PeriodicalIF":2.4,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9e/a9/en-30-4-294.PMC8424382.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39385353","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}

引用次数: 5