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1.
Metabolism ; 109: 154296, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32562799

RESUMO

RATIONALE: ApoC2 is an important activator for lipoprotein lipase-mediated hydrolysis of triglyceride-rich plasma lipoproteins. ApoC2-deficient patients display severe hypertriglyceridemia (sHTG) and recurrent acute pancreatitis. However, due to embryonic lethality in ApoC2 deleted mouse extensive understanding of ApoC2 function is limited in mammalian species. OBJECTIVE: We sought to generate an animal model with ApoC2 deficiency in a rodent with some human-like features and then study the precise effects of ApoC2 on lipid and glucose homeostasis. METHODS AND RESULTS: Using CRISPR/Cas9, we deleted Apoc2 gene from golden Syrian hamster and the homozygous (-/-) pups can be born in matured term but exhibited neonatal lethality. By continuous iv administration of normal hamster serum the ApoC2-/- pups could survive till weaning and displayed severe HTG in adulthood on chow diet. A single iv injection of AAV-hApoC2 at birth can also rescue the neonatal death of ApoC2-/- pups. Adult ApoC2-/-hamsters exhibited a unique phenotype of sHTG with hypoglycemia, hypoinsulinemia and spontaneous atherosclerosis. The sHTG in ApoC2-/- adult hamsters could not be corrected by various lipid-lowering medications, but partially ameliorated by medium chain triglyceride diet and completely corrected by AAV-hApoC2. CONCLUSIONS: Our study provides a novel ApoC2-deleted mammalian model with severe hypertriglyceridemia that was fully characterized and highlights a potential therapeutic approach for the treatment of ApoC2 deficient patients.


Assuntos
Apolipoproteína C-II/deficiência , Aterosclerose/etiologia , Hipertrigliceridemia/etiologia , Animais , Animais Recém-Nascidos/genética , Apolipoproteína C-II/uso terapêutico , Glicemia , Cricetinae , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Homeostase , Humanos , Hipertrigliceridemia/tratamento farmacológico , Lipídeos , Mesocricetus
2.
Anim Genet ; 51(2): 336-340, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31960458

RESUMO

Sheep, an important source of meat, dairy products and wool, play an essential part in the global agricultural economy. Body weight and body conformation are key traits in the sheep industry; however, their underlying genetic mechanisms are poorly understood. In this study, a GWAS was implemented to identify promising genes possibly linked to birth weight (BW) and body conformation traits in neonatal sheep, using a high-throughput chip (630 K). After quality control, 277 individuals and 518 203 variants were analyzed using gemma software in a mixed linear model. A total of 48 genome-wide suggestive SNPs were obtained, of which four were associated with BW, four with withers height (WH), 11 with body length (BL) and 29 with chest girth (CG). In total, 39 genes associated with BW and body conformation traits were identified by aligning to the sheep genome (Ovis aries_v4.0), and most of them were involved in the cell cycle and body development. Promising candidate genes found included the following: FOS like 2 or AP-1 transcription factor subunit (FOSL2) for BW; potassium voltage-gated channel subfamily D member 2 (KCND2) for WH; transmembrane protein 117 (TMEM117), transforming growth factor beta induced (TGFBI), and leukocyte cell-derived chemotaxin 2 (LECT2) for BL; and trafficking kinesin protein 1 (TRAK1) and LOC101102529 for CG. These results provide cues for similar studies aiming at uncovering the genetic mechanisms underlying body development, and marker-assisted selection programs focusing on BW and body conformation traits in sheep.


Assuntos
Animais Recém-Nascidos/genética , Tamanho Corporal/genética , Peso Corporal/genética , Estudo de Associação Genômica Ampla/veterinária , Polimorfismo de Nucleotídeo Único , Carneiro Doméstico/fisiologia , Animais , Peso ao Nascer/genética , Estatura/genética , Humanos , Modelos Lineares , Modelos Genéticos , Carneiro Doméstico/genética
3.
BMC Vet Res ; 15(1): 395, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694632

RESUMO

BACKGROUND: Weight at birth is an important predictor of neonatal mortality and morbidity in dogs. In addition, the birthweight of the puppies in a litter influences the decision to perform a cesarean section. The goal of the present study was to estimate heritabilities for the puppy birth weight in Labrador retrievers. RESULTS: Of the 1138 Labrador retriever litters whelped at the Guiding Eye for the Blind between September 2001 and February 2018, 1013 were included in the analyses after data editing. Puppy weight at birth was the target trait, measured on a continuous scale in pounds, and converted to grams. Linear mixed models were used to identify factors influencing puppy weight at birth. The analyses showed that the sex of the puppy, litter size, length of gestation, adult weight of the dam, parity, year of birth and inbreeding coefficient of the puppies and dams contributed to the variance of the puppy birth weight. Dam and litter effects were included as random effects. A multiple trait derivative free restricted maximum likelihood approach was used to estimate variance components and genetic parameters with two animal models, one without covariates (Model 1) and one with covariates (Model 2). Sex of the puppy and litter size had moderate effects, whereas gestation length, adult weight of the dam, parity, year of birth and inbreeding coefficients of the dam and the puppies had minor effects. Estimates for Model 1 and Model 2 were 0.21 and 0.17 for the direct heritabilities, 0.22 and 0.22 for the maternal additive genetic heritabilities, 0.07 and 0.07 for the maternal permanent environmental proportions, and 0.14 and 0.08 for the environmental proportion of the litter. CONCLUSIONS: In order to estimate reliable breeding values for puppy weight at birth, sex of puppy, litter size, length of gestation and the adult weight of the dam should be included. Estimates could benefit from weighing the dams prior to each mating.


Assuntos
Animais Recém-Nascidos/genética , Peso ao Nascer/genética , Cães/genética , Animais , Animais Recém-Nascidos/fisiologia , Peso ao Nascer/fisiologia , Feminino , Idade Gestacional , Endogamia , Modelos Lineares , Tamanho da Ninhada de Vivíparos , Masculino , Paridade , Gravidez
4.
Genes (Basel) ; 10(10)2019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31557843

RESUMO

Skeletogenesis is complex and incompletely understood. Derangement of this process likely underlies developmental skeletal pathologies. Examination of tissue-specific gene expression may help elucidate novel skeletal developmental pathways that could contribute to disease risk. Our aim was to identify and functionally annotate differentially expressed genes in equine neonatal and adult articular cartilage (AC) and subchondral bone (SCB). RNA was sequenced from healthy AC and SCB from the fetlock, hock, and stifle joints of 6 foals (≤4 weeks of age) and six adults (8-12 years of age). There was distinct clustering by age and tissue type. After differential expression analysis, functional annotation and pathway analysis were performed using PANTHER and Reactome. Approximately 1115 and 3574 genes were differentially expressed between age groups in AC and SCB, respectively, falling within dozens of overrepresented gene ontology terms and enriched pathways reflecting a state of growth, high metabolic activity, and tissue turnover in the foals. Enriched pathways were dominated by those related to extracellular matrix organization and turnover, and cell cycle and signal transduction. Additionally, we identified enriched pathways related to neural development and neurotransmission in AC and innate immunity in SCB. These represent novel potential mechanisms for disease that can be explored in future work.


Assuntos
Animais Recém-Nascidos/genética , Osso e Ossos/metabolismo , Cartilagem Articular/metabolismo , Cavalos/genética , Animais , Feminino , Expressão Gênica , Masculino , Análise de Sequência de RNA , Transcriptoma
5.
Free Radic Biol Med ; 145: 103-117, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31553938

RESUMO

Mitochondrial dysfunction is associated with obesity-induced cardiac remodelling. Recent research suggests that the cristae are the true bioenergetic components of cells. Acetylcholine (ACh), the major neurotransmitter of the vagus nerve, exerts cardio-protective effects against ischaemia. This study investigated the role of cristae remodelling in palmitate (PA)-induced neonatal rat cardiomyocyte hypertrophy and explored the beneficial effects of ACh. We found loose, fragmented and even lysed cristae in PA-treated neonatal cardiomyocytes along with declines in mitochondrial network and complex expression and overproduction of mitochondrial reactive oxygen species (ROS); these changes ultimately resulted in increased myocardial size. Overexpression of mitofilin by adenoviral infection partly improved cristae shape, mitochondrial network, and ATP content and attenuated cell hypertrophy. Interestingly, siRNA-mediated AMP-activated protein kinase (AMPK) silencing increased the number of cristae with a balloon-like morphology without disturbing mitofilin expression. Furthermore, AMPK knockdown abolished the effects of mitofilin overexpression on cristae remodelling and inhibited the interaction of mitofilin with sorting and assembly machinery 50 (Sam50) and coiled-coil helix coiled-coil helix domain-containing protein 3 (CHCHD3), two core components of the mitochondrial contact site and cristae organizing system (MICOS) complex. Intriguingly, ACh upregulated mitofilin expression and AMPK phosphorylation via the muscarinic ACh receptor (MAChR). Moreover, ACh enhanced protein-protein interactions between mitofilin and other components of the MICOS complex, thereby preventing PA-induced mitochondrial dysfunction and cardiomyocyte hypertrophy; however, these effects were abolished by AMPK silencing. Taken together, our data suggest that ACh improves cristae remodelling to defend against PA-induced myocardial hypertrophy, presumably by increasing mitofilin expression and activating AMPK to form the MICOS complex through MAChR. These results suggest new and promising therapeutic approaches targeting mitochondria to prevent lipotoxic cardiomyopathy.


Assuntos
Quinase 2 de Receptor Acoplado a Proteína G/genética , Hipertrofia/tratamento farmacológico , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Proteínas Musculares/genética , Proteínas Quinases/genética , Acetilcolina/metabolismo , Animais , Animais Recém-Nascidos/genética , Remodelamento Atrial/efeitos dos fármacos , Remodelamento Atrial/genética , Modelos Animais de Doenças , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipertrofia/induzido quimicamente , Hipertrofia/metabolismo , Hipertrofia/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Proteínas Mitocondriais/metabolismo , Proteínas Musculares/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Palmitatos/toxicidade , Fosforilação , Mapas de Interação de Proteínas/efeitos dos fármacos , Transporte Proteico , RNA Interferente Pequeno/farmacologia , Ratos , Nervo Vago/efeitos dos fármacos , Nervo Vago/patologia
6.
Biomed Res Int ; 2019: 9573248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467920

RESUMO

The neonatal immune system is still immature, which makes it more susceptible to the infectious agents. Neonatal immune activation is associated with increased permeability of the blood-brain barrier, causing an inflammatory cascade in the CNS and altering behavioral and neurochemical parameters. One of the hypotheses that has been studied is that neuroinflammation may be involved in neurodegenerative processes, such as Alzheimer's disease (AD). We evaluate visuospatial memory, cytokines levels, and the expression of tau and GSK-3ß proteins in hippocampus and cortex of animals exposed to neonatal endotoxemia. C57BL/6 mice aging two days received a single injection of subcutaneous lipopolysaccharide (LPS). At 60,120, and 180 days of age, visual-spatial memory was evaluated and the hippocampus and cortex were dissected to evaluate the cytokines levels and expression of tau and GSK-3ß proteins. The animals exposed to LPS in the neonatal period present with visuospatial memory impairment at 120 and 180 days of age. Here there was an increase of TNF-α and IL-1ß levels in the hippocampus and cortex only at 60 days of age. Here there was an increase in the expression of GSK-3ß in hippocampus of the animals at 60, 120, and 180 days of age. In the cortex, this increase occurred in the 120 and 180 days of age. Tau protein expression was high in hippocampus and cortex at 120 days of age and in hippocampus at 180 days of age. The data observed show that neonatal immune activation may be associated with visuospatial memory impairment, neuroinflammation, and increased expression of GSK-3ß and Tau proteins in the long term.


Assuntos
Animais Recém-Nascidos/imunologia , Encéfalo/imunologia , Endotoxemia/imunologia , Inflamação/imunologia , Animais , Animais Recém-Nascidos/genética , Barreira Hematoencefálica/imunologia , Encéfalo/crescimento & desenvolvimento , Córtex Cerebelar/imunologia , Endotoxemia/induzido quimicamente , Glicogênio Sintase Quinase 3 beta/genética , Hipocampo/imunologia , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Lipopolissacarídeos/toxicidade , Camundongos , Proteínas tau/genética
7.
J Dairy Sci ; 102(8): 7038-7048, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31178190

RESUMO

Circular RNA (circRNA) have been suggested to contribute to regulating gene expression in various tissues and cells of eukaryotes. However, little is known regarding the expression pattern of circRNA and their potential function in the small intestine of neonatal calves that receive colostrum. In the current study, jejunum tissue samples were collected from control calves (2 h after birth; CT; n = 3) and neonatal calves that ingested colostrum (24 h after birth; CO; n = 3) or milk (24 h after birth; MK; n = 3) to compare the circRNA expression patterns using a high-throughput RNA sequencing approach. A total of 21,213, 17,861, and 21,737 circRNA were identified in the CT, CO, and MK groups, respectively. Only 13,254 of these circRNA were common to the 3 groups, suggesting high specificity of circRNA expression depending on nutrient type. In total, 243, 249, and 283 circRNA were differentially expressed in the CO versus CT, CO versus MK, and MK versus CT comparisons, respectively. Gene ontology analysis showed that the differentially expressed circRNA and their predicted or known target genes from the CO and MK groups were mainly involved in macromolecule metabolic process, response to stress, and vesicle-mediated transport. Moreover, pathway analysis showed that the Rap1 signaling pathway, focal adhesion, ubiquitin-mediated proteolysis, and extracellular matrix-receptor interaction were the most significantly enriched pathways. These data collectively indicate that circRNA are abundant and dynamically expressed when calves receive colostrum and act as microRNA sponges to regulate their target genes for jejunum function during the early development of newborn calves.


Assuntos
Animais Recém-Nascidos/metabolismo , Bovinos/metabolismo , Colostro/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , MicroRNAs/metabolismo , RNA/metabolismo , Animais , Animais Recém-Nascidos/genética , Animais Recém-Nascidos/crescimento & desenvolvimento , Bovinos/genética , Bovinos/crescimento & desenvolvimento , Feminino , Intestino Delgado/metabolismo , Jejuno/metabolismo , MicroRNAs/genética , Leite/metabolismo , Gravidez , RNA/genética , RNA Circular , Transdução de Sinais
8.
Br Poult Sci ; 60(4): 366-372, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31046426

RESUMO

1. In current breeding programmes, uniformity of end products and producing animals that are robust to environmental challenges are desirable. Several studies have provided evidence of the presence of genetic heterogeneity of residual variance and proposed that it could be possible to increase uniformity of livestock productions by selection. The present study aimed to define the micro environmental sensitivity of dual-purpose chickens for body weight at hatch. 2. The data set consisted of 24,321 female and 21,547 male chickens' records of hatch weight from 19 consecutive generations of Mazandaran fowl. The statistical analysis was carried out in a two-step approach: first, an animal model was fitted to the data and then, the impact of additive genetic effects on the residual variance of the studied trait was investigated. 3. The estimate of heritability for body weight at hatch was in the range of 0.23-0.25 for female and 0.14-0.16 for male offspring, respectively. The proportion of maternal environmental variance to phenotypic variance ranged from 0.24 to 0.27 for female and 0.17 to 0.24 for male offspring. Heritabilities in females were higher than males. Estimates of the heritability of residual variance ranged between 0.067 and 0.090. The genetic coefficients of variation were high ranging between 0.83 and 0.86. Genetic correlations between hatch weight and its residual variance estimates from bivariate analysis were -0.39 and -0.44 in females and males, respectively. 4. The results suggest that there is an opportunity to simultaneously improve body weight and the uniformity of body weight by selecting for lower residual variance in native chickens.


Assuntos
Animais Recém-Nascidos/fisiologia , Peso Corporal/genética , Galinhas/fisiologia , Heterogeneidade Genética , Animais , Animais Recém-Nascidos/genética , Galinhas/genética , Feminino , Irã (Geográfico) , Masculino
9.
Res Vet Sci ; 124: 256-262, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30999161

RESUMO

Interferon-induced proteins with tetratricopeptide repeats (IFITs) are a family of proteins strongly induced downstream of type I interferon signaling. The function of IFITs has been investigated extensively in mammals. IFIT5 is the sole protein in this family found in birds and little information is available about the function of avian IFIT5. In this study, duck IFIT5 was cloned from peripheral blood mononuclear cells. Multiple amino acid sequence alignment and phylogenetic analysis showed that duck IFIT5 is highly homologous to chicken IFIT5. Tissue specificity analysis demonstrated that duck IFIT5 was ubiquitously expressed in all examined tissues of five-day-old ducklings, with the highest expression levels in heart, followed by thymus, cerebrum, liver, and lung; kidney expressed the lowest. Quantitative real-time PCR (qRT-PCR) analysis revealed that duck IFIT5 expression rapidly increased both in vitro and in vivo after stimulation with polyinosinic:polycytidylic acid [poly (I:C)] and infection with virulent duck hepatitis A virus type 3 (DHAV-3), respectively. Altogether, these results indicate that the expression of duck IFIT5 is positively correlated with viral load and may play an important role in the immune response to DHAV-3 infection. This study lays a foundation for further research into the innate antiviral immune responses of ducklings.


Assuntos
Patos/genética , Patos/imunologia , Proteínas de Neoplasias/genética , Sequência de Aminoácidos , Animais , Animais Recém-Nascidos/genética , Animais Recém-Nascidos/imunologia , Proteínas Aviárias/química , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Sequência de Bases , Clonagem Molecular , Vírus da Hepatite do Pato/fisiologia , Hepatite Viral Animal/imunologia , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Fases de Leitura Aberta , Filogenia , Infecções por Picornaviridae/imunologia , Infecções por Picornaviridae/veterinária , Poli I-C/farmacologia , Doenças das Aves Domésticas/imunologia , Alinhamento de Sequência
10.
PLoS Genet ; 15(3): e1007810, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30893341

RESUMO

Spermatogenesis is the process by which male gametes are formed from a self-renewing population of spermatogonial stem cells (SSCs) residing in the testis. SSCs represent less than 1% of the total testicular cell population in adults, but must achieve a stable balance between self-renewal and differentiation. Once differentiation has occurred, the newly formed and highly proliferative spermatogonia must then enter the meiotic program in which DNA content is doubled, then halved twice to create haploid gametes. While much is known about the critical cellular processes that take place during the specialized cell division that is meiosis, much less is known about how the spermatocytes in the "first-wave" in juveniles compare to those that contribute to long-term, "steady-state" spermatogenesis in adults. Given the strictly-defined developmental process of spermatogenesis, this study explored the transcriptional profiles of developmental cell stages during testis maturation. Using a combination of comprehensive germ cell sampling with high-resolution, single-cell-mRNA-sequencing, we have generated a reference dataset of germ cell gene expression. We show that discrete developmental stages of spermatogenesis possess significant differences in the transcriptional profiles from neonates compared to juveniles and adults. Importantly, these gene expression dynamics are also reflected at the protein level in their respective cell types. We also show differential utilization of many biological pathways with age in both spermatogonia and spermatocytes, demonstrating significantly different underlying gene regulatory programs in these cell types over the course of testis development and spermatogenic waves. This dataset represents the first unbiased sampling of spermatogonia and spermatocytes during testis maturation, at high-resolution, single-cell depth. Not only does this analysis reveal previously unknown transcriptional dynamics of a highly transitional cell population, it has also begun to reveal critical differences in biological pathway utilization in developing spermatogonia and spermatocytes, including response to DNA damage and double-strand breaks.


Assuntos
Células-Tronco Germinativas Adultas/fisiologia , Análise de Célula Única/métodos , Espermatogênese/genética , Animais , Animais Recém-Nascidos/genética , Diferenciação Celular , Perfilação da Expressão Gênica/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Diferenciação Sexual , Espermatócitos/fisiologia , Espermatogônias/fisiologia , Testículo/embriologia , Testículo/fisiologia , Transcriptoma/genética
11.
Proc Natl Acad Sci U S A ; 116(8): 3262-3267, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30728295

RESUMO

Patterned spontaneous activity periodically displays in developing retinas termed retinal waves, essential for visual circuit refinement. In neonatal rodents, retinal waves initiate in starburst amacrine cells (SACs), propagating across retinal ganglion cells (RGCs), further through visual centers. Although these waves are shown temporally synchronized with transiently high PKA activity, the downstream PKA target important for regulating the transmission from SACs remains unidentified. A t-SNARE, synaptosome-associated protein of 25 kDa (SNAP-25/SN25), serves as a PKA substrate, implying a potential role of SN25 in regulating retinal development. Here, we examined whether SN25 in SACs could regulate wave properties and retinogeniculate projection during development. In developing SACs, overexpression of wild-type SN25b, but not the PKA-phosphodeficient mutant (SN25b-T138A), decreased the frequency and spatial correlation of wave-associated calcium transients. Overexpressing SN25b, but not SN25b-T138A, in SACs dampened spontaneous, wave-associated, postsynaptic currents in RGCs and decreased the SAC release upon augmenting the cAMP-PKA signaling. These results suggest that SN25b overexpression may inhibit the strength of transmission from SACs via PKA-mediated phosphorylation at T138. Moreover, knockdown of endogenous SN25b increased the frequency of wave-associated calcium transients, supporting the role of SN25 in restraining wave periodicity. Finally, the eye-specific segregation of retinogeniculate projection was impaired by in vivo overexpression of SN25b, but not SN25b-T138A, in SACs. These results suggest that SN25 in developing SACs dampens the spatiotemporal properties of retinal waves and limits visual circuit refinement by phosphorylation at T138. Therefore, SN25 in SACs plays a profound role in regulating visual circuit refinement.


Assuntos
Sinalização do Cálcio/genética , Retina/metabolismo , Proteína 25 Associada a Sinaptossoma/genética , Vias Visuais/fisiologia , Potenciais de Ação/genética , Células Amácrinas/metabolismo , Células Amácrinas/fisiologia , Animais , Animais Recém-Nascidos/genética , Animais Recém-Nascidos/crescimento & desenvolvimento , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Técnicas de Patch-Clamp , Fosforilação , Ligação Proteica , Retina/crescimento & desenvolvimento , Retina/fisiologia , Células Ganglionares da Retina/metabolismo , Potenciais Sinápticos/genética
12.
Br Poult Sci ; 60(1): 71-78, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30444128

RESUMO

1. The present study was conducted to investigate whether brain somatostatin increases feed intake in neonatal chickens. The mediating role of neuropeptide Y receptors on feed intake induced by somatostatin was investigated. 2. In this study, seven experiments were designed, each with four treatment groups (n = 44 in each experiment). In Experiment 1, chicks received control solution and 0.5, 1 and 2 nmol of somatostatin through intracerebroventricular (ICV) injection. In experiments 2, 3 and 4, chickens were ICV injected with control solution and 1.25, 2.5 and 5 µg of B5063 (NPY1 receptor antagonist), SF22 (NPY2 receptor antagonist) and SML0891 (NPY5 receptor antagonist), respectively. In experiment 5, 6 and 7 chickens received ICV injection of B5063, SF22, SML0891, with a co-injection of + somatostatin, control solution and somatostatin. The cumulative feed intake was measured until 120 min post injection. 3. Somatostatin significantly increased feed intake in FD3 chicks. Both B5063 and SML0891 dose-dependently decreased feed intake compared with the control group, while SF22 led to a dose-dependent increase in feed intake. In addition, the hyperphagic effect of somatostatin significantly decreased with co-injection of B560 plus somatostatin (p < 0.05), but SF22 and SML0891 had no effect on feed intake induced by somatostatin in chicks (p > 0.05). 4. Based on the results of this study, it is likely that somatostatin increased feed intake and NPY1 receptor acts as a mediator in hyperphagic effect of somatostatin in neonatal chicks.


Assuntos
Proteínas Aviárias/genética , Galinhas/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Receptores de Neuropeptídeo Y/genética , Somatostatina/farmacologia , Animais , Animais Recém-Nascidos/genética , Animais Recém-Nascidos/fisiologia , Proteínas Aviárias/antagonistas & inibidores , Proteínas Aviárias/metabolismo , Galinhas/genética , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/genética , Injeções Intraventriculares/veterinária , Masculino , Distribuição Aleatória , Receptores de Neuropeptídeo Y/antagonistas & inibidores , Receptores de Neuropeptídeo Y/metabolismo , Somatostatina/administração & dosagem
13.
Brain Res Bull ; 144: 140-148, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30217735

RESUMO

Sevoflurane is an experimental potent yet volatile anesthesia agent characterized by a low blood/gas partition coefficient. However, exposure to sevoflurane in neonatal mice has been speculated to result in learning deficits and abnormal social behavior. The aim of the present study was to investigate the relationship between sevoflurane and miR-96, in an attempt to identify the means by which it mediates IGF1R to influence the cognitive dysfunction (CD) in neonatal rats. Relationship between differentially expressed miRNAs and sevoflurane concentration was identified. The potential underlying regulatory mechanisms involved with sevoflurane were investigated through the administration of varying concentrations of the agent (1%, 2% and 4%), combined with miR-96 mimic or an inhibitor. A target prediction program was utilized, while the luciferase activity was determined in order to verify whether miR-96 targets IGF1R. The mRNA and protein levels of IGF1R, Bcl-2, Bax, and caspase-3 were measured followed by the determination of hippocampal neuron apoptosis. Learning and memory performance was assessed using the Morris water maze (MWM) test and step-down test. The obtained results highlighted a positive correlation between miR-96 and the concentration of sevoflurane, while miR-96 was confirmed to negatively target IGF1R. Our analyses indicated that 4% sevoflurane had a significantly stronger effect on reducing the levels of IGF1R and Bcl-2, while elevating the levels of miR-96, Bax and caspase-3 more so than that of 1% or 2% sevoflurane, which resulted in increased hippocampal neuron apoptosis but diminished the learning and memory performance of the rats. The addition of miR-96 mimic was demonstrated to exacerbate the influence of sevoflurane on hippocampal neurons as well as the cognitive function of the rats. The key findings of our study highlighted the role of miR-96 in the potential mechanism of sevoflurane anesthesia-induced CD in neonatal rats through the downregulation of IGF1R.


Assuntos
Cognição/efeitos dos fármacos , Disfunção Cognitiva/genética , MicroRNAs/metabolismo , Anestésicos Inalatórios/farmacologia , Animais , Animais Recém-Nascidos/genética , Apoptose/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Feminino , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Éteres Metílicos/farmacologia , MicroRNAs/genética , Neurônios/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Sevoflurano/farmacologia
14.
Elife ; 72018 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-30412050

RESUMO

Unresolved ER stress followed by cell death is recognized as the main cause of a multitude of pathologies including neonatal diabetes. A systematic analysis of the mechanisms of ß-cell loss and dysfunction in Akita mice, in which a mutation in the proinsulin gene causes a severe form of permanent neonatal diabetes, showed no increase in ß-cell apoptosis throughout life. Surprisingly, we found that the main mechanism leading to ß-cell dysfunction is marked impairment of ß-cell growth during the early postnatal life due to transient inhibition of mTORC1, which governs postnatal ß-cell growth and differentiation. Importantly, restoration of mTORC1 activity in neonate ß-cells was sufficient to rescue postnatal ß-cell growth, and to improve diabetes. We propose a scenario for the development of permanent neonatal diabetes, possibly also common forms of diabetes, where early-life events inducing ER stress affect ß-cell mass expansion due to mTOR inhibition.


Assuntos
Diabetes Mellitus/genética , Estresse do Retículo Endoplasmático/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Proinsulina/genética , Animais , Animais Recém-Nascidos/genética , Animais Recém-Nascidos/crescimento & desenvolvimento , Apoptose/genética , Diabetes Mellitus/patologia , Retículo Endoplasmático/genética , Humanos , Células Secretoras de Insulina/patologia , Camundongos , Mutação , Dobramento de Proteína
15.
Nature ; 560(7719): 489-493, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30089902

RESUMO

Alterations in enteric microbiota are associated with several highly prevalent immune-mediated and metabolic diseases1-3, and experiments involving faecal transplants have indicated that such alterations have a causal role in at least some such conditions4-6. The postnatal period is particularly critical for the development of microbiota composition, host-microbe interactions and immune homeostasis7-9. However, the underlying molecular mechanisms of this neonatal priming period have not been defined. Here we report the identification of a host-mediated regulatory circuit of bacterial colonization that acts solely during the early neonatal period but influences life-long microbiota composition. We demonstrate age-dependent expression of the flagellin receptor Toll-like receptor 5 (TLR5) in the gut epithelium of neonate mice. Using competitive colonization experiments, we demonstrate that epithelial TLR5-mediated REG3γ production is critical for the counter-selection of colonizing flagellated bacteria. Comparative microbiota transfer experiments in neonate and adult wild-type and Tlr5-deficient germ-free mice reveal that neonatal TLR5 expression strongly influences the composition of the microbiota throughout life. Thus, the beneficial microbiota in the adult host is shaped during early infancy. This might explain why environmental factors that disturb the establishment of the microbiota during early life can affect immune homeostasis and health in adulthood.


Assuntos
Envelhecimento/imunologia , Animais Recém-Nascidos/imunologia , Microbioma Gastrointestinal/imunologia , Receptor 5 Toll-Like/imunologia , Envelhecimento/genética , Animais , Animais Recém-Nascidos/genética , Cruzamentos Genéticos , Meio Ambiente , Feminino , Flagelina/imunologia , Flagelina/metabolismo , Microbioma Gastrointestinal/genética , Homeostase , Interações entre Hospedeiro e Microrganismos , Abrigo para Animais , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Receptor 5 Toll-Like/genética
16.
J Agric Food Chem ; 66(29): 7684-7691, 2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-29974734

RESUMO

This study aims to investigate in ovo feeding (IOF) of creatine pyruvate (CrPyr) on glucose metabolism, hormone concentration, and the 5'-AMP-activated protein kinase (AMPK) pathway in breast muscle of embryos and neonatal broilers. The three treatments were noninjected control, 0.75% NaCl treatment, and 12 mg CrPyr/egg treatment. The solution was injected on the 17.5 day of incubation. At hatch, 120 male broilers from each treatment were chosen for a 7 day feeding trial. Compared with other treatments, CrPyr treated broilers enhanced insulin and thyroxine levels in plasma, adenosine triphosphate (ATP) concentration, hexokinase and pyruvate kinase activities, glucose transporter protein mRNA expressions, as well as protein abundances of phosphor-liver kinase B1 and phosphor-AMPK in breast muscle at hatch. In conclusion, IOF of CrPyr improved the energy status, increased the gene expression of glucose transporter proteins, and facilitated glycolysis in breast muscle, which may be associated with the activated AMPK pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Galinhas/metabolismo , Creatina/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Músculos/metabolismo , Ácido Pirúvico/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Criação de Animais Domésticos , Animais , Animais Recém-Nascidos/genética , Animais Recém-Nascidos/crescimento & desenvolvimento , Animais Recém-Nascidos/metabolismo , Galinhas/genética , Galinhas/crescimento & desenvolvimento , Feminino , Proteínas Facilitadoras de Transporte de Glucose/genética , Glicólise , Insulina/metabolismo , Masculino , Fosforilação , Tiroxina/metabolismo
17.
Sci Rep ; 8(1): 10745, 2018 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-30013139

RESUMO

Germ-free (GF) pigs have clear microbiological backgrounds, and are extensively used as large animal models in the biomedical sciences. However, investigations of the transcriptomic differences between GF and cesarean-derived conventional (CV) piglets are limited. To improve our understanding of GF pigs, and to increase the utility of pigs as an alternative non-rodent model, we used RNA sequencing to profile gene expression in five tissues (the oral mucosae, jejunum, colon, liver, and spleen) of four male GF piglets and four male CV piglets from the same litter. We identified 14 genes that were differentially expressed in all five tissues. Seven of these common differentially expressed genes (DEGs) were interferon-inducible genes, and all 14 were consistently downregulated in the GF piglets as compared to the CV piglets. Compared to the other tissues tested, the expression of transcription factors (TFs) in the colon was most affected by the absence of a microbiota. The expression patterns of immune-related genes were downregulated in the GF piglets as compared to the CV piglets, indicating that the intestinal microbiota influenced gene expression in other tissues besides the gut. Gene Ontology (GO) analysis indicated that, in pigs, the intestinal microbiota affected the expression of genes related to immune system function and development.


Assuntos
Microbioma Gastrointestinal/imunologia , Vida Livre de Germes/genética , Sistema Imunitário/crescimento & desenvolvimento , RNA Mensageiro/metabolismo , Transcriptoma/genética , Animais , Animais Recém-Nascidos/genética , Animais Recém-Nascidos/crescimento & desenvolvimento , Animais Recém-Nascidos/imunologia , Colo/metabolismo , Regulação para Baixo/imunologia , Perfilação da Expressão Gênica , Jejuno/metabolismo , Fígado/metabolismo , Masculino , Modelos Animais , Mucosa Bucal/metabolismo , Análise de Sequência de RNA , Baço/metabolismo , Suínos/genética , Suínos/crescimento & desenvolvimento , Suínos/imunologia , Transcriptoma/imunologia
18.
Horm Behav ; 102: 120-128, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29778460

RESUMO

Filial imprinting is the behavior observed in chicks during the sensitive or critical period of the first 2-3 days after hatching; however, after this period they cannot be imprinted when raised in darkness. Our previous study showed that temporal augmentation of the endogenous thyroid hormone 3,5,3'-triiodothyronine (T3) in the telencephalon, by imprinting training, starts the sensitive period just after hatching. Intravenous injection of T3 enables imprinting of chicks on days 4 or 6 post-hatching, even when the sensitive period has ended. However, the molecular mechanism of how T3 acts as a determinant of the sensitive period is unknown. Here, we show that Wnt-2b mRNA level is increased in the T3-injected telencephalon of 4-day old chicks. Pharmacological inhibition of Wnt signaling in the intermediate hyperpallium apicale (IMHA), which is the caudal area of the telencephalon, blocked the recovery of the sensitive period following T3 injection. In addition, injection of recombinant Wnt-2b protein into the IMHA helped chicks recover the sensitive period without the injection of T3. Lastly, we showed Wnt signaling to be involved in imprinting via the IMHA region on day 1 during the sensitive period. These results indicate that Wnt signaling plays a critical role in the opening of the sensitive period downstream of T3.


Assuntos
Animais Recém-Nascidos/psicologia , Galinhas , Fixação Psicológica Instintiva/efeitos dos fármacos , Telencéfalo/efeitos dos fármacos , Tri-Iodotironina/farmacologia , Proteína Wnt2/genética , Administração Intravenosa , Animais , Animais Recém-Nascidos/genética , Animais Recém-Nascidos/metabolismo , Galinhas/genética , Galinhas/crescimento & desenvolvimento , Galinhas/metabolismo , Escuridão , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Fixação Psicológica Instintiva/fisiologia , Comportamento de Nidação/efeitos dos fármacos , Fotoperíodo , Telencéfalo/metabolismo , Fatores de Tempo , Tri-Iodotironina/administração & dosagem , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genética , Proteína Wnt2/metabolismo
19.
Bull Exp Biol Med ; 164(4): 493-496, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29504097

RESUMO

Prenatal and postnatal exposure to low doses of the endocrine disruptor dichlorodiphenyltrichloroethane (DDT) leads to delayed activation of the canonical ß-catenin/Wnt signaling in zona glomerulosa and zona reticularis of the adrenal cortex in rats, which changed the rate of their postnatal development. Suppression of the Wnt pathway in zona fasciculata promotes its regeneration after DDT-induced blood circulation disorders and cell death.


Assuntos
Animais Recém-Nascidos/genética , DDT/farmacologia , Disruptores Endócrinos/farmacologia , Zona Glomerulosa/efeitos dos fármacos , Zona Reticular/efeitos dos fármacos , beta Catenina/genética , Animais , Animais Recém-Nascidos/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Wistar , Via de Sinalização Wnt , Zona Glomerulosa/crescimento & desenvolvimento , Zona Glomerulosa/metabolismo , Zona Glomerulosa/patologia , Zona Reticular/crescimento & desenvolvimento , Zona Reticular/metabolismo , Zona Reticular/patologia , beta Catenina/metabolismo
20.
J Agric Food Chem ; 66(15): 3840-3849, 2018 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-29584425

RESUMO

Leucine (Leu) plays an important role in protein synthesis and metabolism. The present study tested whether Leu supplementation in the diet for sows during late pregnancy could improve piglet birth weight, and it also investigated the possible underlying mechanism. Two hundred sows at day 70 of pregnancy were selected and assigned to four groups fed with following four diets until farrowing, respectively: corn and soybean meal-based diet group (CON), CON + 0.40% Leu, CON + 0.80% Leu, and CON + 1.20% Leu. We found that supplementing with 0.80% Leu significantly increased mean piglet birth weight ( P < 0.05). Supplementation with 0.40, 0.80, and 1.20% Leu increased the plasma concentration of Leu, while decreasing the plasma concentrations of valine (Val) and isoleucine (Ile) in both farrowing sows and newborn piglets ( P < 0.05). The protein expressions of amino acid transporters (including LAT1, SNAT1, SNAT2, 4F2hc, and rBAT) in duodenum, jejunum, ileum, longissimus dorsi muscle of newborn piglets, and placenta of sows showed a difference among the CON group and Leu supplemented groups. Expressions of p-mTOR, p-4E-BP1, and p-S6K1 in longissimus dorsi muscle were also enhanced in each of the supplemental Leu groups compared to CON ( P < 0.05). Collectively, these results indicated that 0.40-0.80% Leu supplementation during late gestation enhanced birth weight of fetal pigs by increasing protein synthesis through modulation of the plasma amino acids profile, amino acid transporters expression, and mTOR signaling pathway.


Assuntos
Leucina/metabolismo , Músculo Esquelético/metabolismo , Suínos/embriologia , Suínos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Sistemas de Transporte de Aminoácidos/genética , Sistemas de Transporte de Aminoácidos/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Recém-Nascidos/genética , Animais Recém-Nascidos/crescimento & desenvolvimento , Animais Recém-Nascidos/metabolismo , Suplementos Nutricionais/análise , Feminino , Idade Gestacional , Masculino , Gravidez , Transdução de Sinais , Suínos/genética , Serina-Treonina Quinases TOR/genética
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