Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 510
Filtrar
1.
Mikrochim Acta ; 187(12): 642, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33155077

RESUMO

A molecularly imprinted electrochemical sensor for the detection of serum amyloid A (MAA) in milk was established for early diagnosis of subclinical mastitis in dairy cows. The electrochemical sensor was initially constructed using a nanocomposite material (reduced graphene oxide/gold nanoparticles, AuNPs@rGO) to modify the working electrode. The template protein, MAA, was then immobilized using pyrrole as the functional monomer to carry out the electropolymerization. Finally, the template protein was removed to form a molecular imprint film with the capability to qualitatively and quantitatively signaling of MAA. Cyclic voltammetry (CV), differential pulse voltammetry (DPV), and scanning electron microscopy (SEM) were used to characterize the modification process of the molecularly imprinted electrochemical sensors. Under optimized conditions, the sensor shows two well-behaved linear relationships in the MAA concentration range 0.01 to 200 ng/mL. A lower detection limit was estimated to be 5 pg/mL (S/N = 3). Other parameters including the selectivity, reproducibility (RSD 3.2%), and recovery rate (96.1-103%) are all satisfactory. Compared with the traditional methods, detection of MAA to determine the subclinical mastitis of dairy cows can efficiently be diagnosed and hence prevent an outbreak of dairy cow mastitis. The electrochemical sensor can detect MAA more rapidly, sensitively, and inexpensively than the ELISA-based MAA detection. These advantages indicate that the method is promising for early diagnosis of dairy cows.

2.
Sci Signal ; 13(657)2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172955

RESUMO

The protein Dickkopf-1 (DKK1) is frequently overexpressed at the transcript level in hepatocellular carcinoma (HCC) and promotes metastatic progression through the induction of ß-catenin, a Wnt signaling effector. We investigated how DKK1 expression is induced in HCC and found that activation of the epidermal growth factor receptor (EGFR) promoted parallel MEK-ERK and PI3K-Akt pathway signaling that converged to epigenetically stimulate DKK1 transcription. In HCC cell lines stimulated with EGF, EGFR-activated ERK phosphorylated the kinase PKM2 at Ser37, which promoted its nuclear translocation. Also in these cells, EGFR-activated Akt phosphorylated the acetyltransferase p300 at Ser1834 Subsequently, PKM2 and p300 mediated the phosphorylation and acetylation, respectively, of histone H3 at the DKK1 promoter, which synergistically enhanced DKK1 transcription. The mechanism was supported with mutational analyses in cells and in a chemically induced HCC model in rats. The findings suggest that dual inhibition of the MEK and PI3K pathways might suppress the expression of DKK1 and, consequently, tumor metastasis in patients with HCC.

3.
BMC Ophthalmol ; 20(1): 459, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213408

RESUMO

BACKGROUND: To assess the corneal stress-strain index (SSI), which is a marker for material stiffness and corneal biomechanical parameters, in myopic eyes. METHODS: A total of 1054 myopic patients were included in this study. Corneal visualisation Scheimpflug technology was used to measure the SSI. Corneal biomechanics were assessed using the first and second applanation times (A1-and A2-times); maximum deflection amplitude (DefAmax); deflection area (HCDefArea); the highest concavity peak distance (HC-PD), time (HC-time), and deflection amplitude (HC-DefA); integrated radius (IR); whole eye movement (WEM); stiffness parameter (SP-A1;, biomechanically corrected intraocular pressure (BIOP); and Corvis biomechanical index (CBI). Scheimpflug tomography was used to obtain the mean keratometery (Km) and central corneal thickness (CCT). According to the spherical equivalent (SE) (low myopia: SE ≥ - 3.00D and high myopia: SE ≤ - 6.00D.), the suitable patients were divided into two groups. RESULTS: The mean SSI value was 0.854 ± 0.004. The SSI had a positive correlation with A1-time ((r = 0.272), HC-time (r = 0.218), WEM (r = 0.288), SP-A1 (r = 0.316), CBI (r = 0.199), CCT (r = 0.125), bIOP (r = 0.230), and SE (r = 0.313) (all p-values<0.01). The SSI had a negative correlation with HCDefA (r = - 0.721), HCDefArea (r = - 0.665), HC-PD(r = - 0.597), IR (r = - 0.555), DefAmax (r = - 0.564), and Km (r = - 0.103) (all p-values<0.01). There were significant differences in SSI (t = 8.960, p<0.01) and IR (t = - 3.509, p<0.01) between the low and high myopia groups. CONCLUSIONS: In different grades of myopia, the SSI values were lower in eyes with higher SEs. It indicates that the mechanical strength of the cornea may be compromised in high myopia. The SSI was positively correlated with the spherical equivalent, and it may provide a new way to study the mechanism of myopia.

4.
Neural Plast ; 2020: 8823111, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224190

RESUMO

High-frequency synchronization has been found in many real neural systems and is confirmed by excitatory/inhibitory (E/I) network models. However, the functional role played by it remains elusive. In this paper, it is found that high-frequency synchronization in E/I neuronal networks could improve the firing rate contrast of the whole network, no matter if the network is fully connected or randomly connected, with noise or without noise. It is also found that the global firing rate contrast enhancement can prevent the number of spikes of the neurons measured within the limited time window from being confused by noise, thereby enhancing the information encoding efficiency (quantified by entropy theory here) of the neuronal system. The mechanism of firing rate contrast enhancement is also investigated. Our work implies a possible functional role in information transmission of high-frequency synchronization in neuronal systems.

5.
Exp Eye Res ; : 108366, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33227296

RESUMO

Fungal keratitis is a serious corneal infection, which can lead to significant visual impairment and blindness. The cGAS-STING signaling pathway has emerged as a key player in innate immunity by sensing of invading pathogens. However, the role of the cGAS-STING pathway in Aspergillus fumigatus (A. fumigatus) keratitis is still unknown. In this study, we showed that the cGAS-STING signaling pathway was activated in human corneal epithelial cells (HCECs) and in mouse corneas infected with A. fumigatus. Knockdown of cGAS reduced A. fumigatus-induced production of pro-inflammatory cytokines, including TNF-α, IL-1ß, IL-6, and IFN-ß. However, reconstruction of cGAS activity restored the inflammatory response in HCECs infected with A. fumigatus. A specific cGAS inhibitor, RU.521, could also significantly inhibit A. fumigatus-induced inflammatory cytokine expression. In addition, we found that cGAS was indispensable for the autophagy flux evoked by A. fumigatus infection. Moreover, inhibition of cGAS using siRNA or RU.521 alleviated the severity of A. fumigatus keratitis in the mouse cornea. Therefore, the cGAS-STING signaling pathway contributes to the progression of A. fumigatus keratitis and targeting this pathway may provide therapeutic potential.

6.
Sleep ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175978

RESUMO

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is a frequent cause for consultation and a defining symptom of narcolepsy and idiopathic hypersomnia (IH). The associated mechanisms remain unclear. Lipocalin-type prostaglandin D synthase (LPGDS) is a plausible sleep-inducing candidate. This study is to compare cerebral spinal fluid (CSF) and serum LPGDS levels in patients group with hypersomnia of central origin, including those with narcolepsy type 1 (NT1) and type 2 (NT2) and IH, to those in healthy controls (Con). METHODS: Serum LPGDS, CSF LPGDS and CSF hypocretin-1(Hcrt-1) levels were measured by ELISA in 122 narcolepsy patients (106 NT1, and 16 NT2), 27 IH, and 51Con. RESULTS: LPGDS levels in CSF (p=0.02) and serum (p<0.001) were 22-25% lower in control subjects than in patients with EDS complaints, including NT1, NT2 and IH. In contrast to significant differences in CSF Hcrt-1 levels, CSF L-PGDS levels and serum L-PGDS were comparable among NT1, NT2 and IH (p>0.05), except for slightly lower serum LPGDS in IH than in NT1(p=0.01). Serum L-PGDS correlated modestly and negatively to sleep latency on MSLT(r=-0.227, p=0.007) in hypersomnia subjects. CONCLUSIONS: As a somnogen-producing enzyme, CSF/serum LPGDS may serve as a new biomarker for EDS of central origin and imply a common pathogenetic association, but would complement rather than replaces orexin markers.

7.
J Cell Physiol ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33184870

RESUMO

Cervical cancer is the fourth most frequent cancer in women worldwide. PDZ-binding kinase (PBK) is proven to promote the malignant behaviors of various carcinomas. However, its functional roles and oncogenic mechanisms in cervical cancer are poorly understood. In this study, we reported that PBK was highly expressed in cervical cancer tissues. PBK promoted the proliferation, metastasis, and cisplatin resistance of cervical cancer cells. OTS514, a specific PBK inhibitor, could significantly suppress proliferation and metastasis of cervical cancer cells in vitro and in a xenograft model. Besides, OTS514 could enhance cisplatin-based chemosensitivity in cervical cancer cells. Mechanistically, PBK promoted the expression and stabilization of c-Myc through phosphorylating ERK1/2. OTS514 suppressed the phosphorylation of ERK1/2 and the transcriptional activity of c-Myc. Furthermore, inhibition of the ERK signal pathway by U0126 reversed the increased proliferation and metastasis induced by overexpression of PBK. Exogenous expression of c-Myc counteracted the decreased proliferation and metastasis evoked by knockdown of PBK. In conclusion, PBK promoted the malignant progression of cervical cancer through ERK/c-Myc signal pathway. PBK might be a promising molecular target for cervical cancer treatment.

8.
Nanoscale ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33244546

RESUMO

We report a batch preparation of mm-scale 3D Ag hetero-nanoclusters which exhibit an excellent surface plasmon resonance ability via facile laser metallurgy. Under laser irradiation, the porous AgI-based coordination network crystals were instantly converted into 3D graphite-encapsulated Ag hetero-nanoclusters with uniform sizes and gaps in several seconds. The obtained hetero-nanoclusters exhibited superior 3D confocal laser energy utilization compared with the other 0D, 1D and 2D SERS substrates, solving the bottleneck caused by laser focusing deviation in the SERS active depth. The mass-produced SERS devices were ultra-sensitive for the detection of life and industrial organic pollutants in terms of low detection and enriched capacity.

9.
Shanghai Kou Qiang Yi Xue ; 29(4): 431-434, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-33089297

RESUMO

The announcement of National Health Commission on January 20, 2020 (No.1 of 2020) has included novel coronavirus pneumonia into the B class infectious diseases according to the law of the People's Republic of China on the prevention and control of infectious diseases, and has been managed as A class infectious diseases. People's governments at all levels and health administration departments have been paying high attention to it. With the alleviation of COVID-19 nationwide, dental clinics gradually resume to work. The main transmission routes of COVID-19 are respiratory droplets and contact transmission, hence oral radiological examination is kind of a high-risk operation. Standardized radiologic process is of great significance to reduce the risk of COVID-19 transmission. In accordance with the national and Shanghai epidemic prevention requirements, and in combination with the actual situation of various medical institutions, Oral and Maxillofacial Radiology Committee of Shanghai Stomatological Association formulated the expert consensus on standardized prevention and control of COVID-19 for clinical reference. This recommendation will be updated according to the situation of epidemic prevention and control in China and the new relevant diagnosis and treatment plans.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Radiografia Dentária , Betacoronavirus , China , Consenso , Humanos
10.
Artigo em Inglês | MEDLINE | ID: mdl-33108563

RESUMO

PURPOSE: Despite advances in the development of treatments for laryngeal cancer (LC), including surgical treatments and radio-chemotherapy, the survival rate of LC remains low. Therefore, novel metabolic signatures are urgently needed to evaluate the prognosis of LC patients. METHODS: Differentially expressed metabolic genes were extracted via bioinformatics analysis from the raw data of The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases. Univariate Cox regression and LASSO analyses were performed to identify metabolic genes that were significantly correlated with overall survival (OS). Using the Kaplan-Meier analysis and receiver operating characteristics, the prognostic power of candidate signatures was evaluated in the two databases. Gene Set Enrichment Analysis (GSEA) was performed to explore significant signaling pathways and underlying mechanisms in the high- and low-risk groups. RESULTS: Thirteen metabolism genes showed superior ability to predict OS for LC when compared to clinical variables, and patients in the high-risk group showed significantly poorer OS than those in the low-risk group. The area under the curve of receiver operating curves for 5- and 3-year OS was 0.929 and 0.899, respectively, which were better than the OS obtained with clinicopathological variables. Similar results obtained in the GEO cohort indicated that this gene signature could differentiate between LC patients with and without recurrence. CONCLUSION: To our knowledge, this study is the first to report that the 13 metabolic genes could serve as an independent biomarker for LC, which could provide vital prognostic information and prediction for personalized treatment of LC.

11.
Brain Imaging Behav ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033985

RESUMO

Primary dysmenorrhea (PDM) is a cyclic menstrual pain in the absence of pelvic anomalies, and women with PDM have an increased sensitivity to pain than the internal and external areas associated with menstrual pain. However, the brain abnormality in the ascending pain pathways in dysmenorrhea remains largely unclear. As the thalamus plays a significant role in transmission of nociceptive input, we examined whether white matter microstructure of the thalamus-related fiber tracts obtained by DTI in women with PDM (n = 47) differs from healthy controls. A novel tractography atlas-based analysis method that detects tract integrity and altered microstructural properties along selected fibers was employed. The fiber bundles of interest contained the thalamus- primary somatosensory cortex (SI), thalamus- dorsal anterior cingulate cortex (dACC)/supplementary motor area (SMA), thalamus-insula, and thalamus-ACC. As compared with controls, abnormal white matter microstructures were found along the thalamus-related white matter fiber tracts. Additionally, the intensity of menstrual pain was significantly associated with diffusion measures of thalamus-SI fiber connections. Our study suggested that the thalamus-related pain processing pathways had altered white matter integrity that persisted beyond the time of menstruation, and the white matter microstructure of the thalamus-SI pathways was closely related to menstrual pain in the intensity by women with PDM.

12.
Int J Med Sci ; 17(16): 2416-2426, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029084

RESUMO

Objective: To explore a way to reverse the drug resistance for irradiated CNE-1 human nasopharyngeal carcinoma cells and try to develop a new high efficacy with low toxicity therapeutic approach. Methods: 300 Gy irradiated the CNE-1 human nasopharyngeal carcinoma cells, and then treated with single-agent cisplatin or metformin, or combination of both drugs. MTT assay and FCM were applied to detect cell viability and apoptosis. Western blot and RT-PCR were used to characterize the protein and mRNA expression after various drug administrations. Results: The results presented single-agent metformin was capable of arresting the tumor growth and inducing apoptosis in irradiated CNE-1 cells and also demonstrated a synergy effect with cisplatin. Furthermore, metformin down-regulates the PECAM-1 expression, which could regulate Multi-drug Resistance-associate Proteins (MRPs) expression leading to cisplatin resistance of irradiated CNE-1 cells. A pan-MRP inhibitor, probenecid, can resecure cisplatin resistance leading by radiation. Conclusions: Metformin, due to its independent effects on PECAM-1, had a unique anti-proliferative effect on irradiated CNE-1 cells. It would be a new therapeutic option to conquer cisplatin resistance for advanced NPC patients after radiotherapy.

13.
J Perinat Med ; 48(9): 912-924, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33068387

RESUMO

Objectives To assess perinatal outcomes of COVID-19 infections during pregnancy and the possibility of vertical transmission. Methods An analysis was performed using Stata 15.0, and Q-test was used to evaluate the heterogeneity of the included studies. Results The most common symptoms were found to be fever (64.78%), cough (59.81%) and shortness of breath or dyspnea (23.86%). Of this 88.73% patients demonstrated typical COVID-19 signs on chest CT or X-ray. Intubation was carried out in 35.87% of patients, and 4.95% of mothers were admitted to the intensive care unit, where the rate of maternal death was <0.01% and that of premature delivery was 25.32%. The rate of the birth weight being <2,500 g was 30.65% and that of Neonatal intensive care unit (NICU) admission was 24.41%. Positive nasopharynx swabs or sputum from newborns was <0.01%. Conclusions Pregnant patients with COVID-19 most commonly presented with fever, cough, shortness of breath and dyspnea, most of which possessed imaging manifestations. The risk of intubation and admission to intensive care unit were high. The risk of premature delivery was higher, leading to a high risk of NICU admission and low neonatal birthweight. Vertical transmission of SARS-CoV-2 from mother to child was found to be unlikely.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez/epidemiologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/terapia , Cuidados Críticos/estatística & dados numéricos , Parto Obstétrico/métodos , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Terapia Intensiva Neonatal/estatística & dados numéricos , Intubação Intratraqueal/estatística & dados numéricos , Pandemias , Pneumonia Viral/terapia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/terapia , Nascimento Prematuro/epidemiologia
14.
Anal Chem ; 92(19): 13539-13549, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32924435

RESUMO

Here, it reports a high-throughput detection method for reliably quantitative analysis of illegal drugs in complex biological samples by means of a surface-enhanced Raman scattering (SERS) active microcavity and rapid pretreatment device. Based on the well-made hemispherical microcavities that regularly distributed on a glass array, the quality-controllable microcavity device is fabricated by the compact self-assembly of core-shell nanopeanuts (CSNPs) onto the inside surface. Both the CSNPs with a quantifiable internal standard signal of crystal violet acetate anchored inside their gap and the well-made microcavity referred to the physical amplification of the microscale groove surface will do well in trace analysis, which will allow us to realize the accurately quantitative SERS analysis of targeted analytes spread on the bottom area of the microcavity array. As an example, 0.8 nM malachite green and 160 ppb methamphetamine (MATM) have been successively detected in a wide range as standard, while even 0.01 ppm MATM mixed in the urine/serum samples has been efficiently tested by the microcavity device equipped with a rapid pretreatment device (manual monolithic column syringe needle). All of the above suggest that the SERS-active microcavity equipped with a rapid pretreatment device has potential in the on-site quick test of trace amounts of illegal drugs in bodily fluid samples or other field analysis of food sanitation, environmental safety, and public health.

15.
Mol Plant Microbe Interact ; : MPMI08200243R, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-32924759

RESUMO

A wide variety of leguminous plant-released (iso)flavonoids, such as genistein, are potential inducers of the nodulation (nod) genes of endosymbiotic rhizobia for the production of Nod factors, which are vital signaling molecules for triggering the symbiotic process. However, these (iso)flavonoids are generally thought to be toxic to the bacterial partner to varying degrees. Here, a novel TetR-like regulator gene of the soybean symbiont Bradyrhizobium diazoefficiens USDA110, bdtR (systematic designation blr7023), was characterized. It was found to be rapidly and preferentially induced by genistein, and its mutation resulted in significantly increased expression of the neighboring bll7019-bll7021 genes, encoding a multidrug resistance efflux pump system, in the absence of this isoflavonoid. Then, the transcriptional start site of BdtR was determined, and it was revealed that BdtR acted as a transcriptional repressor of the above efflux system through the binding of an AT-rich operator, which could be completely prevented by genistein. In addition, the ΔbdtR deletion mutant strain showed higher accumulation of extracellular genistein and became less susceptible to the isoflavonoid. In contrast, the inactivation of BdtR led to the significantly decreased induction of a nodulation gene (nodY) independent of the expression of nodD1 and nodW and to much weaker nodulation competitiveness. Taken together, the results show that BdtR plays an early sensing role in maintaining the intracellular homeostasis of genistein, helping to alleviate its toxic effect on this bacterium by negatively regulating neighboring genes encoding an efflux pump system while being essentially required for nodule occupancy competitiveness.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

16.
Biosci Trends ; 14(5): 376-383, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-32921695

RESUMO

The safety and feasibility of laparoscopic versus open liver resection (LLR vs. OLR) associated lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) are still controversial. The aim of the present study was to compare short and long-term outcomes. We reviewed data on 43 consecutive patients who underwent curative liver resection with associated lymphadenectomy for ICC. The short-term outcomes including postoperative morbidity and mortality, and the long-term outcomes including overall survival (OS) and recurrence-free survival (RFS) were compared. The median survival, 1- and 3-year OS in LLR and OLR groups were 22.5 months, 76.9% and 47.1%, and 12.1 months, 43.1% and 20.0%, respectively. The median survival, 1- and 3-year RFS in LLR and OLR groups were 10.3 months, 27.8% and 0%, and 8.1 months, 24.0% and 4.0%, respectively. The results showed that LLR obviously reduced intraoperative blood loss (median, 375 vs. 500ml, p = 0.016) and postoperative hospital stay (median, 6 vs. 9 days, p = 0.016). Moreover, there was no significant difference in short-term outcomes including postoperative morbidity (including wound infection, bile leakage, liver failure and pneumonia) and mortality within 30 days, and long-term outcomes including OS and RFS between LLR and OLR. (all p > 0.05). Multivariate analysis showed that CA19-9 level, TNM stage, and tumor differentiation were independent risk factors for OS and RFS. LLR for ICC is safety and feasibility compared with OLR. The advantage of LLR was to reduce intraoperative blood loss and postoperative hospital stay.

17.
Cereb Cortex ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32901273

RESUMO

Intermittent theta-burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation, is considered a potential therapy for treatment-resistant depression. The synaptic mechanism of iTBS has long been known to be an effective method to induce long-term potentiation (LTP)-like plasticity in humans. However, there is limited evidence as to whether the antidepressant effect of iTBS is associated with change in synaptic function in the prefrontal cortex (PFC) in preclinical study. Hence, we applied an antidepressant (i.e., fluoxetine)-resistant depression rat model induced by severe foot-shocks to investigate the antidepressant efficacy of iTBS in the synaptic pathology. The results showed that iTBS treatment improved not only the impaired LTP, but also the aberrant long-term depression in the PFC of antidepressant-resistant depression model rats. Moreover, the mechanism of LTP improvement by iTBS involved downstream molecules of brain-derived neurotrophic factor, while the mechanism of long-term depression improvement by iTBS involved downstream molecules of proBDNF. The aberrant spine morphology was also improved by iTBS treatment. This study demonstrated that the mechanism of the iTBS paradigm is complex and may regulate not only excitatory but also inhibitory synaptic effects in the PFC.

18.
Cell Mol Neurobiol ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32930942

RESUMO

Studies from postmortem and animal models have revealed altered synapse morphology and function in the brain of posttraumatic stress disorder (PTSD). And the effects of PTSD on dendrites and spines have been reported, however, the effection on axon include microtubule (MT) and synaptic vesicles of presynaptic elements remains unknown. Hippocampus is involved in abnormal memory in PTSD. In the present study, we used the single prolonged stress (SPS) model to mimic PTSD. Quantitative real-time polymerase chain reaction (RT-qPCR) and high-throughput sequencing (GSE153081) were utilized to analyze differentially expressed genes (DEGs) in the hippocampus of control and SPS rats. Immunofluorescence and western blotting were performed to examine change in axon-related proteins. Synaptic function was evaluated by measuring miniature excitatory postsynaptic currents (mEPSCs). RNA-sequencing analysis revealed 230 significantly DEGs between the control and SPS groups. Gene Ontology analysis revealed upregulation in axonemal assembly, MT formation, or movement, but downregulation in axon initial segment and synaptic vesicles fusion in the hippocampus of SPS rats. Increased expression in tau, ß-tubulin MAP1B, KIF9, CCDC40, DNAH12 and decreased expression in p-tau, stathmin suggested SPS induced axon extension. Increased protein expression in VAMP, STX1A, Munc18-1 and decreased expression in synaptotagmin-1 suggested SPS induced more SNARE complex formation but decreased ability in synaptic vesicle fusion to presynaptic active zone membrane in the hippocampus of SPS rats. Further, low mEPSC frequency in SPS rats indicated dysfunction in presynaptic membrane. These results suggest that axon extension and synaptic vesicles fusion abnormality are involved in dysfunction of PTSD.

20.
Mol Cell Neurosci ; 108: 103541, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32858150

RESUMO

The Single Prolonged Stress protocol is considered a model for PTSD, as it induces long lasting changes in rat behaviour and endocrine regulation. Previous work demonstrated that some of these changes can be prevented by treatment with the glucocorticoid receptor antagonist RU486, administered a week after the stressor. The current study evaluated the effects of an earlier intervention with RU486, as evaluated 1 week after SPS-exposure. Most RU486 effects occurred independent of prior stress, except for the reversal of a stress-induced increase in locomotor behaviour. The accompanying changes in gene expression depended on gene, brain region, and time. DNA methylation of the robustly down-regulated Fkbp5 gene was dissociated of changes in mRNA expression. The findings reinforce the long term effects of GR antagonist treatment, but also emphasize the need to evaluate changes over time to allow the identification of robust correlates between gene expression and behavioural/endocrine outcome of stressful experiences.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA