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1.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781307

RESUMO

OBJECTIVE@#To analyze variants of PRRT2 gene in two children with paroxysmal kinesigenic dyskinesia.@*METHODS@#Genomic DNA of the two children and their parents was extracted from peripheral venous blood samples. All exons and their flanking regions of the PRRT2 gene were subjected to PCR and Sanger sequencing.@*RESULTS@#The two children were found to respectively harbor a c.282dupA and a c.715_716dupCC variant in exon 2 of the PRRT2 gene, which were both inherited from their mothers. Pooling together their frequencies in general population, genetic models, related literature and impact on protein function, the two novel variants were both predicted to be pathogenic.@*CONCLUSION@#The c.282dupA and c.715_716dupCC variants probably underlie the disease in the two children.


Assuntos
Criança , Distonia , Genética , Feminino , Humanos , Proteínas de Membrana , Genética , Mutação , Proteínas do Tecido Nervoso , Genética
2.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781302

RESUMO

OBJECTIVE@#To explore the genetic etiology of a pedigree affected with Norrie disease.@*METHODS@#Four individuals from the core family of the proband were subjected to whole exome sequencing in order to identify the pathological variant. Sanger sequencing was used to verify the finding among 7 additional members from the pedigree.@*RESULTS@#The proband and other 3 male patients have all carried a hemizygote c.361C>T (p.Arg121Trp) missense variant of the NDP gene, for which his mother, grandmother and two younger female cousins were heterozygous carriers. The same variant was not detected among unaffected males. Above results conformed to a X-linked recessive pattern of inheritance.@*CONCLUSION@#The missense variant c.361C>T of the NDP gene probably underlies the Norrie disease in this pedigree.


Assuntos
Cegueira , Genética , Proteínas do Olho , Genética , Feminino , Doenças Genéticas Ligadas ao Cromossomo X , Genética , Humanos , Masculino , Proteínas do Tecido Nervoso , Genética , Doenças do Sistema Nervoso , Genética , Linhagem , Degeneração Retiniana , Genética , Espasmos Infantis , Genética
3.
Acta Physiologica Sinica ; (6): 287-293, 2019.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-777187

RESUMO

This study was aimed to examine the expression and function of Slit/Robo family members in mouse ovary. Real-time PCR was used to assess the mRNA expression levels of Slit/Robo family members, and immunohistochemistry was used to examine the location of Slit2 and Robo1 in the ovary. The mRNA and protein expression levels of Slit2 and Robo1 in early-, middle- and late-phase corpus luteum (CL) were examined by real-time PCR and immunohistochemistry, respectively. Blocking agent ROBO1/Fc chimera was used in the luteal cells in vitro to examine the function of Slit/Robo signaling pathway in mouse CL. The results showed that, among the Slit/Robo family members, the expression levels of ligand Slit2 and receptor Robo1 were the highest in mouse ovarian tissue. Moreover, both of them were specifically expressed in mouse luteal cells. Compared with proestrus ovaries, the expression levels of Slit2 and Robo1 mRNA in the ovaries during diestrus were significantly up-regulated (P < 0.01, P < 0.001). The mRNA expression levels of Slit2 and Robo1 in late-phase CL were significantly increased when compared with pregnant CL. Furthermore, blocking Slit/Robo signaling pathway with ROBO1/Fc chimera in the luteal cells in vitro significantly decreased the apoptotic rate of late luteal cells. These results suggest that Slit/Robo family members are mainly expressed in the late-phase CL of ovary and participate in luteal cells apoptosis.


Assuntos
Animais , Apoptose , Feminino , Peptídeos e Proteínas de Sinalização Intercelular , Fisiologia , Células Lúteas , Biologia Celular , Camundongos , Proteínas do Tecido Nervoso , Fisiologia , Gravidez , Receptores Imunológicos , Fisiologia
4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776798

RESUMO

OBJECTIVE@#To explore clinical and genetic features of a pedigree affected with autosomal recessive neuromyotonia and axonal neuropathy (NMAN).@*METHODS@#For the proband and her parents, clinical data was collected, genomic DNA was extracted from peripheral blood samples. Triplet primed-PCR was carried out to detect dynamic mutation of DMPK and ZNF9 genes, which are responsible for myotonic dystrophy, by capillary electrophoresis. High-throughput sequencing was used to screen variants of candidate genes for Mendelian disorders involving the nervous system. Candidate variants were confirmed by Sanger sequencing. The genotype of the variant was determined in the parents and 100 healthy controls. Pathogenicity of the variant was assessed by ACMG criterion.@*RESULTS@#Mutation of DMPK and ZNF9 genes was excluded. DNA sequencing has identified a homozygous missense variant (c.335C>T, p.R119W) in the HINT1 gene. Both parents were found to carry the variant. The same variant was not found among the healthy controls. According to the ACMG criterion, the missense variant was classified as a pathogenic variant.@*CONCLUSION@#The c.335C>T (p.R119W) of the HINT1 gene probably underlie the disease in this pedigree. Above finding provided further evidence for the connection between HINT1 and NMAN and enriched the mutation spectrum of HINT1 gene.


Assuntos
Feminino , Genótipo , Homozigoto , Humanos , Síndrome de Isaacs , Genética , Proteínas do Tecido Nervoso , Genética , Linhagem
5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776771

RESUMO

OBJECTIVE@#To explore the genetic basis for a patient with autism.@*METHODS@#High-throughput sequencing was carried out to detect copy number variations in the patient.@*RESULTS@#DNA sequencing found that the patient has carried a 0.11 Mb deletion in distal 2p16.3 spanning from genomic position 50 820 001 to 50 922 000, which resulted removal of exon 6 and part of intron 7 of the NRXN1 gene. The same deletion was not found his parents and brother.@*CONCLUSION@#Partial deletion of the NRXN1 gene may underlie the disease in this patient.


Assuntos
Transtorno Autístico , Genética , Moléculas de Adesão Celular Neuronais , Genética , Variações do Número de Cópias de DNA , Deleção de Genes , Humanos , Masculino , Proteínas do Tecido Nervoso , Genética
6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776734

RESUMO

OBJECTIVE@#To explore the clinical features and molecular basis for a child featuring infantile epilepsy and developmental disorders.@*METHODS@#Clinical data and peripheral blood samples of the child and his parents were collected. The coding regions of genes associated with nervous system development were subjected to target region capture sequencing.@*RESULTS@#The child developed generalized spasm at 3 months and was diagnosed with epilepsy at 6 months of age. He was treated with Depakin but was diagnosed with mental retardation and developmental retardation at 3 years of age. A novel heterozygous c.3842T to G variant of the SYNE1 gene was detected. His father was found to carry the same variant and had a history of convulsions in infancy but with no mental or developmental anomalies.@*CONCLUSION@#A novel variant of SYNE1 gene was identified in this child, and the prognosis may be poor.


Assuntos
Pré-Escolar , Deficiências do Desenvolvimento , Genética , Epilepsia , Genética , Humanos , Lactente , Deficiência Intelectual , Genética , Masculino , Mutação , Proteínas do Tecido Nervoso , Genética , Proteínas Nucleares , Genética , Convulsões
7.
Chinese Acupuncture & Moxibustion ; (12): 1205-1210, 2019.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776187

RESUMO

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on the expressions of growth arrest-specific protein 7 (Gas7) and nerve growth factor (NGF) in arcuate nucleus (ARC) of rats with focal cerebral ischemia and explore the potential action mechanism of EA in treatment of focal cerebral ischemia.@*METHODS@#A total of 50 SD rats were randomized into 4 groups, named a normal group ( =12), a sham-operation group ( =12), a model group ( =14) and an EA group ( =12). In the model group and the EA group, the thread embolization method was adopted to duplicate the model of the right middle cerebral arterial embolism. In the sham-operation group, the skin of the neck was opened and sutured without any other intervention. In the EA group, EA was applied to "Baihui" (CV 20) and "Zusanli" (ST 36) on the left side, once a day, 30 min each time, consecutively for 21 days, while there was no any intervention in the normal group, the sham-operation group and the model group. Using the immunohistochemistry (IHC) method and Western blot method, the expressions of Gas7 and NFG of ARC on the ischemic side were determined. Using Nissle staining, the morphological changes in ARC neurons were observed.@*RESULTS@#The results of Nissle staining showed that there was no significant change in the morphology of ARC neurons in the normal group and the sham-operation group. In the model group, the volume of neuron cells was atrophied obviously and the cells were arranged irregularly. In the EA group, the morphology of ARC neuron was similar to the normal group. The results of IHC and Western blot indicated that the expressions of immunoreactive neurons and protein of Gas7 and NGF in ARC of the rats in the model group were increased obviously as compared with the normal group and the sham-operation group and the expressions in the EA group were further enhanced as compared with the model group (all <0.05).@*CONCLUSION@#Gas7 and NGF may be participated in the compensatory process of partial protection of the body in the patients with focal cerebral ischemia. EA up-regulates the expressions of Gas7 and NGF in ARC, which may be one of the neuroprotective mechanisms of EA in treatment of cerebral ischemia.


Assuntos
Animais , Isquemia Encefálica , Metabolismo , Terapêutica , Infarto Cerebral , Metabolismo , Terapêutica , Eletroacupuntura , Humanos , Fator de Crescimento Neural , Metabolismo , Proteínas do Tecido Nervoso , Metabolismo , Ratos , Ratos Sprague-Dawley
8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776028

RESUMO

Objective To explore the clinical characteristics of autoimmune disease with dual seropositive antibodies of leucine-rich glioma inactivated 1(LGI1)and contactin-associated protein 2(Caspr2).Methods The clinical data of seven patients with dual seropositive LGI1 and Caspr2 antibodies who were admitted to the Neurology Department of Peking Union Medical College Hospital from July 2014 to December 2017 were retrospectively analyzed.Results Central,peripheral and autonomic nervous systems were all involved in the seven cases;100%(7/7)presented with insomnia,myokymia,neuropahic pain and hyperhydrosis;71%(5/7)showed memory decline or psychiatric and behavioral symptoms;57%(4/7)had urinary hesitation or constipation;and 43%(3/7)had seizure.Electromyography showed 100%(6/6) of the patients had prolonged afterdischarges following normal M waves and/or abnormal spontaneous firing.Electroencephalography revealed slow waves or basic rhythm slowing in 71%(5/7)of patients.Electrocardiography showed sinus tachycardia,axis deviation,and prolonged QT intervals in 71%(5/7)of patients.One patient died from arrhythmia before immunotherapy.One died from pulmonary infection after immunotherapy.Improvement with immunotherapy was documented in the other five cases.No relapse was noted during the 1-2-year follow-up.Conclusions Autoimmune disease with dual seropositive antibodies of LGI1 and Caspr2 can diffusely affect the central,peripheral,and autonomic nervous systems.The possibility of this disease should be considered in patients with acute and subacute onset of neuropsychiatric symptoms,especially in patients with accompanying insomnia,myokymia,and hyperhydrosis.


Assuntos
Autoanticorpos , Sangue , Doenças Autoimunes , Alergia e Imunologia , Humanos , Proteínas de Membrana , Alergia e Imunologia , Proteínas do Tecido Nervoso , Alergia e Imunologia , Proteínas , Alergia e Imunologia , Estudos Retrospectivos
9.
Neuroscience Bulletin ; (6): 497-506, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-775419

RESUMO

Neuroligins (NLs) are postsynaptic cell-adhesion proteins that play important roles in synapse formation and the excitatory-inhibitory balance. They have been associated with autism in both human genetic and animal model studies, and affect synaptic connections and synaptic plasticity in several brain regions. Yet current research mainly focuses on pyramidal neurons, while the function of NLs in interneurons remains to be understood. To explore the functional difference among NLs in the subtype-specific synapse formation of both pyramidal neurons and interneurons, we performed viral-mediated shRNA knockdown of NLs in cultured rat cortical neurons and examined the synapses in the two major types of neurons. Our results showed that in both types of neurons, NL1 and NL3 were involved in excitatory synapse formation, and NL2 in GABAergic synapse formation. Interestingly, NL1 affected GABAergic synapse formation more specifically than NL3, and NL2 affected excitatory synapse density preferentially in pyramidal neurons. In summary, our results demonstrated that different NLs play distinct roles in regulating the development and balance of excitatory and inhibitory synapses in pyramidal neurons and interneurons.


Assuntos
Animais , Moléculas de Adesão Celular Neuronais , Fisiologia , Células Cultivadas , Córtex Cerebral , Embriologia , Fisiologia , Neurônios GABAérgicos , Fisiologia , Interneurônios , Fisiologia , Proteínas de Membrana , Fisiologia , Proteínas do Tecido Nervoso , Fisiologia , Isoformas de Proteínas , Fisiologia , Células Piramidais , Fisiologia , Ratos Sprague-Dawley , Sinapses , Fisiologia
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-781260

RESUMO

OBJECTIVE@#To investigate the regulatory role of Musashi-1 (MSI1) in the proliferation and growth of hepatocellular carcinoma (HCC) cells.@*METHODS@#We examined the expression of MSI1 in HCC and paired adjacent tissues from 24 patients using immunohistochemistry and Western blotting. A MSI1-expressing vector was constructed and stably transfected into HepG2 cells, and short hairpin RNAs (shRNAs) that targeted MSI1 mRNA were ligated into the vector and stably transfected in Huh7 cells. The effects of MSI1 overexpression and silencing on the proliferation, viability and cell cycle of HepG2 cells were investigated using flow cytometry or MTT assay. The expressions of PCNA, cyclin D1, APC and β-catenin in the HCC cells were detected with Western blotting.@*RESULTS@#MSI1 expression was significantly up-regulated in HCC tissues as compared with that in the adjacent tissues. Overexpression of MSI1 in HepG2 cells resulted in significantly enhanced cell growth ( < 0.01) and significantly reduced G0/G1 phase cells from (58.42±3.18)% to (40.67±1.22)% and increased S phase cells from (28.51± 1.93)% to (40.06±1.92)% ( < 0.01), causing also increases in the expressions of PCNA and Cyclin D1. Knockdown of MSI1 in Huh7 cells obviously inhibited the cell growth and caused cell cycle arrest at the G1/S phase ( < 0.01) with reduced protein expressions of PCNA and cyclin D1. Overexpression of MSI1 in HepG2 cells also down-regulated the expression of APC and up-regulated the expression of β-catenin protein, while MSI1 knockdown caused reverse changes in Huh7 cells.@*CONCLUSIONS@#MSI1 promotes the progression of HCC through positive modulation of cell growth and cell cycle the Wnt/β-catenin pathway.


Assuntos
Carcinoma Hepatocelular , Ciclo Celular , Proliferação de Células , Células Hep G2 , Humanos , Neoplasias Hepáticas , Proteínas do Tecido Nervoso , Metabolismo , Proteínas de Ligação a RNA , Metabolismo
11.
Journal of Experimental Hematology ; (6): 1001-1007, 2019.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771848

RESUMO

OBJECTIVE@#To investigate the methylation status of CHD5 gene promoter in bone marrow from acute myeloid leukemia (AML) patients, and the underlying mechanism for initiating the pathogenesis of AML via p19/p53/p21 pathway.@*METHODS@#Methylation status of the CHD5 gene promoter was detected by using methylation-specific polymerase chain reaction (MSPCR) in bone marrow from AML patients, and the iron-deficiency anemia (IDA) samples were served as control. The expression of CHD5, p19, p53 and p21 was determined by real-time quantitative reverse transcriptase PCR and Western blot.@*RESULTS@#The methylation of CHD5 gene in bone marrow from AML patients increased significantly (39.06%) as compared with control group (6.67%). The methylation of CHD5 gene significantly correlated with chromosome karyotype differentiation (P<0.01), but did not correlate with the patient's sex, age and clinical classification (P>0.05). The mRNA expression of CHD5 gene in AML decreased, compared with control group, the mRNA and protein expression of p19, p53 and p21 in AML with CHD5 methylation promoter decreased.@*CONCLUSION@#The hypermeltylation of CHD5 gene promoter in AML patients can lead to decrease of CHD5, p19, p53 and p21 expression levels which may reduce the inhibitory effect on proliferation of leukemia cells through the regulation of p19, p53 and p21 pathway, thus promotes the occurence of AML.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina , Inibidor de Quinase Dependente de Ciclina p21 , DNA Helicases , Metilação de DNA , Humanos , Leucemia Mieloide Aguda , Proteínas do Tecido Nervoso , Regiões Promotoras Genéticas , Proteína Supressora de Tumor p53
12.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-773419

RESUMO

OBJECTIVE@#Pyroptosis is an inflammatory form of programmed cell death. This phenomenon has been recently reported to play an important role in radiation-induced normal tissue injury. Connexin43 (Cx43) is a gap junction protein that regulates cell growth and apoptosis. In this study, we investigated the effect of Cx43 on X-ray-induced pyroptosis in the human umbilical vein endothelial cells (HUVECs).@*METHODS@#HUVECs, Cx43 overexpression, and Cx43 knockdown strains were irradiated with 10 Gy. Proteins were detected using western blot analysis. Cell pyroptosis was evaluated using the fluorescence-labeled inhibitor of caspase assay (FLICA) and propidium iodide staining through flow cytometry and confocal microscopy. Cell morphology and cytotoxicity were detected by scanning electron microscopy and lactate dehydrogenase release assay, respectively.@*RESULTS@#Irradiation with 10 Gy X-ray induced pyroptosis in the HUVECs and reduced Cx43 expression. The pyroptosis in the HUVECs was significantly attenuated by overexpression of Cx43 as it decreased the level of active caspase-1. However, interference of Cx43 expression with siRNA significantly promoted pyroptosis by increasing the active caspase-1 level. Pannexin1 (Panx1), a gap junction protein regulates pyroptosis, and its cleaved form is used to evaluate channel opening and active state. The level of cleaved Panx1 in the HUVECs and Cx43 knockdown strains increased in the presence of X-ray, but decreased in the Cx43 overexpression strains. Furthermore, interference of Panx1 with siRNA alleviated the upregulation of pyroptosis caused by Cx43 knockdown.@*CONCLUSION@#Results suggest that single high-dose X-ray irradiation induces pyroptosis in the HUVECs. In addition, Cx43 regulates pyroptosis directly by activating caspase-1 or indirectly by cleaving Panx1.


Assuntos
Caspase 1 , Genética , Metabolismo , Conexina 43 , Genética , Metabolismo , Conexinas , Genética , Metabolismo , Regulação da Expressão Gênica , Efeitos da Radiação , Células Endoteliais da Veia Umbilical Humana , Fisiologia , Efeitos da Radiação , Humanos , Proteínas do Tecido Nervoso , Genética , Metabolismo , Piroptose , Raios X
13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-772120

RESUMO

OBJECTIVE@#To investigate the molecular genetic mechanism of Charcot- Marie-Tooth (CMT) disease in a pedigree.@*METHODS@#Genomic DNA was extracted from the peripheral blood of the family members of a pedigree with autosomal dominant CMT disease, and 65 candidate genes of the proband were screened using target exon capture and the next generation sequencing, and the suspicious genes were verified using Sanger sequencing. PolyPhen-2, PROVEAN and SIFT software were used to predict the function of the mutant genes, and PyMOL-1 software was used to simulate the mutant protein structure.@*RESULTS@#A heterozygous missense mutation [c.371A>G (p.Y124C)] was detected in exon 3 of gene of the proband. This heterozygous mutation was also detected in both the proband's mother and her brother, but not in her father. Multiple sequence alignment analysis showed that tyrosine at codon 124 of GDAP1 protein was highly conserved. All the 3 prediction software predicted that the mutation was harmful. Molecular structure simulation showed a weakened interaction force between the amino acid residues at codon 124 and the surrounding amino acid residues to affect the overall stability of the protein.@*CONCLUSIONS@#The mutation of gene may be related to the pathogenesis of autosomal dominant AD-CMT in this pedigree. The newly discovered c.371A>G mutation (p.Y124C) expands the mutation spectrum of gene, but further study is needed to clarify the underlying pathogenesis.


Assuntos
Aminoácidos , Doença de Charcot-Marie-Tooth , Genética , Feminino , Genes Dominantes , Genética , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Métodos , Humanos , Masculino , Mutação de Sentido Incorreto , Proteínas do Tecido Nervoso , Genética , Linhagem , Software
14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-772051

RESUMO

OBJECTIVE@#To investigate the effect of blocking pannexin-1 against acute kidney injury induced by cisplatin.@*METHODS@#Twenty-six male C57BL/6 mice aged 6-8 weeks were randomly divided into control group, cisplatin model (Cis) group and cisplatin + carbenoxolone treatment group (Cis + CBX). In Cis group and Cis + CBX group, the mice were injected intraperitoneally with 20 mg/kg of cisplatin and with CBX (20 mg/kg) at 30 min before and 24 and 48 h after cisplatin inhjection, respectively. All the mice were sacrificed at 72 h after cisplatin injection, and plasma and kidney samples were collected for testing mRNA and protein expression levels of pannexin-1 in the renal tissue using RT-qPCR and Western blotting and for detecting plasma creatinine and BUN levels; the pathological changes in the renal tissues were observed using Periodic Acid-Schiff staining. The expression of kidney injury molecule 1 (KIM-1) was examined using immunohistochemistry and the mRNA expressions of KIM-1 and neutrophil gelatinase- related lipid transport protein (NGAL) were detected by RT-qPCR to evaluate the injuries of the renal tubules. The infiltration of F4/80-positive macrophages and CD4-positive T cells were observed by immunofluorescence. In the experiment, human proximal tubule epithelial cell line HK-2 was stimulated with 50 μmol/L cisplatin to establish a cell model of acute kidney injury, and the mRNA and protein expressions of pannexin-1 were detected by RT-qPCR and Western blotting at 4, 6, 12, 18 and 24 h after the stimulation.@*RESULTS@#Compared with the control mice, the cisplatin-treated mice showed significantly up-regulated protein levels ( < 0.05) and mRNA levels ( < 0.005) of pannexin-1 in the kidney tissue. Cisplatin stimulation also caused significant increases in the protein levels ( < 0.005) and mRNA levels ( < 0.005) of pannexin-1 in cultured HK-2 cells. Compared with cisplatin-treated mice, the mice treated with both cisplatin and the pannexin-1 inhibitor CBX showed obviously lessened kidney pathologies and milder renal tubular injuries with significantly reduced plasma BUN and Scr levels ( < 0.01), expressions of KIM-1 and NGAL in the kidney ( < 0.05), and infiltration of F4/80-positive macrophages ( < 0.01) and CD4- positive T cells ( < 0.05) in the kidney tissues.@*CONCLUSIONS@#In cisplatin induced acute kidney injury mice model, Pannexin-1 expression is up-regulated in the kidneys tissue, and blocking pannexin-1 alleviates the acute kidney injury reducing renal inflammatory cell infiltration.


Assuntos
Lesão Renal Aguda , Tratamento Farmacológico , Metabolismo , Animais , Cisplatino , Farmacologia , Conexinas , Metabolismo , Reagentes para Ligações Cruzadas , Farmacologia , Humanos , Rim , Túbulos Renais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso , Metabolismo , Distribuição Aleatória
15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771990

RESUMO

OBJECTIVE@#To detect mutation of NDP gene in a pedigree affected with Norrie disease.@*METHODS@#Sanger sequencing was used to analyze the NDP gene at Xp11.3. Prenatal diagnosis was performed on amniotic fluid sample after the causative gene was detected.@*RESULTS@#Sanger sequencing has revealed a c.2T>C (p.M1T) missense mutation of the NDP gene in the proband and the fetus. The same variation was not found in ClinVar and HGMD database.@*CONCLUSION@#The c.2T>C mutation of the NDP gene probably underlies the Norrie disease in this pedigree.


Assuntos
Cegueira , Proteínas do Olho , Feminino , Doenças Genéticas Ligadas ao Cromossomo X , Humanos , Proteínas do Tecido Nervoso , Doenças do Sistema Nervoso , Linhagem , Gravidez , Diagnóstico Pré-Natal , Degeneração Retiniana , Espasmos Infantis
16.
Neuroscience Bulletin ; (6): 64-73, 2018.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-777070

RESUMO

Tetanic stimulation of the sciatic nerve (TSS) triggers long-term potentiation in the dorsal horn of the spinal cord and long-lasting pain hypersensitivity. CX3CL1-CX3CR1 signaling is an important pathway in neuronal-microglial activation. Nuclear factor κB (NF-κB) is a key signal transduction molecule that regulates neuroinflammation and neuropathic pain. Here, we set out to determine whether and how NF-κB and CX3CR1 are involved in the mechanism underlying the pathological changes induced by TSS. After unilateral TSS, significant bilateral mechanical allodynia was induced, as assessed by the von Frey test. The expression of phosphorylated NF-κB (pNF-κB) and CX3CR1 was significantly up-regulated in the bilateral dorsal horn. Immunofluorescence staining demonstrated that pNF-κB and NeuN co-existed, implying that the NF-κB pathway is predominantly activated in neurons following TSS. Administration of either the NF-κB inhibitor ammonium pyrrolidine dithiocarbamate or a CX3CR1-neutralizing antibody blocked the development and maintenance of neuropathic pain. In addition, blockade of NF-κB down-regulated the expression of CX3CL1-CX3CR1 signaling, and conversely the CX3CR1-neutralizing antibody also down-regulated pNF-κB. These findings suggest an involvement of NF-κB and the CX3CR1 signaling network in the development and maintenance of TSS-induced mechanical allodynia. Our work suggests the potential clinical application of NF-κB inhibitors or CX3CR1-neutralizing antibodies in treating pathological pain.


Assuntos
Animais , Anticorpos , Antioxidantes , Receptor 1 de Quimiocina CX3C , Alergia e Imunologia , Metabolismo , Citocinas , Metabolismo , Modelos Animais de Doenças , Inibidores Enzimáticos , Gânglios Espinais , Metabolismo , Hiperalgesia , Metabolismo , Proteínas do Tecido Nervoso , Metabolismo , Limiar da Dor , Fisiologia , Estimulação Física , Prolina , Ratos , Ratos Sprague-Dawley , Nervo Isquiático , Fisiologia , Transdução de Sinais , Fisiologia , Medula Espinal , Metabolismo , Tiocarbamatos , Regulação para Cima , Fisiologia
17.
Neuroscience Bulletin ; (6): 419-437, 2018.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-777045

RESUMO

A previous study has indicated that Krüppel-like factor 7 (KLF7), a transcription factor that stimulates Schwann cell (SC) proliferation and axonal regeneration after peripheral nerve injury, is a promising therapeutic transcription factor in nerve injury. We aimed to identify whether inhibition of microRNA-146b (miR-146b) affected SC proliferation, migration, and myelinated axon regeneration following sciatic nerve injury by regulating its direct target KLF7. SCs were transfected with miRNA lentivirus, miRNA inhibitor lentivirus, or KLF7 siRNA lentivirus in vitro. The expression of miR146b and KLF7, as well as SC proliferation and migration, were subsequently evaluated. In vivo, an acellular nerve allograft (ANA) followed by injection of GFP control vector or a lentiviral vector encoding an miR-146b inhibitor was used to assess the repair potential in a model of sciatic nerve gap. miR-146b directly targeted KLF7 by binding to the 3'-UTR, suppressing KLF7. Up-regulation of miR-146b and KLF7 knockdown significantly reduced the proliferation and migration of SCs, whereas silencing miR-146b resulted in increased proliferation and migration. KLF7 protein was localized in SCs in which miR-146b was expressed in vivo. Similarly, 4 weeks after the ANA, anti-miR-146b increased KLF7 and its target gene nerve growth factor cascade, promoting axonal outgrowth. Closer analysis revealed improved nerve conduction and sciatic function index score, and enhanced expression of neurofilaments, P0 (anti-peripheral myelin), and myelinated axon regeneration. Our findings provide new insight into the regulation of KLF7 by miR-146b during peripheral nerve regeneration and suggest a potential therapeutic strategy for peripheral nerve injury.


Assuntos
Animais , Movimento Celular , Genética , Proliferação de Células , Genética , Modelos Animais de Doenças , Feminino , Gânglios Espinais , Biologia Celular , Regulação da Expressão Gênica , Genética , Fisiologia , Células HEK293 , Humanos , Fatores de Transcrição Kruppel-Like , Genética , Metabolismo , Masculino , MicroRNAs , Genética , Metabolismo , Placa Motora , Genética , Proteína P0 da Mielina , Metabolismo , Regeneração Nervosa , Genética , Fisiologia , Proteínas do Tecido Nervoso , Metabolismo , RNA Interferente Pequeno , Genética , Metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Neuropatia Ciática , Metabolismo , Cirurgia Geral , Terapêutica
18.
Neuroscience Bulletin ; (6): 247-260, 2018.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-777042

RESUMO

The differentiation and maturation of oligodendrocyte precursor cells (OPCs) is essential for myelination and remyelination in the CNS. The failure of OPCs to achieve terminal differentiation in demyelinating lesions often results in unsuccessful remyelination in a variety of human demyelinating diseases. However, the molecular mechanisms controlling OPC differentiation under pathological conditions remain largely unknown. Myt1L (myelin transcription factor 1-like), mainly expressed in neurons, has been associated with intellectual disability, schizophrenia, and depression. In the present study, we found that Myt1L was expressed in oligodendrocyte lineage cells during myelination and remyelination. The expression level of Myt1L in neuron/glia antigen 2-positive (NG2) OPCs was significantly higher than that in mature CC1 oligodendrocytes. In primary cultured OPCs, overexpression of Myt1L promoted, while knockdown inhibited OPC differentiation. Moreover, Myt1L was potently involved in promoting remyelination after lysolecithin-induced demyelination in vivo. ChIP assays showed that Myt1L bound to the promoter of Olig1 and transcriptionally regulated Olig1 expression. Taken together, our findings demonstrate that Myt1L is an essential regulator of OPC differentiation, thereby supporting Myt1L as a potential therapeutic target for demyelinating diseases.


Assuntos
Animais , Diferenciação Celular , Fisiologia , Doenças Desmielinizantes , Lisofosfatidilcolinas , Toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso , Metabolismo , Células Precursoras de Oligodendrócitos , Biologia Celular , Metabolismo , Oligodendroglia , Biologia Celular , Metabolismo , Remielinização , Fisiologia , Fatores de Transcrição , Metabolismo
19.
Neuroscience Bulletin ; (6): 465-475, 2018.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-777041

RESUMO

The visual system plays an important role in our daily life. In this study, we found that loss of dendritic cell factor 1 (DCF1) in the primary visual cortex (V1) caused a sight deficit in mice and induced an abnormal increase in glutamic acid decarboxylase 67, an enzyme that catalyzes the decarboxylation of glutamate to gamma aminobutyric acid and CO, particularly in layer 5. In vivo electrophysiological recordings confirmed a decrease in delta, theta, and beta oscillation power in DCF1-knockout mice. This study presents a previously unknown function of DCF1 in V1, suggests an unknown contact between DCF1 and GABA systems, and provides insight into the mechanism and treatment of visual deficits.


Assuntos
Animais , Ondas Encefálicas , Genética , Modelos Animais de Doenças , Eletroencefalografia , Regulação da Expressão Gênica , Genética , Corpos Geniculados , Metabolismo , Ginkgolídeos , Glutamato Descarboxilase , Metabolismo , Lactonas , Proteínas de Membrana , Genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso , Genética , Estimulação Luminosa , Proteínas Proto-Oncogênicas c-fos , Metabolismo , Transtornos da Visão , Tratamento Farmacológico , Genética , Patologia , Córtex Visual , Metabolismo , Patologia , Ácido gama-Aminobutírico , Metabolismo
20.
Neuroscience Bulletin ; (6): 769-778, 2018.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-777025

RESUMO

Previous genetic fate-mapping studies have indicated that embryonic glial fibrillary acidic protein-positive (GFAP) cells are multifunctional progenitor/neural stem cells that can produce astrocytes as well as neurons and oligodendrocytes throughout the adult mouse central nervous system (CNS). However, emerging evidence from recent studies indicates that GFAP cells adopt different cell fates and generate different cell types in different regions. Moreover, the fate of GFAP cells in the young adult mouse CNS is not well understood. In the present study, hGFAP-Cre/R26R transgenic mice were used to investigate the lineage of embryonic GFAP cells in the young adult mouse CNS. At postnatal day 21, we found that GFAP cells mainly generated NeuN neurons in the cerebral cortex (both ventral and dorsal), hippocampus, and cerebellum. Strangely, these cells were negative for the Purkinje cell marker calbindin in the cerebellum and the neuronal marker NeuN in the thalamus. Thus, contrary to previous studies, our genetic fate-mapping revealed that the cell fate of embryonic GFAP cells at the young adult stage is significantly different from that at the adult stage.


Assuntos
Animais , Astrócitos , Biologia Celular , Metabolismo , Encéfalo , Biologia Celular , Metabolismo , Calbindinas , Metabolismo , Proteína Glial Fibrilar Ácida , Metabolismo , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso , Metabolismo , Células-Tronco Neurais , Biologia Celular , Metabolismo , Neurônios , Biologia Celular , Metabolismo , Proteínas Nucleares , Metabolismo
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