RESUMO
BACKGROUND: Avena longiglumis Durieu (2n = 2x = 14) is a wild relative of cultivated oat (Avena sativa, 2n = 6x = 42) with good agronomic and nutritional traits. The plant mitochondrial genome has a complex organization and carries genetic traits of value in exploiting genetic resources, not least male sterility alleles used to generate F1 hybrid seeds. Therefore, we aim to complement the chromosomal-level nuclear and chloroplast genome assemblies of A. longiglumis with the complete assembly of the mitochondrial genome (mitogenome) based on Illumina and ONT long reads, comparing its structure with Poaceae species. RESULTS: The complete mitochondrial genome of A. longiglumis can be represented by one master circular genome being 548,445 bp long with a GC content of 44.05%. It can be represented by linear or circular DNA molecules (isoforms or contigs), with multiple alternative configurations mediated by long (4,100-31,235 bp) and medium (144-792 bp) size repeats. Thirty-five unique protein-coding genes, three unique rRNA genes, and 11 unique tRNA genes are identified. The mitogenome is rich in duplications (up to 233 kb long) and multiple tandem or simple sequence repeats, together accounting for more than 42.5% of the total length. We identify homologous sequences between the mitochondrial, plastid and nuclear genomes, including the exchange of eight plastid-derived tRNA genes, and nuclear-derived retroelement fragments. At least 85% of the mitogenome is duplicated in the A. longiglumis nuclear genome. We identify 269 RNA editing sites in mitochondrial protein-coding genes including stop codons truncating ccmFC transcripts. CONCLUSIONS: Comparative analysis with Poaceae species reveals the dynamic and ongoing evolutionary changes in mitochondrial genome structure and gene content. The complete mitochondrial genome of A. longiglumis completes the last link of the oat reference genome and lays the foundation for oat breeding and exploiting the biodiversity in the genus.
Assuntos
Avena , Genoma Mitocondrial , Avena/genética , Diploide , Genoma Mitocondrial/genética , Melhoramento Vegetal , Genoma de Planta/genética , FilogeniaRESUMO
BACKGROUND: The BOP (Bambusoideae, Oryzoideae, and Pooideae) clade of the Poaceae has a common ancestor, with similarities to the genomes of rice, Oryza sativa (2n = 24; genome size 389 Mb) and Brachypodium, Brachypodium distachyon (2n = 10; 271 Mb). We exploit chromosome-scale genome assemblies to show the nature of genomic expansion, structural variation, and chromosomal rearrangements from rice and Brachypodium, to diploids in the tribe Aveneae (e.g., Avena longiglumis, 2n = 2x = 14; 3,961 Mb assembled to 3,850 Mb in chromosomes). RESULTS: Most of the Avena chromosome arms show relatively uniform expansion over the 10-fold to 15-fold genome-size increase. Apart from non-coding sequence diversification and accumulation around the centromeres, blocks of genes are not interspersed with blocks of repeats, even in subterminal regions. As in the tribe Triticeae, blocks of conserved synteny are seen between the analyzed species with chromosome fusion, fission, and nesting (insertion) events showing deep evolutionary conservation of chromosome structure during genomic expansion. Unexpectedly, the terminal gene-rich chromosomal segments (representing about 50 Mb) show translocations between chromosomes during speciation, with homogenization of genome-specific repetitive elements within the tribe Aveneae. Newly-formed intergenomic translocations of similar extent are found in the hexaploid A. sativa. CONCLUSIONS: The study provides insight into evolutionary mechanisms and speciation in the BOP clade, which is valuable for measurement of biodiversity, development of a clade-wide pangenome, and exploitation of genomic diversity through breeding programs in Poaceae.
Assuntos
Brachypodium , Oryza , Oryza/genética , Brachypodium/genética , Avena/genética , Genoma de Planta/genética , Melhoramento Vegetal , CentrômeroRESUMO
The formation and maintenance of synapses require long-distance delivery of newly synthesized synaptic proteins from the soma to distal synapses, raising the fundamental question of whether impaired transport is associated with neurodevelopmental disorders such as autism. We previously revealed that syntabulin acts as a motor adapter linking kinesin-1 motor and presynaptic cargos. Here, we report that defects in syntabulin-mediated transport and thus reduced formation and maturation of synapses are one of core synaptic mechanisms underlying autism-like synaptic dysfunction and social behavioral abnormalities. Syntabulin expression in the mouse brain peaks during the first 2 weeks of postnatal development and progressively declines during brain maturation. Neurons from conditional syntabulin-/- mice (stb cKO) display impaired transport of presynaptic cargos, reduced synapse density and active zones, and altered synaptic transmission and long-term plasticity. Intriguingly, stb cKO mice exhibit core autism-like traits, including defective social recognition and communication, increased stereotypic behavior, and impaired spatial learning and memory. These phenotypes establish a new mechanistic link between reduced transport of synaptic cargos and impaired maintenance of synaptic transmission and plasticity, contributing to autism-associated behavioral abnormalities. This notion is further confirmed by the human missense variant STB-R178Q, which is found in an autism patient and loses its adapter capacity for binding kinesin-1 motors. Expressing STB-R178Q fails to rescue reduced synapse formation and impaired synaptic transmission and plasticity in stb cKO neurons. Altogether, our study suggests that defects in syntabulin-mediated transport mechanisms underlie the synaptic dysfunction and behavioral abnormalities that bear similarities to autism.
Assuntos
Transtorno Autístico , Animais , Transtorno Autístico/genética , Células Cultivadas , Humanos , Camundongos , Neurônios , Sinapses , Transmissão SinápticaRESUMO
Metastasis is the main cause of mortality in patients with cancer. Epithelial-mesenchymal transition (EMT), a crucial process in cancer metastasis, is an established target for antimetastatic drug development. LFG-500, a novel synthetic flavonoid, has been revealed as a potential antitumor agent owing to its various activities, including modulation of EMT in the inflammatory microenvironment. Here, using a transforming growth factor beta (TGF-ß)-induced EMT models, we found that LFG-500 inhibited EMT-associated migration and invasion in human breast cancer, MCF-7, and lung adenocarcinoma, A549, cell lines, consistent with the observed downregulation of YAP activity. Further studies demonstrated that LGF-500-induced suppression of YAP activation was mediated by integrin-linked kinase (ILK), suggesting that the ILK/YAP axis might be feasible target for anti-EMT and antimetastatic treatments, which was verified by a correlation analysis with clinical data and tumor specimens. Hence, our data support the use of LGF-500 as an antimetastatic drug in cancer therapy and provide evidence that the ILK/YAP axis is a feasible biomarker of cancer progression and a promising target for repression of EMT and metastasis in cancer therapy.
Assuntos
Antineoplásicos/administração & dosagem , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Flavonoides/administração & dosagem , Neoplasias/tratamento farmacológico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas de Sinalização YAP/antagonistas & inibidores , Células A549 , Animais , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos/métodos , Transição Epitelial-Mesenquimal/fisiologia , Feminino , Células Hep G2 , Humanos , Células MCF-7 , Masculino , Camundongos , Camundongos Transgênicos , Neoplasias/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/fisiologia , Proteínas de Sinalização YAP/metabolismoRESUMO
Nucleic acids generally reside in cellular aqueous solutions with mixed divalent/monovalent ions, and the competitive binding of divalent and monovalent ions is critical to the structures of nucleic acids because of their polyanionic nature. In this work, we first proposed a general and effective method for simulating a nucleic acid in mixed divalent/monovalent ion solutions with desired bulk ion concentrations via molecular dynamics (MD) simulations and investigated the competitive binding of Mg2+/Na+ ions to various nucleic acids by all-atom MD simulations. The extensive MD-based examinations show that single MD simulations conducted using the proposed method can yield desired bulk divalent/monovalent ion concentrations for various nucleic acids, including RNA tertiary structures. Our comprehensive analyses show that the global binding of Mg2+/Na+ to a nucleic acid is mainly dependent on its structure compactness, as well as Mg2+/Na+ concentrations, rather than the specific structure of the nucleic acid. Specifically, the relative global binding of Mg2+ over Na+ is stronger for a nucleic acid with higher effective surface charge density and higher relative Mg2+/Na+ concentrations. Furthermore, the local binding of Mg2+/Na+ to a phosphate of a nucleic acid mainly depends on the local phosphate density in addition to Mg2+/Na+ concentrations.
Assuntos
DNA/química , DNA/metabolismo , Magnésio/metabolismo , Conformação de Ácido Nucleico , RNA/química , RNA/metabolismo , Sódio/metabolismo , Ligação Competitiva , Simulação de Dinâmica MolecularRESUMO
Disruption of synapse assembly and maturation leads to a broad spectrum of neurodevelopmental disorders. Presynaptic proteins are largely synthesized in the soma, where they are packaged into precursor vesicles and transported into distal axons to ensure precise assembly and maintenance of presynapses. Due to their morphological features, neurons face challenges in the delivery of presynaptic cargos to nascent boutons. Thus, targeted axonal transport is vital to build functional synapses. A growing number of mutations in genes encoding the transport machinery have been linked to neurodevelopmental disorders. Emerging lines of evidence have started to uncover presynaptic mechanisms underlying axonal transport defects, thus broadening the view of neurodevelopmental disorders beyond postsynaptic mechanisms. In this review, we discuss presynaptic perspectives of neurodevelopmental disorders by focusing on impaired axonal transport and disturbed assembly and maintenance of presynapses. We also discuss potential strategies for restoring axonal transport as an early therapeutic intervention.
Assuntos
Transporte Axonal , Transtornos do Neurodesenvolvimento , Terminações Pré-Sinápticas , Humanos , Axônios , Corpo Celular , Mutação , Transtornos do Neurodesenvolvimento/genéticaRESUMO
Diploid wild oat Avena longiglumis has nutritional and adaptive traits which are valuable for common oat (A. sativa) breeding. The combination of Illumina, Nanopore and Hi-C data allowed us to assemble a high-quality chromosome-level genome of A. longiglumis (ALO), evidenced by contig N50 of 12.68 Mb with 99% BUSCO completeness for the assembly size of 3,960.97 Mb. A total of 40,845 protein-coding genes were annotated. The assembled genome was composed of 87.04% repetitive DNA sequences. Dotplots of the genome assembly (PI657387) with two published ALO genomes were compared to indicate the conservation of gene order and equal expansion of all syntenic blocks among three genome assemblies. Two recent whole-genome duplication events were characterized in genomes of diploid Avena species. These findings provide new knowledge for the genomic features of A. longiglumis, give information about the species diversity, and will accelerate the functional genomics and breeding studies in oat and related cereal crops.
Assuntos
Avena , Diploide , Genoma de Planta , Avena/genética , Cromossomos de PlantasRESUMO
Studies have shown that a series of molecular events caused by oxidative stress is associated with ferroptosis and oxidation after ischemic stroke (IS). Differential analysis was performed to identify differentially expressed mRNA (DEmRNAs) between IS and control groups. Critical module genes were identified using weighted gene co-expression network analysis (WGCNA). DEmRNAs, critical module genes, oxidative stress-related genes (ORGs), and ferroptosis-related genes (FRGs) were crossed to screen for intersection mRNAs. Candidate mRNAs were screened based on the protein-protein interaction (PPI) network and the MCODE plug-in. Biomarkers were identified based on two types of machine learning algorithms, and the intersection was obtained. Functional items and related pathways of the biomarkers were identified using gene set enrichment analysis (GSEA). Finally, single-sample GSEA (ssGSEA) and Wilcoxon tests were used to identify differential immune cells. An miRNA-mRNA-TF network was created. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the expression levels of biomarkers in the IS and control groups. There were 8287 DE mRNAs between the IS and control groups. The genes in the turquoise module were selected as critical module genes for IS. Thirty intersecting mRNAs were screened for overlaps. Seventeen candidate mRNAs were also identified. Four biomarkers (CDKN1A, GPX4, PRDX1, and PRDX6) were identified using two types of machine-learning algorithms. GSEA results indicated that the biomarkers were associated with steroid biosynthesis. Nine types of immune cells (activated B cells and neutrophils) were markedly different between the IS and control groups. We identified 3747 miRNA-mRNA-TF regulatory pairs in the miRNA-mRNA-TF regulatory network, including hsa-miR-4469-CDKN1A-BACH2 and hsa-miR-188-3p-GPX4-ATF2. CDKN1A, PRDX1, and PRDX6 were upregulated in IS samples compared with control samples. This study suggests that four biomarkers (CDKN1A, GPX4, PRDX1, and PRDX6) are significantly associated with IS. This study provides a new reference for the diagnosis and treatment of IS.
Assuntos
Ferroptose , AVC Isquêmico , MicroRNAs , Humanos , Ferroptose/genética , Estresse Oxidativo/genética , Biomarcadores , MicroRNAs/genética , RNA Mensageiro/genéticaRESUMO
Hydrolyzed royal jelly peptide (RJP) has garnered attention for its health-promoting functions. However, the potential applications of RJP in skincare have not been fully explored. In this study, we prepared RJP through the enzymatic hydrolysis of royal jelly protein with trypsin and investigated its antioxidant and anti-inflammatory properties on primary human dermal fibroblasts (HDFs). Our results demonstrate that RJP effectively inhibits oxidative damage induced by H2O2 and lipid peroxidation triggered by AAPH and t-BuOOH in HDFs. This effect may be attributed to the ability of RJP to enhance the level of glutathione and the activities of catalase and glutathione peroxidase 4, as well as its excellent iron chelating capacity. Furthermore, RJP modulates the NLRP3 inflammasome-mediated inflammatory response in HDFs, suppressing the mRNA expressions of NLRP3 and IL-1ß in the primer stage induced by LPS and the release of mature IL-1ß induced by ATP, monosodium urate, or nigericin in the activation stage. RJP also represses the expressions of COX2 and iNOS induced by LPS. Finally, we reveal that RJP exhibits superior antioxidant and anti-inflammatory properties over unhydrolyzed royal jelly protein. These findings suggest that RJP exerts protective effects on skin cells through antioxidative and anti-inflammatory mechanisms, indicating its promise for potential therapeutic avenues for managing oxidative stress and inflammation-related skin disorders.
RESUMO
The immune checkpoint blockade is an effective strategy to enhance the antitumor T cell effector activity, thus becoming one of the most promising immunotherapeutic strategies in the history of cancer treatment. Several immune checkpoint inhibitor have been approved by the FDA, such as antiCTLA4, antiPD1, antiPDL1 monoclonal antibodies. Most tumor patients benefitted from these antibodies, but some of the patients did not respond to them. To increase the effectiveness of immunotherapy, including immune checkpoint blockade therapies, miniaturization of antibodies has been introduced. A singledomain antibody, also known as nanobody, is an attractive reagent for immunotherapy and immunoimaging thanks to its unique structural characteristic consisting of a variable region of a single heavy chain antibody. This structure confers to the nanobody a light molecular weight, making it smaller than conventional antibodies, although remaining able to bind to a specific antigen. Therefore, this review summarizes the production of nanobodies targeting immune checkpoint molecules and the application of nanobodies targeting immune checkpoint molecules in immunotherapy and immunoimaging.
Assuntos
Antineoplásicos Imunológicos , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias , Anticorpos de Domínio Único , Animais , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Humanos , Inibidores de Checkpoint Imunológico/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/uso terapêuticoRESUMO
Mitochondria supply ATP essential for synaptic transmission. Neurons face exceptional challenges in maintaining energy homoeostasis at synapses. Regulation of mitochondrial trafficking and anchoring is critical for neurons to meet increased energy consumption during sustained synaptic activity. However, mechanisms recruiting and retaining presynaptic mitochondria in sensing synaptic ATP levels remain elusive. Here we reveal an energy signalling axis that controls presynaptic mitochondrial maintenance. Activity-induced presynaptic energy deficits can be rescued by recruiting mitochondria through the AMP-activated protein kinase (AMPK)-p21-activated kinase (PAK) energy signalling pathway. Synaptic activity induces AMPK activation within axonal compartments and AMPK-PAK signalling triggers phosphorylation of myosin VI, which drives mitochondrial recruitment and syntaphilin-mediated anchoring on presynaptic filamentous actin. This pathway maintains presynaptic energy supply and calcium clearance during intensive synaptic activity. Disrupting this signalling cross-talk triggers local energy deficits and intracellular calcium build-up, leading to impaired synaptic efficacy during trains of stimulation and reduced recovery from synaptic depression after prolonged synaptic activity. Our study reveals a mechanistic cross-talk between energy sensing and mitochondria anchoring to maintain presynaptic metabolism, thus fine-tuning short-term synaptic plasticity and prolonged synaptic efficacy.
Assuntos
Metabolismo Energético/fisiologia , Mitocôndrias/metabolismo , Receptor Cross-Talk/fisiologia , Sinapses/metabolismo , Sinapses/fisiologia , Proteínas Quinases Ativadas por AMP/metabolismo , Actinas/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Cálcio/metabolismo , Potenciais Pós-Sinápticos Excitadores , Feminino , Masculino , Potencial da Membrana Mitocondrial , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Cadeias Pesadas de Miosina/metabolismo , Proteínas do Tecido Nervoso/genética , Fosforilação , Cultura Primária de Células , Receptores Pré-Sinápticos/metabolismo , Quinases Ativadas por p21/metabolismoRESUMO
OBJECTIVE: To investigate the protective effect of ferulic acid on neuronal apoptosis of the spinal cord after aortic blood cross-clamping and its mechanism in rabbits. METHODS: Twenty-four rabbits were randomly divided into sham operation group, ischemia/reperfusion (I/R) injury group and ferulic acid group. Spinal cord I/R injury model was replicated by clamping blood of the infrarenal aorta for 40 minutes followed reperfusion for 7 days. Ferulic acid 50 mg/kg was injected 15 minutes before aortic clamping in ferulic acid group. The aorta was not clamped in sham operation group. Contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in plasma were assayed at 10 minutes before clamping (C-10), before removal of occlusion (C40), at 60 minutes (R60) and on the 7 th day (R7d) after reperfusion. Apoptosis of neurones of spinal cord and the expressions of Bax and Bcl-2 protein were assayed by immunohistochemical technique. Neurologic function score of hind limb was observed after operation. RESULTS: (1)The activity of MDA after I/R in I/R injury group was increased significantly compared with those before clamping and those in sham operation group (P<0.05 or P<0.01). The activity of MDA in ferulic acid group was significantly higher than that at C-10 (P<0.05), while significantly lower than those in I/R injury group at any time point (P<0.05 or P<0.01), but showed no significant difference compared with sham operation group. Changes in SOD activities were opposite to that of MDA. (2)The expression of Bax protein in I/R injury group was increased significantly (P<0.05), but the expression of Bcl-2 protein was decreased significantly compared with that in sham operation group (P<0.01). In ferulic acid group, the expression of Bax protein was significantly lower than that in I/R injury group and higher than that in sham operation group (P<0.01 and P<0.05), and the expression of Bcl-2 protein was higher than those in I/R injury group and sham operation group (both P<0.01). (3)The index of neuronal apoptosis in I/R injury group was significantly higher than that in sham operation group (P<0.01), and that in ferulic acid group was much lower than that in I/R injury group, but higher than sham operation group (P<0.01 and P<0.05). (4)The degree of paralysis in ferulic acid group was significantly lower than that in I/R injury group, and a higher neurologic score was observed (both P<0.01). CONCLUSION: Ferulic acid can reduce the spinal cord neuronal apoptosis as a result of aortic occlusion in rabbits. The possible mechanism is that it decreases protein expression of Bax, increases that of Bcl-2 and enhances antioxidation.
Assuntos
Apoptose/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Traumatismo por Reperfusão/patologia , Isquemia do Cordão Espinal/patologia , Animais , Aorta Abdominal/cirurgia , Constrição , Modelos Animais de Doenças , Masculino , Malondialdeído/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Coelhos , Distribuição Aleatória , Traumatismo por Reperfusão/metabolismo , Medula Espinal/metabolismo , Medula Espinal/patologia , Isquemia do Cordão Espinal/metabolismo , Superóxido Dismutase/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Encoding specificity theory predicts most effective recall by the original conditions at encoding, while generalization endows recall flexibly under circumstances which deviate from the originals. The CA1 regions have been implicated in memory and generalization but whether and which locally separated mechanisms are involved is not clear. We report here that fear memory is quickly formed, but generalization develops gradually over 24 h. Generalization but not fear memory is impaired by inhibiting ipsilateral (ips) or contralateral (con) CA1, and by optogenetic silencing of the ipsCA1 projections onto conCA1. By contrast, in vivo fEPSP recordings reveal that ipsCA1-conCA1 synaptic efficacy is increased with delay over 24 h when generalization is formed but it is unchanged if generalization is disrupted. Direct excitation of ipsCA1-conCA1 synapses using chemogenetic hM3Dq facilitates generalization formation. Thus, rapid generalization is an active process dependent on bilateral CA1 regions, and encoded by gradual synaptic learning in ipsCA1-conCA1 circuit.
Assuntos
Região CA1 Hipocampal/fisiologia , Condicionamento Psicológico/fisiologia , Medo/psicologia , Generalização Psicológica/fisiologia , Memória/fisiologia , Animais , Potenciação de Longa Duração/fisiologia , Masculino , Rememoração Mental/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Vias Neurais/fisiologia , Optogenética , Ratos , Ratos Sprague-Dawley , Sinapses/fisiologiaRESUMO
Early life stress increases risks of fear and anxiety related disorders in adulthood, which may be alleviated by fluoxetine treatment. However, the intergenerational impacts of maternal separation (MS) on fear and anxiety behaviors from father to their offspring are little known. And the potential effects of fluoxetine treatment on the intergenerational transmission have not been well tested. Here, we investigated whether fluoxetine can reverse the intergenerational effects of MS on fear and anxiety behaviors. The first generation (F1) male rats were exposed to MS 3 h daily from postnatal day 2-14 and then treated with fluoxetine for four weeks during adulthood before fear conditioning. We found that maternal separation significantly impaired contextual fear extinction in F1 adult male rats but not in their second generation (F2). Although no obvious effects of MS on anxiety were observed in F1 male rats, the F2 offspring displayed a phenotype of low anxiety-like behaviors despite they were reared in normal condition. Fluoxetine treatment in F1 males not only reversed the impairment of fear extinction in F1 males but also the low anxiety-like behaviors in their F2 offspring. These findings highlight the intergenerational impacts of early life stress on fear and anxiety behaviors, and provide a new sight of the intergenerational effect of fluoxetine therapy for early life stress related mental problems.
Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Ansiedade , Medo/efeitos dos fármacos , Fluoxetina/uso terapêutico , Privação Materna , Análise de Variância , Animais , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Ansiedade/genética , Condicionamento Clássico/efeitos dos fármacos , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Extinção Psicológica/efeitos dos fármacos , Medo/psicologia , Feminino , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
Early life stress increases the risk of posttraumatic stress disorders (PTSD). Patients with PTSD show impaired extinction of traumatic memory, and in women, this occurs more often when PTSD is preceded by child trauma. However, it is still unclear how early life stress accounts for extinction impairment. Here, we studied the effects of maternal separation (MS, postnatal day 2 to 14) on contextual fear extinction in adult female rats. Additionally, to examine changes in synaptic function affected by MS, we measured long-term potentiation (LTP) in prefrontal cortex and hippocampus in vitro, both of which have been implicated in fear extinction. We found that adult female rats had been subjected to MS exhibited significant spontaneous recovery of fear to the extinguished context. Furthermore, MS exposure resulted in LTP impairment in both infralimbic prefrontal cortex layer 2/3-layer 5 and hippocampal SC-CA1 pathways. Interestingly, no obvious effects of MS on contextual fear conditioning, fear recall as well as extinction training and recall were observed. Innate fear in the elevated plus maze or open field test remained nearly unaffected. These findings provided the first evidence that MS may exaggerate spontaneous recovery after contextual fear extinction, for which LTP impairment in the medial prefrontal cortex and hippocampus may be responsible, thereby possibly leading to impaired extinction associated with PTSD.
Assuntos
Condicionamento Psicológico/fisiologia , Extinção Psicológica/fisiologia , Medo/fisiologia , Hipocampo/fisiopatologia , Privação Materna , Córtex Pré-Frontal/fisiopatologia , Animais , Comportamento Exploratório/fisiologia , Feminino , Potenciação de Longa Duração/fisiologia , Aprendizagem em Labirinto/fisiologia , Rememoração Mental/fisiologia , Testes Neuropsicológicos , Ratos Sprague-Dawley , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Técnicas de Cultura de TecidosRESUMO
Foods contaminated with melamine potentially cause risk to human health. However, the neurotoxicity of melamine has not been adequately assessed. Here, we aimed to examine the effects of acute low-dose exposure to melamine on hippocampal synaptic plasticity and behaviors in rats. We found that bath application of 50-500µg/ml melamine decreased basal synaptic transmission in the Schaffer collateral-CA1 pathway of hippocampal slices from postnatal days (P) 10-14 rats in a concentration-dependent manner; furthermore, this decrease in transmission was related to the reduction of presynaptic function as indicated by the increased paired-pulse facilitation ratio. Rats at 2-3months old were less vulnerable to the effects of 500µg/ml melamine on basal synaptic transmission when compared with P10-14 and P21-28 rats. Melamine (50µg/ml) significantly impaired long-term potentiation (LTP), without affecting long-term depression (LTD), in both P10-14 and 2-3month-old rats. Oral treatment with melamine (5 and 25mg/kg) 1h before behavioral tests significantly decreased the immobility time of the forced swim test in 2-3month-old rats and had no effect on locomotor activity in the open field test in both P21-28 and 2-3month-old rats. Our findings reveal some of the aspects of neurotoxicity induced by acute low-dose of melamine in hippocampal synaptic plasticity and behavior.
Assuntos
Comportamento Animal/efeitos dos fármacos , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Triazinas/toxicidade , Animais , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To study the feasibility and authenticity of repairing alveolar defects in alveolar cleft patients with osteoinduction active material (OAM) in clinic. METHODS: Twenty-seven cases of alveolar defect chosen from clinic were divided into two groups (test group and control group). For test group (12 cases), OAM was transplanted to repair the alveolar cleft. For control group (15 cases), autogenous ilium cancellous bone were transplanted into the defect region to repair alveolar cleft. At 6 months after operation, CT and three-dimensional reconstruction were used to observe alveolar appearance, and the effect and clinical success rate of recover alveolar cleft by using different repair material were compared. RESULTS: In the 27 cases, all the maxillary continuity was restored except two of test group and two of control group. There was no significant difference between test group and control group regarding the clinical success rate of the alveolar cleft repair (P = 1.000). CONCLUSION: OAM was used to repair the alveolar cleft that can result in new bone formations and the burgeon of canines from the bone grafted areas. There is no significant difference between OAM and autogenous ilium cancellous bone regarding the effect of the alveolar cleft repair.
Assuntos
Processo Alveolar/patologia , Materiais Biocompatíveis/uso terapêutico , Transplante Ósseo , Fissura Palatina/cirurgia , Ílio/transplante , Processo Alveolar/cirurgia , Regeneração Óssea , HumanosRESUMO
OBJECTIVE: To assess the prevalence, demographic characteristics, risk factors and protective factors on major depression disorder (MDD) among the affected people in the epicenter, 7 months after the 2008-earthquake in Wenchuan, China. METHODS: Stratified multistage cluster randomization was conducted to choose 14 503 subjects aged 15 years or over in the city of Dujiangyan, Beichuan county and Qingchuan county, Sichuan province. We used the general health questionnaire (GHQ-12) as the screening instrument, and the structured clinical interview for DSM-IV-TR axis I disorder-patient edition (SCID-I/P) as the tool for diagnosis. RESULTS: There were 180 persons diagnosed as MDD with other 13 asymptomatic ones. The point prevalence of MDD was 1.27% and the lifetime prevalence was 1.36%. Risk factors were including:being female (OR = 1.56, 95%CI: 1.136 â¼ 2.143, P < 0.05), co-morbidity with somatic diseases (OR = 4.02, 95%CI: 2.75 - 5.90, P < 0.05), wounded in the earthquake (OR = 3.29, 95%CI: 1.92 - 5.65, P < 0.05), property loss up to 10 000 - 20 000 Yuan (OR = 2.09, 95%CI: 1.18 - 3.69, P < 0.05), property loss up to > 20 000 Yuan (OR = 2.54, 95% CI: 1.38 - 4.68, P < 0.05), death or missing of family members (OR = 3.79, 95%CI: 2.08 - 6.89, P < 0.05) and in middle-age (OR = 2.31, 95%CI: 1.38 - 3.86, P < 0.05) etc. Having had a job seemed to be a protective factor (OR = 0.60, 95%CI: 0.43 - 0.83, P < 0.05). CONCLUSION: Major depressive disorder appeared to be a common psychiatric disease in these quake-stricken areas, that causing serious problems. Sustained follow-up and care provided to the affected people in these areas were of extreme importance.