RESUMO
OBJECTIVES: To describe the physical growth of healthy children under 7 years in China based on the latest national survey and provide more data for revising growth reference and monitoring the impact of social development on children's health and growth. METHODS: In the cross-sectional survey, 161,774 healthy children under 7 years were selected by multistage stratified cluster sampling method in nine cities of China. According to the geographical location, the nine cities were divided into northern, central and southern regions, and each city included urban and suburban areas. Anthropometric measurements were obtained on the spots and other related information was collected with questionnaires. RESULTS: There were slight urban-suburban difference and obvious regional difference in anthropometric measurements in China. Comparison with the 4th NSPGDC in 2005, measurements increased 0.1-1.1 kg in weight, 0.5-1.8 cm in height in urban areas (except children under 3 years) and 0.1-2.5 kg in weight, 0.2-3.8 cm in height in suburban areas. The urban-suburban difference of those measurements became smaller than 10 years ago, but their regional difference persistently exist. Chinese children were 0.36 SD in weight, 0.43 SD in height in urban areas and 0.30 SD in weight, 0.30 SD in height in suburban areas higher than WHO standards. CONCLUSIONS: Physical growth of children under 7 years old was undergoing a slowly positive secular trend during the latest decade in more economically developed regions of China. Urban-suburban difference of those measurements became smaller, while their regional difference persistently exist. Chinese healthy children under 7 years in nine cities was taller and heavier than WHO standards.
Assuntos
Estatura/fisiologia , Peso Corporal/fisiologia , Desenvolvimento Infantil/fisiologia , Gráficos de Crescimento , População Urbana/estatística & dados numéricos , Criança , Pré-Escolar , Estudos Transversais , Escolaridade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Valores de ReferênciaRESUMO
Our previous studies found that Homer 1a, a scaffolding protein localized at the post-synaptic density (PSD) of glutamatergic excitatory synapses, is significantly down-regulated in the brain of spontaneous hypertensive rats (SHR), an animal model of attention deficit hyperactivity disorder (ADHD). Furthermore, a first-line treatment drug for ADHD, methylphenidate, can up-regulate the expression of Homer 1a. To investigate the possible role of Homer 1a in the etiology and pathogenesis of ADHD, a lentiviral vector containing miRNA specific for Homer 1a was constructed in this study. Intracerebroventricular injection of this vector into the brain of Sprague Dawley (SD) rats significantly decreased Homer 1a mRNA and protein expression levels. Compared to their negative controls, these rats displayed a range of abnormal behaviors, including increased locomotor activity and non-selective attention and impaired learning ability. Our results indicated that Homer 1a down-regulation results in deficits in control over behavioral output and learning similar to ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Encéfalo , Proteínas de Transporte , Atividade Motora/genética , Animais , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Comportamento Animal , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Vetores Genéticos , Proteínas de Arcabouço Homer , Humanos , Injeções Intraventriculares , Lentivirus , Metilfenidato/administração & dosagem , Interferência de RNA , RatosRESUMO
As one kind of novel noncoding RNA, circular RNAs (circRNAs) are involved in different biological processes. Although growing evidences have supported the important role of circRNAs in renal diseases, the mechanism remains unclear in neonatal acute kidney injury (AKI). High-throughput sequencing analysis was used to investigate the expression of circRNAs between hypoxia-induced AKI neonates and controls. Bioinformatics analysis was conducted to predict the function of differentially expressed circRNAs. Finally, the differentially expressed circRNAs were screened and determined by quantitative real-time PCR (qPCR). (1) A total of 296 differentially expressed circRNAs were identified (Fold change >2 and p < 0.05). Of them, 184 circRNAs were markedly upregulated, and 112 were significantly downregulated in the AKI group. (2) The pathway analysis showed that ubiquitin-mediated proteolysis, renal cell carcinoma, Jak-STAT, and HIF-1 signaling pathways participated in AKI. (3) Top five upregulated and five downregulated circRNAs with higher fold changes were selected for qPCR validation. Hsa_circ_0008898 (Fold Change = 5.48, p = 0.0376) and hsa_circ_0005519 (Fold Change = 4.65, p = 0.0071) were significantly upregulated, while hsa_circ_0132279 (Fold Change = -4.47, p = 0.0008), hsa_circ_0112327 (Fold Change = -4.26, p = 0.0048), and hsa_circ_0017647 (Fold Change = -4.15, p = 0.0313) were significantly downregulated in asphyxia-induced AKI group compared with the control group. This study could contribute to future research on neonatal AKI and facilitate the identification of novel therapeutic targets.
Assuntos
Injúria Renal Aguda , MicroRNAs , Recém-Nascido , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Análise de Sequência de RNA , Injúria Renal Aguda/genética , Biologia Computacional , Sequência de Bases , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
OBJECTIVE: To evaluate the association between pulmonary hemorrhage and bronchopulmonary dysplasia (BPD) in very low birth weight infants (VLBWIs). METHODS: The study participants were all VLBW newborns admitted from January 1, 2019 to December 31, 2021. The BPD subjects finally included were VLBWIs who survived until the diagnosis was established. This study was divided into pulmonary hemorrhage group (PH group, n = 35) and non-pulmonary hemorrhage group (Non-PH group, n = 190). RESULTS: By univariate analysis it was found that premature rupture of membranes, tracheal intubation in the delivery room, duration of mechanical ventilation, course of invasive ventilation (≥3 courses), pulmonary surfactant (>1 dose), medically and surgically treated patent ductus arteriosus, grade III-IV RDS, early onset sepsis, BPD and moderate to severe BPD showed significant differences between groups (p < .05). By Multivariate analysis, pulmonary hemorrhage did not increase the risks of BPD and moderate to severe BPD (adjusted OR for BPD = 1.710, 95% CI 0.581-5.039; adjusted OR for moderate to severe BPD = 2.401, 95% CI 0.736-7.834). CONCLUSION: It suggests that pulmonary hemorrhage is not associated with the development of BPD and moderate to severe BPD in VLBWIs.
Assuntos
Displasia Broncopulmonar , Permeabilidade do Canal Arterial , Lactente , Feminino , Recém-Nascido , Humanos , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/epidemiologia , Recém-Nascido de muito Baixo Peso , Peso ao Nascer , Respiração Artificial , Permeabilidade do Canal Arterial/complicações , Idade GestacionalRESUMO
NYGGF4, an obesity-related gene, is proposed to be involved in the development of insulin resistance. Skeletal muscle is a primary target organ for insulin and NYGGF4 showed a relatively high expression level in skeletal muscle. Therefore, this study aimed to explore the effect of NYGGF4 on insulin sensitivity of skeletal muscle cells. RNA interference (RNAi) was adopted to silence NYGGF4 expression in mice C2C12 skeletal myocytes. A remarkably increased insulin-stimulated glucose uptake and GLUT4 translocation was observed in NYGGF4 silencing C2C12 cells. Importantly, the enhanced glucose uptake induced by NYGGF4 silencing could be abrogated by the PI3K inhibitor LY294002. In addition, the crucial molecules involved in PI3K insulin signaling pathway were detected by western blotting. The results showed that NYGGF4 knockdown dramatically activate the insulin-stimulated phosphorylation of IRS-1 and AKT. Taken together, these data demonstrate that NYGGF4 knockdown increases glucose transport in myocytes by activation of the IRS-1/PI3K/AKT insulin pathway.
Assuntos
Proteínas de Transporte/metabolismo , Glucose/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Proteínas de Transporte/genética , Técnicas de Cultura de Células , Diferenciação Celular/fisiologia , Técnicas de Silenciamento de Genes , Insulina/metabolismo , Camundongos , Fibras Musculares Esqueléticas/citologia , Mioblastos/metabolismo , Transdução de Sinais , TransfecçãoRESUMO
Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that affect embryonic development. The purpose of this study was to examine the effects of embryonic exposure to PCBs on early retinal development in zebrafish, Danio rerio. Zebrafish embryos were immediately exposed to different concentrations (0, 0.125, 0.25, 0.5, 1.0 and 2.0 mg) of PCBs per liter of medium at 28.5 °C. Embryos were assessed at 30, 48, 72 and 96 h post-fertilization (hpf) for changes in embryonic survival rate, development, larval retinal morphology and ultrastructure of the retina. The results show that PCB exposure decreased the survival rate of embryos in a time- and dose-dependent manner. Embryos exposed to the higher concentrations of PCBs (0.5, 1.0 and 2.0 mg l(-1) ) displayed obvious gross morphological deformities. At 72 hpf, the retinal layer development of zebrafish was delayed at higher PCB concentrations (1.0 mg l(-1) ). At 96 hpf, irregularity of photoreceptor cells arrangement and thickening of photoreceptor and ganglionic layers were observed in PCB-treated larvae at concentrations of 0.25-1 mg l(-1) . Ultrastructural examination showed signs of growth inhibition of the photoreceptor outer segment at 0.25-1 mg l(-1) PCB exposure at 72 hpf, as well as the appearance of massive vacuoles and holes inside the outer segments in the PCB exposure group at 96 hpf. These results suggest that embryonic exposure to moderate and high levels of PCBs induced developmental deficits in zebrafish retinas, particularly in photoreceptor cells.
Assuntos
Anormalidades Induzidas por Medicamentos , Bifenilos Policlorados/toxicidade , Retina/anormalidades , Peixe-Zebra/embriologia , Animais , Relação Dose-Resposta a Droga , Retina/patologia , Retina/ultraestruturaRESUMO
NYGGF4, an obesity-related gene, is proposed to be involved in the development of insulin resistance; however, the underlying molecular mechanisms remain unclear. In the present analysis, NimbleGen tiling arrays were used to determine the patterns of genomic DNA methylation at CpG islands and promoters in NYGGF4-overexpression adipocytes. A total of 2352 CpG dinucleotides in 2018 genes and 3490 CpG dinucleotides in 3064 genes were found to be hypermethylated or hypomethylated, respectively, in NYGGF4-overexpression adipocytes. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis revealed enrichment of biological processes associated with energy metabolism and signal transduction events, including the peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathway, and mitogen-activated protein kinases(MAPK) and Ras homolog gene family, member A (RhoA) signaling. These data demonstrate that differentially methylated genes are significantly overrepresented in NYGGF4-overexpression adipocytes, providing valuable clues for further exploration of the role of NYGGF4 in insulin sensitivity regulation.
Assuntos
Adipócitos/metabolismo , Proteínas de Transporte/biossíntese , Metilação de DNA/fisiologia , Regulação da Expressão Gênica/fisiologia , Genoma/fisiologia , Resistência à Insulina/fisiologia , Células 3T3-L1 , Adipócitos/citologia , Animais , Ilhas de CpG/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , PPAR gama/metabolismo , Regiões Promotoras Genéticas/fisiologia , Proteínas rho de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTPRESUMO
Diabetes is a global public health problem. Maintaining optimal glycemic control is critical for minimizing associated long-term complications and achieving better quality of life. Effective diabetes self-management education is one key component to enhance diabetes clients' self-management capabilities. The research team established a "Caring for Yourself-Managing Your Diabetes" Web site, which contained 35 video clips about diabetes management. The aim of this study was to evaluate user satisfaction with the Web-based diabetes self-management education program. A convenience sample of 100 diabetes clients (mean age, 61.5 [SD, 10.7] years) was invited to view one of the video clips via a laptop computer. A modified version of the Computer-Aided Learning Evaluation Questionnaire and the End-User Computing Satisfaction Questionnaire was used to evaluate participants' satisfaction with the program. The results indicate that participants were satisfied with the format, content, and accuracy of the Web-based diabetes education program. Some participants suggested adding different types of exercises that are specific to the needs of client groups and more explanation of diabetes medications. The results of this study support the use of computer-assisted learning as a promising method for delivering diabetes self-management education, which is satisfactory to diabetes clients.
Assuntos
Instrução por Computador , Diabetes Mellitus/terapia , Internet , Educação de Pacientes como Assunto/métodos , Satisfação do Paciente/estatística & dados numéricos , Autocuidado , Idoso , Estudos Transversais , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de SaúdeRESUMO
OBJECTIVE: To study the growth rhythm of preterm appropriate for gestational age (AGA) infants by investigating their physical catch-up growth characteristics. METHODS: Eighty-four preterm AGA newborns (44 males and 40 females) with gestational ages between 28-36 weeks were enrolled. The weight, length and head circumference were evaluated by Z score according to the criterions of actual and corrected ages. RESULTS: The preterm infants had the catch-up growth in weight, length and head circumference in the first year of life. The growth velocity within the first three months was the highest. The velocity in the weight catch-up was higher than that in the length. CONCLUSIONS: The fastest growing period is the early three month of life in preterm AGA infants. The catch-up growth in weight and length is unbalanced.
Assuntos
Recém-Nascido Prematuro/crescimento & desenvolvimento , Estatura , Peso Corporal , Feminino , Idade Gestacional , Cabeça/crescimento & desenvolvimento , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , MasculinoRESUMO
NYGGF4 is a recently discovered gene that is involved in obesity-associated insulin resistance. It has been suggested that mitochondrial dysfunction might be responsible for the development of insulin resistance induced by NYGGF4 overexpression. In the present study, we aimed to define the impact of down-regulating NYGGF4 expression by RNA interference (RNAi) on the insulin sensitivity and mitochondrial function of 3T3-L1 adipocytes. The results revealed that NYGGF4 knockdown enhanced the glucose uptake of adipocytes, which reconfirmed the regulatory function of NYGGF4 in adipocyte insulin sensitivity. However, an unexpected observation was that knockdown of NYGGF4 reduced intracellular ATP concentration and promoted an increase in mitochondrial transmembrane potential (ΔΨm) and reactive oxygen species (ROS) level without affecting mitochondrial morphology or mtDNA. Therefore, the role of NYGGF4 in mitochondrial function remains unclear, and further animal studies are needed to explore the biological function of this gene.
Assuntos
Adipócitos/metabolismo , Proteínas de Transporte/genética , Resistência à Insulina/genética , Mitocôndrias/genética , Células 3T3-L1 , Adipócitos/fisiologia , Adipócitos/ultraestrutura , Análise de Variância , Animais , Primers do DNA/genética , DNA Complementar/genética , Técnicas de Silenciamento de Genes , Glucose/metabolismo , Potencial da Membrana Mitocondrial/fisiologia , Camundongos , Microscopia Eletrônica , Mitocôndrias/fisiologia , Plasmídeos/genética , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
Uncoupling proteins (UCPs) located in the inner mitochondrial membrane are involved in the regulation of energy balance. Thus far, 5 UCP isoforms have been identified, but controversies exist in the research focused on the function of the UCPs (except UCP1) in the pathogenesis of obesity. Because of the known cross-reactivity of the antibodies presently available for the detection of UCP proteins, this study systematically analyzed the differential tissue expression profiles of the 5 UCP isoforms in lean control mice and ob/ob mice by using real-time polymerase chain reaction (PCR) analysis. The results show that the tissue-specific expression patterns of individual isoforms in normal and ob/ob mice are considerably different; this will provide new insights into the functions of UCPs in the pathogenesis of genetic obesity.
Assuntos
Perfilação da Expressão Gênica , Canais Iônicos/genética , Proteínas Mitocondriais/genética , Obesidade/genética , Animais , Regulação da Expressão Gênica/fisiologia , Camundongos , Camundongos Obesos , Obesidade/etiologia , Especificidade de Órgãos , Reação em Cadeia da Polimerase , Proteína Desacopladora 1RESUMO
We have undertaken cDNA microarrays to identify differentially expressed genes in the prefrontal cortex (PFC) of spontaneously hypertensive-rat (SHR), a rodent model of attention deficit hyperactivity disorder (ADHD) versus control Wistar-Kyoto (WKY) rats. The analysis of the gene expression profiles indicated that 57 genes were up-regulated and 97 genes were down-regulated in the PFC of SHR. These predominately expressed genes included genes involved in neural development, immunity, transcription factor, monoamine neurotransmitter, metabolism, signal transduction, apoptosis and so on. Although more detailed analyses are necessary, it is anticipated that further study of genes identified will provide insights into their specific roles in the etiology of ADHD.
Assuntos
Perfilação da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos , Córtex Pré-Frontal/metabolismo , Animais , Regulação da Expressão Gênica , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: To evaluate the feasibility of auditory monitoring of neurophysiological status using frequency-following response (FFR) in neonates with progressive moderate hyperbilirubinemia, measured by transcutaneous (TcB) levels. STUDY DESIGN: ABR and FFR measures were compared and correlated with TcB levels across three groups. Group I was a healthy cohort (n = 13). Group II (n = 28) consisted of neonates with progressive, moderate hyperbilirubinemia and Group III consisted of the same neonates, post physician-ordered phototherapy. RESULT: FFR amplitudes in Group I controls (TcB = 83.1 ± 32.5µmol/L; 4.9 ± 1.9 mg/dL) were greater than Group II (TcB = 209.3 ± 48.0µmol/L; 12.1 ± 2.8 mg/dL). After TcB was lowered by phototherapy, FFR amplitudes in Group III were similar to controls. Lower TcB levels correlated with larger FFR amplitudes (r = -0.291, p = 0.015), but not with ABR wave amplitude or latencies. CONCLUSION: The FFR is a promising measure of the dynamic neurophysiological status in neonates, and may be useful in tracking neurotoxicity in infants with hyperbilirubinemia.
Assuntos
Estimulação Acústica , Tronco Encefálico/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico , Hiperbilirrubinemia Neonatal/fisiopatologia , Triagem Neonatal/métodos , Bilirrubina/sangue , Estudos de Coortes , Eletroencefalografia , Humanos , Hiperbilirrubinemia Neonatal/sangue , Hiperbilirrubinemia Neonatal/terapia , Recém-Nascido , Fototerapia , FalaRESUMO
AIM: NYGGF4 is a novel gene that is abundantly expressed in the adipose tissue of obese patients. The purpose of this study was to investigate the effects of NYGGF4 on basal and insulin-stimulated glucose uptake in mature 3T3-L1 adipocytes and to understand the underlying mechanisms. METHODS: 3T3-L1 preadipocytes transfected with either an empty expression vector (pcDNA3.1Myc/His B) or an NYGGF4 expression vector were differentiated into mature adipocytes. Glucose uptake was determined by measuring 2-deoxy-D-[3H]glucose uptake into the adipocytes. Immunoblotting was performed to detect the translocation of insulin-sensitive glucose transporter 4 (GLUT4). Immunoblotting also was used to measure the phosphorylation and total protein contents of insulin signaling proteins such as the insulin receptor (IR), insulin receptor substrate (IRS)-1, Akt, ERK1/2, p38, and JNK. RESULTS: NYGGF4 over-expression in 3T3-L1 adipocytes reduced insulin-stimulated glucose uptake and impaired insulin-stimulated GLUT4 translocation. It also diminished insulin-stimulated tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, p38, and JNK. CONCLUSION: NYGGF4 regulates the functions of IRS-1 and Akt, decreases GLUT4 translocation and reduces glucose uptake in response to insulin. These observations highlight the potential role of NYGGF4 in glucose homeostasis and possibly in the pathogenesis of obesity.
Assuntos
Células 3T3-L1/metabolismo , Proteínas de Transporte/metabolismo , Glucose/metabolismo , Animais , Proteínas de Transporte/genética , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Humanos , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologiaRESUMO
To investigate the gene expression profiles of adipose tissue of obese rats after central administration of neuropeptide Y-Y5 receptor antisense oligodeoxynucleotides (ODNs), Y5 receptor antisense, mismatched ODNs or vehicle was intracerebroventricularly injected and cDNA microarrays were undertaken. Central administration of NPY-Y5 receptor antisense ODNs decreased food intake, body weight and serum insulin compared with both vehicle and mismatched ODNs. The average area of adipocytes both at retroperitoneal and epididymal adipose tissue were fall in antisense group while only the weight of the retroperitoneal fat pats was reduced in antisense group. cDNA microarrays containing 18,000 genes/Ests were used to investigate gene expression of adipose tissue. Autoradiographic analysis showed that 404, 81, and 34 genes were differently expressed over twofold, threefold, and fivefold, respectively. The analysis of gene expression profiles indicated that 332 genes were up-regulated and 187 genes were down-regulated in response to Y5 receptor antisense ODNs treatment. Different clusters of genes associated with apoptosis, signal transduction, energy metabolism, lipid metabolism, etc., such as FXR1, PHLDA1, MAEA, PIK3R1, ICAM2, PITPN, CALM2, CAMK2D, PKIA, DRD2, SLC25A14, CKB, AADAC, LIPA, ACOX3, FADS1, were concerned. Analysis of differentially expressed genes will help to understand the effects of Y5 receptor antisense ODNs therapy.
Assuntos
Tecido Adiposo/metabolismo , Receptores de Neuropeptídeo Y/genética , Adipócitos Brancos/efeitos dos fármacos , Animais , Ingestão de Alimentos/efeitos dos fármacos , Perfilação da Expressão Gênica , Insulina/sangue , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Oligonucleotídeos Antissenso/farmacologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Study advances with a childhood case of partial deletion of the long arm of chromosome 7. The patient is a 36-month-old girl with growth retardation, mild mental retardation and delayed bone age. She showed no signs of hypotelorism, upslanting palpebral fissures, epicanthal folds, low-set ears, or flat and broad nasal bridge. Microarray testing using the Affymetrix CytoScan HD array revealed an approximately 58 kb deletion at 7q31.1 in the girl and her father, suggesting paternal origin. As the patient had no characteristic facial features, 7q deletions had not been considered. This case broadens the range of case presentations for microdeletions of chromosome 7.
RESUMO
The current study aimed to investigate the possible role of Homer 1a in the etiology and pathogenesis of attention deficit hyperactivity disorder (ADHD). We divided 32 rats into four groups. The rats in the RNAi-MPH group were given the lentiviral vector containing Homer 1a-specific miRNA (Homer 1a-RNAi-LV) by intracerebroventricular injection, and 7 days later they were given three daily doses of methylphenidate (MPH) by intragastric gavage. The RNAi-SAL group was given Homer 1a-RNAi-LV and saline later. The NC-MPH group was given the negative control lentiviral vector (NC-LV) and MPH later. The NC-SAL group was given NC-LV and saline later. Rats that were given Homer 1a RNAi exhibited increased locomotor activity and non-selective attention, and impaired learning and memory abilities, which is in line with the behavioral findings of animal models of ADHD. However, MPH ameliorated these abnormal behaviors. All findings indicated that Homer 1a may play an important role in the etiology and pathogenesis of ADHD.
Assuntos
Atenção/fisiologia , Proteínas de Transporte/fisiologia , Aprendizagem/fisiologia , Atividade Motora/fisiologia , Animais , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Proteínas de Transporte/administração & dosagem , Vetores Genéticos/administração & dosagem , Proteínas de Arcabouço Homer , Infusões Intraventriculares , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Memória/fisiologia , Metilfenidato/administração & dosagem , MicroRNAs/administração & dosagem , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Attention-deficit/hyperactivity disorder (ADHD) is a pervasive neurobehavioral disorder. We previously demonstrated differential expression of some isoforms of Homer, a family of scaffolding proteins localized to the postsynaptic density of glutamatergic excitatory synapses, in the spontaneous hypertensive rat (SHR), which is the most frequently used animal model of ADHD. Since these changes were observed in the prefrontal cortex (PFC), a critical structure in ADHD, it was hypothesized that these Homer isoforms may play a role in ADHD. The present study aimed to extend these findings to the hippocampus, which has direct connections to the PFC and subserves attention and cognition, two functions that are disturbed in ADHD. Hippocampal mRNA and protein expression of several Homer isoforms were investigated in both SHR and control Wistar-Kyoto (WKY) rats using reverse transcription-polymerase chain reaction and Western blotting, respectively. Both mRNA and protein for Homer 1a and Homer 2a/b, but not Homer 1b/c, were expressed at significantly lower levels in the hippocampus of SHR compared to WKY rats. The effects of methylphenidate (MPH) on spatial learning and memory in SHRs were also examined using the Morris water maze and on hippocampal expression of Homer isoforms. MPH improved spatial learning and memory and up-regulated hippocampal expression of Homer 1a and Homer 2a/b, but not Homer 1b/c, in SHRs. The animal model of ADHD may have altered expression of Homer 1a and Homer 2a/b in the hippocampus, in addition to the PFC. Future studies will focus on elucidating the specific mechanisms of Homer 1a and Homer 2a/b in ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Proteínas de Transporte/metabolismo , Hipocampo/metabolismo , Animais , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Proteínas de Transporte/genética , Modelos Animais de Doenças , Inibidores da Captação de Dopamina/uso terapêutico , Proteínas de Arcabouço Homer , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Metilfenidato/uso terapêutico , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
Hyperglycemia and high free fatty acids (FFAs) are two well-known characteristics of type 2 diabetes, and are also implicated in the etiology of insulin resistance. However, their roles in mitochondrial dysfunction of white adipocytes are not well-studied. In this study, we investigated the effects of high glucose (25 mM), high free fatty acids (FFAs, 1mM), or a combination of both high glucose+high FFAs on mitochondrial function in differentiated 3T3-L1 adipocytes after 48 h of treatment. We found that high glucose, high FFAs, or high glucose+high FFAs reduced insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes. In addition, the mitochondria became smaller and more compact. Levels of the mitofusion protein mfn1 decreased and levels of the mitofission protein Drp1 increased as compared to controls. NRF1 was downregulated, and PGC-1 beta levels were diminished in the high glucose and high glucose+high FFAs conditions. Levels of PGC-1 alpha and mtTFA mRNA were greatly downregulated. No difference was found in the mitochondrial DNA (mtDNA) and intracellular ATP levels of treated cells compared to control cells. Cells treated with high glucose or high FFAs accumulated significant amounts of reactive oxygen species (ROS) and displayed a loss of the mitochondrial membrane potential. High glucose and high glucose+high FFAs led to similar decreases in intramitochondrial calcium concentration, although high FFAs had no effect. Therefore, high glucose and high FFAs can regulate insulin sensitivity, and mitochondrial dysfunction may occur in this process.
Assuntos
Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Ácidos Graxos não Esterificados/farmacologia , Glucose/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Células 3T3-L1 , Trifosfato de Adenosina/metabolismo , Adipócitos/citologia , Adipócitos/ultraestrutura , Animais , Cálcio/metabolismo , DNA Mitocondrial/metabolismo , Insulina/farmacologia , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/ultraestrutura , Espécies Reativas de Oxigênio/metabolismoRESUMO
TNF-alpha was the first proinflammatory cytokine identified linking obesity, insulin resistance and chronic inflammation. However, the mechanism of TNF-alpha in the etiology of insulin resistance is still far from clear. Because the mitochondria play an important role in energy metabolism, we investigated whether mitochondrial dysfunction is involved in pathogenesis of TNF-alpha-mediated insulin resistance. First, a fully differentiated insulin-resistant 3T3-L1 adipocyte model was established by incubating with 4 ng/ml TNF-alpha for 4 d, and then the mitochondrial morphology and functions were observed. TNF-alpha treatment induced pronounced morphological changes in the mitochondria, which became smaller and condensed, and some appeared hollow and absent of cristae. Mitochondrial dynamics changes were observed as increased mitofusion protein mfn1 and mitofission protein Drp1 levels compared with controls. No obvious effects on mitochondrial biogenesis were found. PGC-1alpha levels decreased, but no significant changes were found in mtTFA mRNA expression, NRF1mRNA expression and mitochondrial DNA (mtDNA). TNFalpha treatment also led to decreased mitochondrial membrane potential and reduced production of intracellular ATP, as well as accumulation of significant amounts of reactive oxygen species (ROS). Further research is required to determine if mitochondrial dysfunction is involved in the inflammatory mechanism of insulin resistance and may be a potential target for the treatment of insulin resistance.