Qing Tian

Huazhong University of Science and Technology, Wu-han-shih, Hubei, China

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Publications (109)544.67 Total impact

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    ABSTRACT: Synaptic spine loss is one of the major preceding consequences of stroke damages, but its underlying molecular mechanisms remain unknown. Here, we report that a direct interaction of DAPK1 with Tau causes spine loss and subsequently neuronal death in a mouse model with stroke. We found that DAPK1 phosphorylates Tau protein at Ser262 (pS(262)) in cortical neurons of stroke mice. Either genetic deletion of DAPK1 kinase domain (KD) in mice (DAPK1-KD(-/-)) or blocking DAPK1-Tau interaction by systematic application of a membrane permeable peptide protects spine damages and improves neurological functions against stroke insults. Thus, disruption of DAPK1-Tau interaction is a promising strategy in clinical management of stroke. © The Author 2015. Published by Oxford University Press.
    Cerebral Cortex 05/2015; DOI:10.1093/cercor/bhv096 · 8.31 Impact Factor
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    ABSTRACT: Hydrogen-rich water (HRW) has anti-oxidant activities, and it exerts neuroprotective effects during ischemia-reperfusion brain injury. Parvalbumin and hippocalcin are two calcium buffering proteins, which are involved in neuronal differentiation, maturation and apoptosis. The aim of this study was to investigate whether HRW could moderate parvalbumin and hippocalcin expression during ischemic brain injury and glutamate toxicity-induced neuronal cell death. Focal brain ischemia was induced in male Sprague-Dawley rats by middle cerebral artery occlusion (MCAO). Rats were treated with H2O or HRW (6ml/kg per rat) before and after MCAO, and cerebral cortical tissues were collected 1, 7 and 14 days after MCAO. Based on our results, HRW treatment was able to reduce brain infarct volume and improve neurological function following ischemic brain injury. In addition, HRW prevented the ischemia-induced reduction of parvalbumin and hippocalcin levels in vivo and also reduced the glutamate toxicity-induced death of neurons, including the dose-dependent reduction of glutamate toxicity-associated proteins in vitro. Moreover, HRW attenuated the glutamate toxicity-induced elevate in intracellular Ca(2+) levels. All these results suggest that HRW could protect against ischemic brain injury and that the maintenance of parvalbumin and hippocalcin levels by HRW during ischemic brain injury might contribute to the neuroprotective effects against neuron damage. Copyright © 2015. Published by Elsevier B.V.
    Brain research 04/2015; 1615. DOI:10.1016/j.brainres.2015.04.038 · 2.83 Impact Factor
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    ABSTRACT: Endothelin1 (ET1) is a potent vasoconstrictor that is also known to be a neuropeptide that is involved in neural circuits. We examined the role of ET1 that has been implicated in the anxiogenic process. We found that infusing ET1 into the IL cortex increased anxiety-like behaviors. The ETA receptor (ETAR) antagonist (BQ123) but not the ETB receptor (ETBR) antagonist (BQ788) alleviated ET1-induced anxiety. ET1 had no effect on GABAergic neurotransmission or NMDA receptor (NMDAR)-mediated neurotransmission, but increased AMPA receptor (AMPAR)-mediated excitatory synaptic transmission. The changes in AMPAR-mediated excitatory postsynaptic currents were due to presynaptic mechanisms. Finally, we found that the AMPAR antagonists (CNQX) and BQ123 reversed ET1's anxiogenic effect, with parallel and corresponding electrophysiological changes. Moreover, infusing CNQX + BQ123 into the IL had no additional anxiolytic effect compared to CNQX treatment alone. Altogether, our findings establish a previously unknown anxiogenic action of ET1 in the IL cortex. AMPAR-mediated glutamatergic neurotransmission may underlie the mechanism of ET1-ETAR signaling pathway in the regulation of anxiety.
    Molecular Neurobiology 04/2015; DOI:10.1007/s12035-015-9163-9 · 5.29 Impact Factor
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    ABSTRACT: Endoplasmic reticulum (ER) stress has been indicated in the early stage of Alzheimer’s disease (AD), in which tau hyperphosphorylation is one major pathological alteration. The elevation of binding immunoglobulin protein (Bip), an important ER chaperon, was reported in AD brain. It is important to study the roles of ER-related chaperons in tau hyperphosphorylation. In this research, increased Bip was found in the brains of the AD model mice (Tg2576) compared to the age-matched control mice. Meanwhile, deficiency of SIL1, an important co-chaperon of Bip, was observed in brains of Tg2576 mice and in ER stress both in vivo and in vitro. Then, we transfected Bip-EGFP plasmid into HEK293 cells stably expressing the longest human tau (HEK293/tau) or N2a cells and found that increased Bip induced tau hyperphosphorylation via activating glycogen synthase kinase-3β (GSK-3β), an important tau kinase, and increased the association with tau and GSK-3β. When we overexpressed SIL1 in Bip-transfected HEK293/tau cells and thapsigargin-treated HEK293/tau cells, significantly reduced tau hyperphosphorylation and GSK-3β activation were observed. These results suggested the important roles of ER-related chaperons, Bip and SIL1, in AD-like tau hyperphosphorylation.
    Molecular Neurobiology 01/2015; DOI:10.1007/s12035-014-9039-4 · 5.29 Impact Factor
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    ABSTRACT: Estrogen deprivation is a high risk of cognitive dysfunction in neurodegenerative diseases, and the early used estrogen replacement has been proved effective in many studies. Because of the adverse actions, selective estrogen receptor modulating has been raised to substitute for estrogen replacement. In this study, we observed in hippocampus of bilaterally ovariectomized rats that the level of estrogen receptor α (ERα) was decreased in nuclei with activated glycogen synthase kinase-3β (GSK-3β) in cytoplasm at 8 weeks after operation. The level of nuclear ERα is important for its transcriptional property, and the inhibition of GSK-3β benefits to ERα nuclear translocation. Then, we used 4,4k,4a-(4-propyl-[1H]-pyrazole-1, 3, 5-triyl) trisphenol (PPT) (1 mg/kg/day), an agonist of ERα, combined with LiCl (40 mg/kg/day), an inhibitor of GSK-3β, to treat the ovariectomized rats. After the combination treatment of these two drugs (PPT + LiCl), the improved learning and memory abilities of ovariectomized rats in Morris water maze, increased dendritic spines in CA1 region, and decreased tau phosphorylation at Ser-396 in hippocampus were observed. Furthermore, PPT + LiCl treatment significantly increased ERα level in the nuclear fraction of hippocampus, and in the cytoplasmic fraction, the total level of GSK-3β was declined after treatment with its increased phosphorylation at Ser-9 (inactivation form). This study suggested that PPT + LiCl treatment could inhibit the activation of cytoplasmic GSK-3β and promote the nuclear translocation of ERα, and ERα together with GSK-3β maybe the targets to preserve hippocampus-dependent cognitive ability after long-term ovariectomy.
    Molecular Neurobiology 12/2014; DOI:10.1007/s12035-014-9050-9 · 5.29 Impact Factor
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    ABSTRACT: Cognition in all mammals including human beings declines during aging. The cellular events responsible for this decay involve a reduction of neurogenesis in the dentate gyrus. Here, we show that treatment with a nature product from a traditional Chinese medicine, namely salidroside restores the capacity of the dentate gyrus to generate new neurons and intercepts learning and memory decays in mice during aging. We uncover that new neurons in aging mice have functional features of an adult granule neuron by forming excitatory synapses with their putative targeting neurons. Genetic inhibition of synaptic transmission from new neurons abolishes the therapeutic effects of salidroside in behavioral tests. We also identify that salidroside targets CREB transcription for the survival of new neurons in the dentate gyrus of old mice. Thus, salidroside is therapeutically effective against learning and memory decays via stimulation of CREB-dependent functional neurogenesis in aging.
    Molecular Neurobiology 12/2014; DOI:10.1007/s12035-014-9045-6 · 5.29 Impact Factor
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    ABSTRACT: Background and Purpose-Death-associated protein kinase 1 (DAPK1) interacts with the tumor suppressor gene p53 via a direct binding of a death domain of DAPK1 to a DNA-binding motif (DM) of p53 (p53DM) and converges multiple cell death pathways in stroke. The goals of this study are to determine whether disruption of DAPK1-p53 interaction is therapeutically effective against stroke. Methods-We synthesized a membrane-permeable p53DM peptide (Tat-p53DM) and tested the therapeutic effects of Tat-p53DM in a mouse model with stroke. Results-We showed that Tat-p53DM blocked DAPK1-p53 interaction in brain cells in vivo. When administered 6 hours after stroke onset in adult male mice, Tat-p53DM was still therapeutically effective against brain damages and improved neurological functions. Conclusions-DAPK1-p53 interaction is a preferred target for therapeutic intervention of stroke.
    Stroke 08/2014; 45(10). DOI:10.1161/STROKEAHA.114.006348 · 6.02 Impact Factor
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    ABSTRACT: Alzheimer's disease (AD) is a common form of dementia. Early and differential diagnosis of AD has always been an arduous task for the medical expert due to the unapparent early symptoms and the currently imperfect imaging examination methods. Therefore, obtaining reliable markers with clinical diagnostic value in easily assembled samples is worthy and significant. Our previous work with laser Raman spectroscopy (LRS), in which we detected platelet samples of different ages of AD transgenic mice and non-transgenic controls, showed great effect in the diagnosis of AD. In addition, a multilayer perception network (MLP) classification method was adopted to discriminate the spectral data. However, there were disturbances, which were induced by noise from the machines and so on, in the data set; thus the MLP method had to be trained with large-scale data. In this paper, we aim to re-establish the classification models of early and advanced AD and the control group with fewer features, and apply some mechanism of noise reduction to improve the accuracy of models. An adaptive classification method based on the Gaussian process (GP) featured, with predictive probabilities, is proposed, which could tell when a data set is related to some kind of disease. Compared with MLP on the same feature set, GP showed much better performance in the experimental results. What is more, since the spectra of platelets are isolated from AD, GP has good expansibility and can be applied in diagnosis of many other similar diseases, such as Parkinson's disease (PD). Spectral data of 4 month and 12 month AD platelets, as well as control data, were collected. With predictive probabilities, the proposed GP classification method improved the diagnostic sensitivity to nearly 100%. Samples were also collected from PD platelets as classification and comparison to the 12 month AD. The presented approach and our experiments indicate that utilization of GP with predictive probabilities in platelet LRS detection analysis turns out to be more accurate for early and differential diagnosis of AD and has a wide application prospect.
    Laser Physics 08/2014; 24(8):085702. DOI:10.1088/1054-660X/24/8/085702 · 1.03 Impact Factor
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    Qing Tian, Qian Jiang
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    ABSTRACT: Alzheimer's disease (AD) has multiple etiopathogenic factors, yet the definitive cause remains unclear and the therapeutic strategies have been elusive. Combination therapy, as one of the promising treatments, has been studied for years and may exert synergistic beneficial effects on AD through polytherapeutic targets. In this study, we tested the effects of a synthesized juxtaposition (named SCR1693) composed of an acetylcholinesterase inhibitor (AChEI) and a calcium channel blocker (CCB) on the hyperhomocysteinemia (HHcy)-induced AD rat model, and found that SCR1693 remarkably improved the HHcy-induced memory deficits and preserved dendrite morphologies as well as spine density by upregulating synapse-associated proteins PSD95 and synapsin-1. In addition, SCR1693 attenuated HHcy-induced tau hyperphosphorylation at multiple AD-associated sites by regulating the activity of protein phosphatase-2A and glycogen synthase kinase-3β. Furthermore, SCR1693 was more effective than individual administration of both donepezil and nilvadipine which were used as AChEI and CCB, respectively, in the clinical practice. In conclusion, our data suggest that the polytherapeutic targeting juxtaposition SCR1693 (AChEI-CCB) is a promising therapeutic candidate for AD.
    Journal of Alzheimer's disease: JAD 07/2014; 42(3). DOI:10.3233/JAD-140597 · 3.61 Impact Factor
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    ABSTRACT: Hypoxia was shown to be associated with an increased risk of Alzheimer's disease (AD). The effects of hypoxia on the development of AD pathology and spatial memory ability and the possible molecular mechanisms remain poorly understood. In this study, we demonstrate that rats exposed to a hypoxic condition (10% oxygen concentration) for 1, 2, 4 and 8 weeks (6 h each day) displayed spatial memory impairment and increased tau phosphorylation at Ser198/199/202, Thr205, Ser262, Ser396 and Ser404 in the hippocampus. Concomitantly, the levels of Tyr216-phosphorylated glycogen synthase kinase (GSK)-3β (activated form of GSK-3β) and Tyr307-phosphorylated protein phosphatase 2A (inactivated form of PP2A) were significantly increased in the hippocampus of the rats with 1, 2, 4 and 8 weeks of hypoxia exposure, while the levels of methylated PP2A (activated form of PP2A) were significantly decreased in the hippocampus of the rats with 4 and 8 weeks of hypoxia exposure. In addition, the content of malondialdehyde, an indicator of oxidative stress, was elevated, whereas the activity of superoxide dismutase was not significantly changed in the hippocampus of the rats exposed to hypoxia. Taken together, these data demonstrated that hypoxia induced tau hyperphosphorylation and memory impairment in rats, and that the increased tau phosphorylation could be attributed to activation of GSK-3β and inactivation of PP2A. These data suggest that interventions to improve hypoxia may be helpful to prevent the development of AD pathology and cognitive impairment. © 2014 S. Karger AG, Basel.
    Neurodegenerative Diseases 06/2014; 14(3). DOI:10.1159/000362239 · 3.45 Impact Factor
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    ABSTRACT: Region-specific neurodegeneration was reported in brains of Alzheimer's disease (AD), but the mechanism is not fully understood. Here, we studied the expression of some AD-associated proteins in temporal cortex, frontal cortex, cerebellum, and hippocampus of 4-month-old male Sprague-Dawley rats. Levels of the phosphorylated tau at Thr231, Ser396, and Ser202/Thr205, phosphorylated amyloid-β protein precursor (AβPP) and amyloid-β, synapse-associated proteins glutamate receptors 2, N-methyl-D-aspartic receptors 1 (NR1), NR2A, NR2B, and postsynaptic density protein 95 were much lower in cerebellum, while the levels of total tau, phosphorylated tau at Thr205, Ser214, Ser262, and Ser198/199/202 epitopes, and total AβPP were similar in the four brain regions. As endoplasmic reticulum (ER) stress was reported in the early stage of AD, we injected tunicamycin, an ER stress inducer, into the lateral ventricular of rats and 48 hours later found in the other three brain regions but not cerebellum, increasing of binding immunoglobulin protein with the increased phosphorylation of pancreatic ER kinase, inositol-requiring enzyme 1, and activating transcription factor 6. Simultaneously, levels of phosphorylated tau at all of the above sites were significantly increased with the activation of glycogen synthase kinase-3β in temporal cortex, frontal cortex, and/or hippocampus, but not cerebellum. The synapse-associated proteins, GluR2, PSD95, and synapsin1, were found decreased in the hippocampus after tunicamycin exposure. These data together may partially explain why the AD-like neuropathology, such as formation of neurofibrillary tangles, was rarely detected in cerebellum.
    Journal of Alzheimer's disease: JAD 04/2014; 41(4). DOI:10.3233/JAD-140207 · 3.61 Impact Factor
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    ABSTRACT: Repeated electroconvulsive therapy (rECT) is widely applied in the treatment of refractory depression, one of whose side effects, memory impairment, is noticed and needs effective protection. In this reseach, by employing a recognized repeated electroconvulsive shock (rECS) rat model, we found that rECS induced significant spatial memory retention deficits with simultaneous decreases in long-term potential (LTP), enhanced excitable postsynaptic potentials (EPSP), population spike (PS) and input/output curve in perforant pathway-dentate gyrus (PP-DG), but no obvious neuron loss or dentritic spine loss in the brain by Nissle or Golgi stainings. Furthermore, the increased synaptic proteins of NR2A/B, PSD93, PSD95, the immediate early gene c-Fos and CREB protein were detected in hippocampus of rECS rats. rECS was also found to cause enhanced axon reorganization in DG region of hippocampus by Timm staining. Intraperitoneal injection of phenylbutyric acid (PBA), an aromatic short chain fatty acid, acting as a molecule chaperon, could prevent against rats from the rECS-induced memory deficits and synaptic potential enhancement by decreasing the levels of the abnormal increased memory-associated proteins and enhanced axon reorganization in hippocampus. Our data suggested that PBA may be potentially used for attenuating the rECS-induced memory impairment.
    Current neurovascular research 04/2014; DOI:10.2174/1567202611666140408115111 · 2.74 Impact Factor
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    ABSTRACT: MicroRNA-17-92 (miR-17-92) cluster has been demonstrated to play a crucial role in various human cancers. However, its effects in osteosarcoma have not yet been elucidated. The purpose of this study was to investigate the clinical significance of miR-17-92 cluster in osteosarcoma. MiR-17-92 cluster expression in osteosarcoma clinical samples and cell lines was detected by real-time quantitative RT-PCR. Then, the association of miR-17-92 cluster level with survival of osteosarcoma patients was performed by the Kaplan-Meier and Cox proportional regression analyses. Furthermore, the effects of miR-17-92 cluster on tumorigenicity of osteosarcoma cell lines were evaluated by in vitro assays. The relative expression of miR-17-92 cluster in osteosarcoma tissues was significantly higher than those in adjacent normal tissues (P=0.001). And there was a relationship between miR-17-92 cluster upregulation and advanced TNM stage of osteosarcoma patients (P=0.037). Moreover, higher miR-17-92 cluster expression clearly predicted poorer Recurrence-free survival (P<0.001) and Overall survival (P=0.002). In the multivariate analysis, high miR-17-92 cluster expression was an independent prognostic factor for Recurrence-free survival (P<0.001) and Overall survival (P=0.002). Furthermore, the cellular proliferation, invasion, and migration of osteosarcoma cell lines were significantly accelerated by miR-17-92 cluster plasmid in vitro assays.Our findings showed that miR-17-92 cluster could serve as a promising marker for tumor recurrence and survival of osteosarcoma patients. Moreover, miR-17-92 cluster has been identified as a promoter for tumorigenicity of osteosarcoma cells, thus it might be a critical targeted therapy strategy for osteosarcoma. Keywords: MiR-17-92 cluster, osteosarcoma, recurrence-free survival, overall survival, tumor progression, prognosis.
    Neoplasma 03/2014; 61(04). DOI:10.4149/neo_2014_056 · 1.64 Impact Factor
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    ABSTRACT: Background: Phospholipases A 2 (PLA 2) are ubiquitous enzymes involved in membrane fatty acid metabolism and intracellular signalling. Recent studies have shown that PLA 2 subtypes are implicated in the modulation of pathways related to memory acquisition and retrieval. Methods: We in-cluded 23 cognitively unimpaired older individuals were selected to this study divided in the experimental and control groups (EG and CG, respec-tively). The EG underwent a four-session memory training intervention and the CG completed the same evaluation as EG and received standard outpatient care only. Pre and pos-test measures included prose and list recall, WAIS-III digit symbol, strategy use measures, and PLA 2 group activity. The PLA 2 group activity was determined by radio-enzymatic assay. Results: After cognitive training, patients in the EG group had significant increase in cPLA 2 , sPLA 2 , total PLA 2 activity, and significant decrease in iPLA 2 activity (see table). Conclusions: Our results suggest that memory training may have a modulating effect on biological systems associated with cognitive functions and neurodegenerative diseases. Background: Alzheimer's disease (AD), the most common type of de-mentia in the elderly, is characterized by intracellular neurofibrillary tan-gles, cholinergic dysfunction and memory deficit. It has been reported that glycogen synthase kinase-3 (GSK-3) is the key kinase among protein kinases which can phosphorylate tau in the AD brain. We activated GSK-3 and induced a series of AD-like pathological alterations in rats by ventric-ular injection of Wortmannin (WT, PI3-K inhibitor) and GF-109203X (GFX, PKC inhibitor) at 24h-48h. It has been developed that GSK-3 may
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    ABSTRACT: Since abnormal post-translational modifications or gene mutations of tau have been detected in over twenty neurodegenerative disorders, tau has attracted widespread interest as a target protein. Among its various post-translational modifications, phosphorylation is the most extensively studied. It is recognized that tau hyperphosphorylation is the root cause of neurodegeneration in Alzheimer disease (AD); however, it is not clear how it causes neurodegeneration. Based on the findings that tau hyperphosphorylation leads to the escape of neurons from acute apoptosis and simultaneously impairs the function of neurons, we have proposed that the nature of AD neurodegeneration is the consequence of aborted apoptosis induced by tau phosphorylation. Therefore, proper manipulation of tau hyperphosphorylation could be promising for arresting AD neurodegeneration. In this review, the neuroprotective and neurodegenerative effects of tau hyperphosphorylation and our thoughts regarding their relationship are presented.
    Neuroscience Bulletin 03/2014; DOI:10.1007/s12264-013-1415-y · 1.83 Impact Factor
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    ABSTRACT: Automatic segmentation of the prostate zones has great potential of improving the accuracy of lesion detection during the image-guided prostate interventions. In this paper, we present a novel compact method to segment the prostate and its zones using multi-parametric magnetic resonance imaging (MRI) and the anatomical priors. The proposed method comprises of a prostate tissue representation using Gaussian mixture model (GMM), a prostate localization using the mean shift with the kernel of the prostate atlas and a prostate partition using the probabilistic valley between zones. The proposed method was tested on four sets of multi-parametric MRIs. The average Dice coefficient resulted from the segmentation of the prostate is 0.80 ± 0.03, the central zone 0.83 ± 0.04, and the peripheral zone 0.52 ± 0.09. The average computing time of the online segmentation is 1 min and 10 s per datasets on a PC with 2.4 GHz and 4.0 GB RAM. The proposed method is fast and has the potential to be used in clinical practices.
    SPIE Medical Imaging; 03/2014

Publication Stats

1k Citations
544.67 Total Impact Points

Institutions

  • 2004–2015
    • Huazhong University of Science and Technology
      • Department of Pathology and Pathophysiology
      Wu-han-shih, Hubei, China
  • 2009–2014
    • Tongji Medical University
      • Department of Pathophysiology
      Wu-han-shih, Hubei, China
  • 2007
    • Nanjing University
      • International Institute for Earth System Science
      Nan-ching, Jiangsu Sheng, China
  • 2005
    • Zhejiang University
      Hang-hsien, Zhejiang Sheng, China