39 results on '"Youming Lu"'
Search Results
2. Social isolation reinforces aging-related behavioral inflexibility by promoting neuronal necroptosis in basolateral amygdala
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Juan Zhang, Dan Liu, Peng Fu, Zhi-Qiang Liu, Chuan Lai, Chun-Qing Yang, Kai Chen, Wen-Dai Bao, Fan Hu, Hui-Yun Du, Weili Yang, Jie Wang, Heng-Ye Man, Youming Lu, and Ling-Qiang Zhu
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Neurons ,Mice ,Aging ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Social Isolation ,Basolateral Nuclear Complex ,Necroptosis ,Animals ,Molecular Biology - Abstract
Aging is characterized with a progressive decline in many cognitive functions, including behavioral flexibility, an important ability to respond appropriately to changing environmental contingencies. However, the underlying mechanisms of impaired behavioral flexibility in aging are not clear. In this study, we reported that necroptosis-induced reduction of neuronal activity in the basolateral amygdala (BLA) plays an important role in behavioral inflexibility in 5-month-old mice of the senescence-accelerated mice prone-8 (SAMP8) line, a well-established model with age-related phenotypes. Application of Nec-1s, a specific inhibitor of necroptosis, reversed the impairment of behavioral flexibility in SAMP8 mice. We further observed that the loss of glycogen synthase kinase 3α (GSK-3α) was strongly correlated with necroptosis in the BLA of aged mice and the amygdala of aged cynomolgus monkeys (Macaca fascicularis). Moreover, genetic deletion or knockdown of GSK-3α led to the activation of necroptosis and impaired behavioral flexibility in wild-type mice, while the restoration of GSK-3α expression in the BLA arrested necroptosis and behavioral inflexibility in aged mice. We further observed that GSK-3α loss resulted in the activation of mTORC1 signaling to promote RIPK3-dependent necroptosis. Importantly, we discovered that social isolation, a prevalent phenomenon in aged people, facilitated necroptosis and behavioral inflexibility in 4-month-old SAMP8 mice. Overall, our study not only revealed the molecular mechanisms of the dysfunction of behavioral flexibility in aged people but also identified a critical lifestyle risk factor and a possible intervention strategy.
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- 2022
3. Correction: Synaptic dysfunction of Aldh1a1 neurons in the ventral tegmental area causes impulsive behaviors
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Xinyan Li, Wenting Chen, Xian Huang, Wei Jing, Tongmei Zhang, Quntao Yu, Hongyan Yu, Hao Li, Qing Tian, Yumei Ding, and Youming Lu
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Cellular and Molecular Neuroscience ,Neurology (clinical) ,Molecular Biology - Published
- 2023
4. LINC00662 Promotes Proliferation and Invasion and Inhibits Apoptosis of Glioma Cells Through miR-483-3p/SOX3 Axis
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Lei Yuan, Pengqi Zhang, Youming Lu, Aijun Zhang, and Xin Chen
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Carcinogenesis ,SOXB1 Transcription Factors ,Apoptosis ,Bioengineering ,Glioma ,General Medicine ,Applied Microbiology and Biotechnology ,Biochemistry ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Cell Movement ,Cell Line, Tumor ,Humans ,RNA, Long Noncoding ,Molecular Biology ,Cell Proliferation ,Biotechnology - Abstract
LINC00662 plays a prominent role in the carcinogenesis and progression of diverse cancers. However, its biological functions in glioma are still unclear. LINC00662 expression in glioma tissue samples and cell lines was examined by quantitative real-time polymerase chain reaction. The correlation between LINC00662 expression and the clinical characteristics of 50 patients with glioma was analyzed. LINC00662 knockdown and overexpression cell lines were constructed, and the effects of LINC00662 on the proliferation, invasion, and apoptosis of glioma cells were evaluated by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, Transwell, and flow cytometry assays, respectively. Besides, the relationships among LINC00662, miR-483-3p, and sex-determining region Y-box 3 (SOX3) were assessed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Western blot was used to detect the regulatory effects of LINC00662 and miR-483-3p on SOX3 expression in glioma cells. LINC00662 expression level was elevated in glioma tissues and cell lines compared to that in normal tissues and cell lines. LINC00662 high expression was associated with the adverse prognosis of patients with glioma. Knockdown of LINC00662 repressed the proliferation and invasion of glioma cells, and promoted apoptosis. Additionally, it was revealed that LINC00662 acted as the molecular sponge of miR-483-3p, and SOX3 was verified as a direct target of miR-483-3p. The inhibition of miR-483-3p expression and SOX3 overexpression reversed the biological effects of LINC00662 knockdown on glioma cells. This study reports the key regulatory role of LINC00662/miR-483-3p/SOX3 axis in the tumorigenesis and progression of glioma, bringing novel insights into the underlying mechanisms of glioma.
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- 2022
5. Chk1 Inhibition Ameliorates Alzheimer’s Disease Pathogenesis and Cognitive Dysfunction Through CIP2A/PP2A Signaling
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Wenting Hu, Zhuoqun Wang, Huiliang Zhang, Yacoubou Abdoul Razak Mahaman, Fang Huang, Dongli Meng, Ying Zhou, Shiyi Wang, Nan Jiang, Jing Xiong, Jukka Westermarck, Youming Lu, Jianzhi Wang, Xiaochuan Wang, Yangping Shentu, and Rong Liu
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Pharmacology ,Amyloid beta-Peptides ,Intracellular Signaling Peptides and Proteins ,Membrane Proteins ,Mice, Transgenic ,Neurodegenerative Diseases ,tau Proteins ,Autoantigens ,environment and public health ,Disease Models, Animal ,Mice ,enzymes and coenzymes (carbohydrates) ,Alzheimer Disease ,Checkpoint Kinase 1 ,Animals ,Humans ,Cognitive Dysfunction ,Pharmacology (medical) ,Protein Phosphatase 2 ,Neurology (clinical) ,Phosphorylation ,biological phenomena, cell phenomena, and immunity ,Signal Transduction - Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative disease with limited therapeutic strategies. Cell cycle checkpoint protein kinase 1 (Chk1) is a Ser/Thr protein kinase which is activated in response to DNA damage, the latter which is an early event in AD. However, whether DNA damage-induced Chk1 activation participates in the development of AD and Chk1 inhibition ameliorates AD-like pathogenesis remain unclarified. Here, we demonstrate that Chk1 activity and the levels of protein phosphatase 2A (PP2A) inhibitory protein CIP2A are elevated in AD human brains, APP/PS1 transgenic mice, and primary neurons with Aβ treatment. Chk1 overexpression induces CIP2A upregulation, PP2A inhibition, tau and APP hyperphosphorylation, synaptic impairments, and cognitive memory deficit in mice. Moreover, Chk1 inhibitor (GDC0575) effectively increases PP2A activity, decreases tau phosphorylation, and inhibits Aβ overproduction in AD cell models. GDC0575 also reverses AD-like cognitive deficits and prevents neuron loss and synaptic impairments in APP/PS1 mice. In conclusion, our study uncovers a mechanism by which DNA damage-induced Chk1 activation promotes CIP2A-mediated tau and APP hyperphosphorylation and cognitive dysfunction in Alzheimer’s disease and highlights the therapeutic potential of Chk1 inhibitors in AD.
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- 2022
6. Fabrication of high-performance ZnO-based thin-film transistors by Mg/H co-doping at room temperature
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Zongjin Jiang, Dongbo Yin, Deliang Zhu, Wangying Xu, Shun Han, Ming Fang, Wenjun Liu, Peijiang Cao, Xinke Liu, and Youming Lu
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Electrical and Electronic Engineering ,Condensed Matter Physics ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials - Published
- 2022
7. Ultra-high sensitive and ultra-low NO2 detection at low-temperature based on ultrathin In2O3 nanosheets
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Zeng Yuxiang, Deliang Zhu, Xinke Liu, Dnyandeo Pawar, Wenjun Liu, Peijiang Cao, Ch. N. Rao, YongZhi Cai, Ming Fang, Shun Han, RongGuan Chen, Youming Lu, and WangYin Xu
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Detection limit ,Materials science ,Oxide ,chemistry.chemical_element ,Repeatability ,Condensed Matter Physics ,Oxygen ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials ,chemistry.chemical_compound ,chemistry ,Chemical engineering ,Phase (matter) ,Nitrogen dioxide ,Electrical and Electronic Engineering ,Selectivity ,Indium - Abstract
In this study, the high oxygen vacancy-rich ultrathin indium oxide (In2O3) nanosheets are synthesized by low-cost and environmental-friendly solvothermal method. The gas sensing properties of In2O3 nanosheets to low concentration of nitrogen dioxide (NO2) (concentration in 5 ppb to 5 ppm) at 50 °C are investigated. All In2O3 samples are successfully characterized using various techniques to obtain the information related to phase, morphological, oxygen vacancies, and surface area, etc. It is observed that among all the samples, the In2O3-350 exhibited benchmarked response of around 3223 at 2 ppm NO2 gas, with theoretical detection limit down to ppb level. The sensor has shown superior sensing characteristics, such as wide sensing bandwidth, excellent selectivity, high long-term stability, and good repeatability. It is considered that the high oxygen deficiency present on In2O3 nanosheets acts as favorable reaction sites for such remarkable sensing performance, and therefore, these improved gas-sensing properties make the In2O3 nanosheets suitable to detect NO2 at low-temperature.
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- 2021
8. Identification of an endogenous glutamatergic transmitter system controlling excitability and conductivity of atrial cardiomyocytes
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Li Li, Hongyu Liu, Yi-Han Chen, Qicheng Zou, Jian Yang, Youming Lu, Xingdong Gu, Ke Xiong, Qiang Ji, Luying Peng, Dandan Liang, Jinfeng Xue, Lingling Wang, Xiaoyu He, Duanyang Xie, Luxin Wang, Xuling Su, Yi Liu, Guanghua Wang, and Xueting Gao
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Induced Pluripotent Stem Cells ,Action Potentials ,Endogeny ,030204 cardiovascular system & hematology ,Article ,03 medical and health sciences ,Glutamatergic ,0302 clinical medicine ,Atrial Fibrillation ,Animals ,Humans ,Myocytes, Cardiac ,Heart Atria ,GRIA3 ,Induced pluripotent stem cell ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,biology ,Glutamate receptor ,Cell Biology ,Rats ,Cell biology ,Electrophysiology ,cardiovascular system ,biology.protein ,Excitatory postsynaptic potential ,Ionotropic effect - Abstract
As an excitatory transmitter system, the glutamatergic transmitter system controls excitability and conductivity of neurons. Since both cardiomyocytes and neurons are excitable cells, we hypothesized that cardiomyocytes may also be regulated by a similar system. Here, we have demonstrated that atrial cardiomyocytes have an intrinsic glutamatergic transmitter system, which regulates the generation and propagation of action potentials. First, there are abundant vesicles containing glutamate beneath the plasma membrane of rat atrial cardiomyocytes. Second, rat atrial cardiomyocytes express key elements of the glutamatergic transmitter system, such as the glutamate metabolic enzyme, ionotropic glutamate receptors (iGluRs), and glutamate transporters. Third, iGluR agonists evoke iGluR-gated currents and decrease the threshold of electrical excitability in rat atrial cardiomyocytes. Fourth, iGluR antagonists strikingly attenuate the conduction velocity of electrical impulses in rat atrial myocardium both in vitro and in vivo. Knockdown of GRIA3 or GRIN1, two highly expressed iGluR subtypes in atria, drastically decreased the excitatory firing rate and slowed down the electrical conduction velocity in cultured human induced pluripotent stem cell (iPSC)-derived atrial cardiomyocyte monolayers. Finally, iGluR antagonists effectively prevent and terminate atrial fibrillation in a rat isolated heart model. In addition, the key elements of the glutamatergic transmitter system are also present and show electrophysiological functions in human atrial cardiomyocytes. In conclusion, our data reveal an intrinsic glutamatergic transmitter system directly modulating excitability and conductivity of atrial cardiomyocytes through controlling iGluR-gated currents. Manipulation of this system may open potential new avenues for therapeutic intervention of cardiac arrhythmias.
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- 2021
9. PINK1-mediated Drp1S616 phosphorylation modulates synaptic development and plasticity via promoting mitochondrial fission
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Qingtao Gao, Runyi Tian, Hailong Han, Jesse Slone, Caifang Wang, Xiao Ke, Tongmei Zhang, Xiangyu Li, Yuhong He, Panlin Liao, Fang Wang, Ye Chen, Shiqing Fu, Kexuan Zhang, Fangfang Zeng, Yingxuan Yang, Zhuo Li, Jieqiong Tan, Jiada Li, Youming Lu, Taosheng Huang, Zhonghua Hu, and Zhuohua Zhang
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Cancer Research ,Genetics - Abstract
Dynamic change of mitochondrial morphology and distribution along neuronal branches are essential for neural circuitry formation and synaptic efficacy. However, the underlying mechanism remains elusive. We show here that Pink1 knockout (KO) mice display defective dendritic spine maturation, reduced axonal synaptic vesicles, abnormal synaptic connection, and attenuated long-term synaptic potentiation (LTP). Drp1 activation via S616 phosphorylation rescues deficits of spine maturation in Pink1 KO neurons. Notably, mice harboring a knockin (KI) phosphor-null Drp1S616A recapitulate spine immaturity and synaptic abnormality identified in Pink1 KO mice. Chemical LTP (cLTP) induces Drp1S616 phosphorylation in a PINK1-dependent manner. Moreover, phosphor-mimetic Drp1S616D restores reduced dendritic spine localization of mitochondria in Pink1 KO neurons. Together, this study provides the first in vivo evidence of functional regulation of Drp1 by phosphorylation and suggests that PINK1-Drp1S616 phosphorylation coupling is essential for convergence between mitochondrial dynamics and neural circuitry formation and refinement.
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- 2022
10. Ag Localized Surface Plasma-Modulated NBE Emissions from ZnCdO Thin Films
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Peijiang Cao, Wenjun Liu, Youming Lu, Shaobing Wu, Shun Han, Zeng Yuxiang, Deliang Zhu, Wangying Xu, Xi Cheng, and Ming Fang
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010302 applied physics ,Photoluminescence ,Materials science ,business.industry ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Evaporation (deposition) ,Electronic, Optical and Magnetic Materials ,law.invention ,Pulsed laser deposition ,Semiconductor ,law ,0103 physical sciences ,Materials Chemistry ,Optoelectronics ,Quantum efficiency ,Electrical and Electronic Engineering ,Thin film ,0210 nano-technology ,business ,Localized surface plasmon ,Light-emitting diode - Abstract
Recently, metal surface plasma technology has been widely used to improve the quantum efficiency of optoelectronic devices, such as ZnO light-emitting diodes (LEDs). In this work, Ag films with the appropriate thickness were prepared by evaporation and annealed, and a layer of ZnCdO films with different Cd concentrations was grown on the Ag films by the pulsed laser deposition method. During this process, the changes in the Cd concentrations caused the near-band edge (NBE) emission of the ZnCdO films to be continuously adjusted in the ultraviolet to green wavelength range by controlling the oxygen pressure. The prepared Ag nanoparticles and ZnCdO composite films were used to study the metal localized surface plasmon (LSP) effect. The results show that the enhanced or reduced photoluminescence intensity of ZnCdO NBE depends on the probability of electrons transport to either the LSP level or the Fermi level of the metal. This discovery provides an important theoretical basis for the preparation of ZnCdO semiconductor LEDs in the future.
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- 2020
11. Electroluminescence Properties of a Zinc Oxide Nanorod Array Heterojunction Light-Emitting Diode
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Shun Han, Zeng Yuxiang, Deliang Zhu, Wangying Xu, Hua Jiang, Youming Lu, Ming Fang, Peijiang Cao, Wenjun Liu, and Ximing Rong
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010302 applied physics ,Materials science ,Valence (chemistry) ,business.industry ,Heterojunction ,02 engineering and technology ,Electroluminescence ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Electronic, Optical and Magnetic Materials ,Pulsed laser deposition ,law.invention ,law ,0103 physical sciences ,Materials Chemistry ,Optoelectronics ,Nanorod ,Electrical and Electronic Engineering ,0210 nano-technology ,business ,Excitation ,Diode ,Light-emitting diode - Abstract
A p-GaN/i-MgO/n-ZnO nanorod array (NRA) heterojunction light-emitting diode has been fabricated. Its room-temperature electroluminescence spectra under different forward biases revealed a strong emission band across the whole visible region, which was blue-shifted when increasing the forward bias. The origin of this visible emission is considered to be related to oxygen vacancy (VO) defects in different valence states, where the blue emission (∼ 460 nm) comes from neutral oxygen vacancy (VOX ) defects and the green emission (∼ 520 nm) from singly charged oxygen vacancy (VO+ ) defects, while the yellow (∼ 580 nm) and red emission (∼ 670 nm) are attributed to doubly charge oxygen vacancy (VO++ ) defects. These VO defects in different states can convert into one another under different excitation conditions, resulting in the blue-shift of the emission peak as the forward voltage is increased.
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- 2020
12. Temperature-Dependent Crystallization of Ga2O3 for Ultraviolet Photodetectors
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Zeng Yuxiang, Deliang Zhu, Ximing Rong, Jinjie Wu, Youming Lu, Peijiang Cao, Wenjun Liu, Shun Han, and Chao Li
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010302 applied physics ,Materials science ,business.industry ,Scanning electron microscope ,Band gap ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Electronic, Optical and Magnetic Materials ,law.invention ,Pulsed laser deposition ,Amorphous solid ,Absorption edge ,law ,0103 physical sciences ,Materials Chemistry ,Optoelectronics ,Electrical and Electronic Engineering ,Crystallization ,Thin film ,0210 nano-technology ,business ,Dark current - Abstract
As an n-type oxide semiconductor, Ga2O3 shows great promise in solar-blind ultraviolet (UV) photodetectors due to its adequate band gap, high absorption coefficient, high thermal and chemical stability, high breakdown voltage, and high sensitivity to UV light. In order to investigate the photoresponse of the Ga2O3 photodetector with different crystallization status, we fabricated a series of β-Ga2O3 thin films on a sapphire substrate via pulsed laser deposition with different deposition temperatures from 250°C to 650°C. X-ray diffraction and scanning electron microscopy result showed crystallization enhancement due to the increasing of deposition temperature, and the crystallization procedure started at ∼ 450°C. Optical analysis indicated a blue shift present at the absorption edge (from 4.6 eV to 5.1 eV) with temperature increasing from 450°C to 650°C, showing modulation feasibility in the band gap due to temperature dependence. In addition, all samples showed high transmittance (over 90%) over the entire visible spectrum. Film detectors fabricated by these samples showed high photoresponse and high light/dark current ratio (ILight/IDark) on Ga2O3 deposited at 450°C. Transmission electron microscopy result for film deposited at 450°C showed that the top and bottom regions of films contained both amorphous and crystalline Ga2O3, while there was no crystallization in the middle area of the film, indicating that a combined amorphous-crystalline Ga2O3 film with adequate ratio of crystalline state can significantly enhance the photoresponse while restraining the dark current.
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- 2020
13. Synaptic dysfunction of Aldh1a1 neurons in the ventral tegmental area causes impulsive behaviors
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Xian Huang, Youming Lu, Yumei Ding, Tongmei Zhang, Hao Li, Quntao Yu, Qing Tian, Wei Jing, Xinyan Li, Wenting Chen, and Hongyan Yu
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Male ,Glutamate decarboxylase ,Delay of gratification ,Neurotransmission ,Biology ,Inhibitory postsynaptic potential ,Synaptic Transmission ,Mice ,Cellular and Molecular Neuroscience ,Postsynaptic potential ,medicine ,Animals ,RC346-429 ,Molecular Biology ,Aldh1a1 neurons ,Neurons ,Ventral Tegmental Area ,Synaptic circuits ,RC952-954.6 ,Glutamate receptor ,Long-term potentiation ,Ventral tegmental area ,Impulsive behaviors ,medicine.anatomical_structure ,Geriatrics ,Impulsive Behavior ,Synapses ,Excitatory postsynaptic potential ,Neurology. Diseases of the nervous system ,Neurology (clinical) ,Alzheimer’s disease ,Neuroscience ,Research Article - Abstract
Background Aldh1a1 neurons are a subtype of gamma-aminobutyric acid (GABA) inhibitory neurons that use Aldh1a1 rather than glutamate decarboxylase (GAD) as an enzyme for synthesizing GABA transmitters. However, the behaviors and circuits of this newly identified subtype of inhibitory interneurons remain unknown. Methods We generated a mutant mouse line in which cyclization recombination enzyme (CRE) was expressed under the control of the Aldh1a1 promotor (Aldh1a1-CRE mice). Using this mutant strain of mice together with the heterozygous male Alzheimer’s disease (AD) related model mice (APPswe/PSEN1dE9, or AD mice) and a genetically modified retrograde and anterograde synaptic tracing strategy, we have studied a specific synaptic circuit of Aldh1a1 neurons with system-level function and disease progression in AD mice. Results We demonstrate that Aldh1a1 neurons encode delay of gratification that measures self-control skills in decision making by projecting inhibitory synapses directly onto excitatory glutamate neurons in the intermediate lateral septum (EGNIS) and receiving synaptic inputs from layer 5b pyramidal neurons in the medial prefrontal cortex (L5PN). L5PN → Aldh1a1 synaptic transmission undergoes long-term potentiation (LTP). Pathway specific inhibition by either genetic silencing presynaptic terminals or antagonizing postsynaptic receptors impairs delay of gratification, resulting in the impulsive behaviors. Further studies show that reconstitution of Aldh1a1-deficient neurons with the expression of exogenous Aldh1a1 (eAldh1a1) restores Aldh1a1 → EGNIS synaptic transmission and rescues the impulsive behaviors in AD mice. Conclusions These results not only identify a specific function and circuit of Aldh1a1 neurons but also provide a cellular point of entry to an important but understudied synaptic mechanism for the induction of impulsive behaviors at an early stage of AD.
- Published
- 2021
14. The mechanism of Annexin A1 to modulate TRPV1 and nociception in dorsal root ganglion neurons
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Dian Yu, You Shang, Yao Yi, Youming Lu, Yufen Zhang, Hongyan Yu, Xiao Ke, Lei Pei, Qiang Li, and Sehui Ma
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QH301-705.5 ,TRPV1 ,QD415-436 ,Pharmacology ,Biochemistry ,General Biochemistry, Genetics and Molecular Biology ,Formyl peptide receptor 2 ,chemistry.chemical_compound ,Formyl peptide receptor ,Dorsal root ganglion ,medicine ,Patch clamp ,Biology (General) ,Hot plate test ,Receptor ,Annexin A1 ,Neuronal sensitivity ,Chemistry ,Research ,Transient receptor potential vanilloid 1 ,medicine.anatomical_structure ,Nociception ,Capsaicin ,Nociceptive sensation ,TP248.13-248.65 ,Biotechnology - Abstract
Background Annexin A1 (ANXA1) exerts anti-nociceptive effect through ANXA1 receptor formyl peptide receptor 2 (FPR2/ALX (receptor for lipoxin A4), FPR2) at the dorsal root ganglia (DRG) level. However, the mechanisms remain elucidated. By using radiant heat, hot/cold plate, tail flick, von Frey, and Randall-Selitto tests to detect nociception in intact and chemical (capsaicin, menthol, mustard oil, formalin or CFA) injected AnxA1 conditional knockout (AnxA1−/−) mice, applying calcium imaging and patch clamp recordings in cultured DRG neurons to measure neuronal excitability, conducting immunofluorescence and western blotting to detect the protein levels of TRPV1, FPR2 and its downstream molecules, and performing double immunofluorescence and co-immunoprecipitation to investigate the interaction between Calmodulin (CaM) and TRPV1; we aim to uncover the molecular and cellular mechanisms of ANXA1’s role in antinociception. Results AnxA1−/− mice exhibited significant sensitivity to noxious heat (mean ± SD, 6.2 ± 1.0 s vs. 9.9 ± 1.6 s in Hargreaves test; 13.6 ± 1.5 s vs. 19.0 ± 1.9 s in hot plate test; n = 8; P vs. 76.2 ± 10.9; n = 8; P vs. 76.0 ± 21.9 s; n = 8; P vs. 320.4 ± 33.6 s; n = 8; P vs. 5.9 ± 1.4 s; n = 8; P 2+ response, TRPV1 currents and neuronal firing in AnxA1 deficient DRG neurons. Furthermore, ANXA1 mimic peptide Ac2-26 robustly increased intracellular Ca2+, inhibited TRPV1 current, activated PLCβ and promoted CaM-TRPV1 interaction. And these effects of Ac2-26 could be attenuated by FPR2 antagonist Boc2. Conclusions Selective deletion of AnxA1 in DRG neurons enhances TRPV1 sensitivity and deteriorates noxious heat or capsaicin induced nociception, while ANXA1 mimic peptide Ac2-26 desensitizes TRPV1 via FPR2 and the downstream PLCβ-Ca2+-CaM signal. This study may provide possible target for developing new analgesic drugs in inflammatory pain.
- Published
- 2021
15. ZnO UV Photodetectors Modified by Ag Nanoparticles Using All-Inkjet-Printing
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Youming Lu, Changshi Lao, Zhangwei Chen, Xinke Liu, Zhichao Yang, Hsiang-Chun Wang, Youhua Zhu, and Yuehua Hong
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Materials science ,Photoluminescence ,Passivation ,Nanochemistry ,Photodetector ,Surface plasmons ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,X-ray photoelectron spectroscopy ,lcsh:TA401-492 ,General Materials Science ,Photocurrent ,Nano Express ,Ag nanoparticles ,business.industry ,Surface plasmon ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Ray ,0104 chemical sciences ,Inkjet printing ,ZnO photodetector ,Optoelectronics ,lcsh:Materials of engineering and construction. Mechanics of materials ,0210 nano-technology ,business - Abstract
To further improve the performance of all-inkjet-printing ZnO UV photodetector and maintain the advantages of inkjet printing technology, the inkjet printing Ag nanoparticles (NPs) were deposited on the inkjet printing ZnO UV photodetector for the first time. The inkjet printing Ag NPs can passivate the surface defects of ZnO and work as surface plasmons from the characterization of photoluminescence (PL), X-ray photoelectron spectroscopy (XPS), and finite difference time domain method (FDTD) simulation. The normalized detectivity (D*) of the Ag NP-modified detector reaches to 1.45 × 1010 Jones at 0.715 mW incident light power, which is higher than that of 5.72 × 109 Jones of the bare ZnO photodetector. The power-law relationship between the photocurrent and the incident light power of the Ag NP-modified ZnO detector is Ipc ∝ P2.34, which means the photocurrent is highly sensitive to the change of incident light power.
- Published
- 2020
16. Degradation of Caytaxin Causes Learning and Memory Deficits via Activation of DAPK1 in Aging
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Lei Pei, Manfei Deng, Yu Guo, Xiao Ke, Youming Lu, Xiaoan Zhang, Zhuoze Wu, Hao Li, Henok Kessete Afewerky, and You Cai
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Male ,0301 basic medicine ,Aging ,Small interfering RNA ,Neuroscience (miscellaneous) ,Hippocampus ,Nerve Tissue Proteins ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Memory ,Animals ,Gene silencing ,Gene Silencing ,Protein kinase A ,Neurons ,Memory Disorders ,Caspase 3 ,Chemistry ,Cell biology ,Enzyme Activation ,Mice, Inbred C57BL ,Death-Associated Protein Kinases ,030104 developmental biology ,Neurology ,Protein kinase domain ,Proteolysis ,030217 neurology & neurosurgery ,Degradation (telecommunications) - Abstract
Loss of memory is an inevitable clinic sign in aging, but its underlying mechanisms remain unclear. Here we show that death-associated protein kinase (DAPK1) is involved in the decays of learning and memory in aging via degradation of Caytaxin, a brain-specific member of BNIP-2. DAPK1 becomes activated in the hippocampus of mice during aging. Activation of DAPK1 is closely associated with degradation of Caytaxin protein. Silencing Caytaxin by the expression of small interfering RNA (siRNA) that targets specifically to Caytaxin in the hippocampus of adult mice impairs the learning and memory. Genetic inactivation of DAPK1 by deletion of DAPK1 kinase domain prevents the degradation of Caytaxin and protects against learning and memory declines. Thus, activation of DAPK1 impairs learning and memory by degrading Caytaxin during aging.
- Published
- 2018
17. Expression of BC1 Impairs Spatial Learning and Memory in Alzheimer’s Disease Via APP Translation
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Ling-Qiang Zhu, Na Tang, Tongmei Zhang, Lei Pei, Hao Li, Youming Lu, Jian Wang, Zemin Fang, Shu Shu, Wenting Chen, Lin Wang, Qing Tian, Yu Guo, Houze Zhu, Pei Pang, Xin Yang, Tian Tian, Dan Liu, Xinyan Li, and Jianhua Wu
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0301 basic medicine ,medicine.medical_specialty ,Neurology ,Spatial Learning ,Neuroscience (miscellaneous) ,Mice, Transgenic ,Disease ,Amyloid beta-Protein Precursor ,Fragile X Mental Retardation Protein ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Alzheimer Disease ,Memory ,medicine ,Amyloid precursor protein ,Animals ,RNA, Messenger ,Memory Disorders ,biology ,Translation (biology) ,medicine.disease ,Long non-coding RNA ,Mice, Inbred C57BL ,Fragile X syndrome ,030104 developmental biology ,Protein Biosynthesis ,Excitatory postsynaptic potential ,biology.protein ,Spatial learning ,RNA, Long Noncoding ,Neuroscience - Abstract
Aggregation of amyloid-β (Aβ) peptides, which are the cleavage products of amyloid precursor protein (APP), is a major pathological hallmark in the brain of Alzheimer's disease (AD). Now, we know little about the roles of APP translation in the disease progression of AD. Here, we show that BC1, a long noncoding RNA (lncRNA), is expressed in the brain of AD mice. BC1 induces APP mRNA translation via association with a fragile X syndrome protein (FMRP). Inhibition of BC1 or BC1-FMRP association in AD mice blocks aggregation of Aβ in the brain and protects against the spatial learning and memory deficits. Expression of exogenous BC1 in excitatory pyramidal neurons of mice induces Aβ peptides accumulation and the spatial learning and memory impairments. This study provides a novel mechanism underlying aggregation of Aβ peptides via BC1 induction of APP mRNA translation and hence warrants a promising target for AD therapy.
- Published
- 2017
18. Tau-mediated iron export prevents ferroptotic damage after ischemic stroke
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Laila C. Roisman, Scott Ayton, Xiu-Lian Wang, Jian-Zhi Wang, Roberto Cappai, Youming Lu, Rong Liu, Huan Xiong, Peng Lei, Zhen-Yu Liuyang, Qing-Zhang Tuo, Paul A. Adlard, Ashley I. Bush, Li Xl, Lei Pei, Peter J. Crouch, Katherine Ganio, Qiang Wang, Zhang St, and Katherine A Jackman
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0301 basic medicine ,medicine.medical_specialty ,Brain ischemia ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,medicine.artery ,Internal medicine ,mental disorders ,medicine ,Amyloid precursor protein ,Artery occlusion ,Molecular Biology ,Stroke ,biology ,business.industry ,Neurotoxicity ,medicine.disease ,Psychiatry and Mental health ,030104 developmental biology ,Endocrinology ,Middle cerebral artery ,Toxicity ,biology.protein ,business ,Reperfusion injury ,030217 neurology & neurosurgery - Abstract
Functional failure of tau contributes to age-dependent, iron-mediated neurotoxicity, and as iron accumulates in ischemic stroke tissue, we hypothesized that tau failure may exaggerate ischemia-reperfusion-related toxicity. Indeed, unilateral, transient middle cerebral artery occlusion (MCAO) suppressed hemispheric tau and increased iron levels in young (3-month-old) mice and rats. Wild-type mice were protected by iron-targeted interventions: ceruloplasmin and amyloid precursor protein ectodomain, as well as ferroptosis inhibitors. At this age, tau-knockout mice did not express elevated brain iron and were protected against hemispheric reperfusion injury following MCAO, indicating that tau suppression may prevent ferroptosis. However, the accelerated age-dependent brain iron accumulation that occurs in tau-knockout mice at 12 months of age negated the protective benefit of tau suppression against MCAO-induced focal cerebral ischemia-reperfusion injury. The protective benefit of tau knockout was revived in older mice by iron-targeting interventions. These findings introduce tau-iron interaction as a pleiotropic modulator of ferroptosis and ischemic stroke outcome.
- Published
- 2017
19. Altered neurogenesis and disrupted expression of synaptic proteins in prefrontal cortex of SHANK3-deficient non-human primate
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Hui Zhao, Weili Yang, Youming Lu, Yinghui Zheng, Yong Q. Zhang, Yong-hui Jiang, Zhuchi Tu, Xiangyu Guo, Jiezhao Zheng, Sen Yan, Xiao-Jiang Li, Huijuan Xu, Huanhuan Yan, Rui Tian, and Zhujun Li
- Subjects
0301 basic medicine ,Non human primate ,biology ,Autism Spectrum Disorder ,Neurogenesis ,Prefrontal Cortex ,Nerve Tissue Proteins ,Cell Biology ,Disease Models, Animal ,Macaca fascicularis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Expression (architecture) ,biology.animal ,Synapses ,Animals ,Primate ,CRISPR-Cas Systems ,Prefrontal cortex ,Letter to the Editor ,Molecular Biology ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Altered neurogenesis and disrupted expression of synaptic proteins in prefrontal cortex of SHANK3 -deficient non-human primate
- Published
- 2017
20. Genetic Mutation of GluN2B Protects Brain Cells Against Stroke Damages
- Author
-
Shu Shu, Huanhuan Yan, Lei Pei, Na Tang, Yan Shi, Jianhua Wu, Youming Lu, Yu Guo, Houze Zhu, Honglin Yan, and You Cai
- Subjects
Male ,0301 basic medicine ,Mutant ,Neuroscience (miscellaneous) ,Stimulation ,AMPA receptor ,Biology ,medicine.disease_cause ,Receptors, N-Methyl-D-Aspartate ,Synaptic Transmission ,Neuroprotection ,Brain Ischemia ,Mice, Neurologic Mutants ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,medicine ,Animals ,Receptor ,Neurons ,Mutation ,Behavior, Animal ,Glutamate receptor ,Brain ,Cell biology ,Mice, Inbred C57BL ,Stroke ,Death-Associated Protein Kinases ,030104 developmental biology ,Neurology ,NMDA receptor ,Calcium ,Ion Channel Gating ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Immediately following ischemia, glutamate accumulates in the extracellular space and results in extensive stimulation of its receptors including N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors. A large amount of Ca2+ influx directly through the receptor-gated ion channels which leads to Ca2+ overload and triggers several downstream lethal reactions. As a result, cell dies via apoptosis or necrosis, or both. Death-associated protein kinase 1 (DAPK1) physically and functionally interacts with the NMDA receptor GluN2B subunit at extra-synaptic sites and this interaction acts as a central mediator for stroke damage. The goal of this study is to explore an effective strategy in the treatment of stroke with a molecular genetic manipulation to interrupt DAPK1-GluN2B interaction. We generated a mutant strain of mice with the conditional deletion of GluN2B C-terminal tail consisting of amino acids 886-1269 in the forebrain excitatory neurons (the GluN2B mutant mice) and tested the protective effects of this mutation in stroke damages. GluN2B mutation effectively disrupted the DAPK1-GluN2B interaction and inhibited extra-synaptic NMDA receptor currents without affecting synaptic NMDA receptor channel activity in the central neurons. GluN2B mutation protected against stroke damages both in vitro and in vivo and hence improved behavioral performance. Disruption of the DAPK1-GluN2B interaction is therapeutically effective against stroke damages.
- Published
- 2017
21. A circuit view of deep brain stimulation in Alzheimer’s disease and the possible mechanisms
- Author
-
Yunyun Han, Xiaodan Yang, Youming Lu, Danfang Yu, Jun Zhou, and Huanhuan Yan
- Subjects
0301 basic medicine ,Fornix ,medicine.medical_specialty ,Deep brain stimulation ,Neurology ,Movement disorders ,medicine.medical_treatment ,Review ,Disease ,lcsh:Geriatrics ,lcsh:RC346-429 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Cognition ,0302 clinical medicine ,Alzheimer Disease ,Memory ,Nucleus basalis of Meynert ,medicine ,Animals ,Humans ,Vertical limb of diagonal band ,Molecular Biology ,lcsh:Neurology. Diseases of the nervous system ,Entorhinal cortex ,business.industry ,Neurodegeneration ,Brain ,medicine.disease ,lcsh:RC952-954.6 ,030104 developmental biology ,nervous system ,Neurology (clinical) ,medicine.symptom ,Cognition Disorders ,business ,Alzheimer’s disease ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Alzheimer’s disease (AD) is characterized by chronic progressive cognitive deterioration frequently accompanied by psychopathological symptoms, including changes in personality and social isolation, which severely reduce quality of life. Currently, no viable therapies or present-day drugs developed for the treatment of AD symptoms are able to slow or reverse AD progression or prevent the advance of neurodegeneration. As such, non-drug alternatives are currently being tested, including deep brain stimulation (DBS). DBS is an established therapy for several neurological and psychiatric indications, such as movement disorders. Studies assessing DBS for other disorders have also found improvements in cognitive function, providing the impetus for clinical trials on DBS for AD. Targets of DBS in AD clinical trials and animal model studies include the fornix, entorhinal cortex (EC), nucleus basalis of Meynert (NBM), and vertical limb of diagonal band (VDB). However, there is still no comprehensive theory explaining the effects of DBS on AD symptoms or a consensus on which targets provide optimal benefits. This article reviews the anatomy of memory circuits related to AD, as well as studies on DBS rescue of AD in these circuits and the possible therapeutic mechanisms.
- Published
- 2019
22. Author Correction: A novel pathway regulates social hierarchy via lncRNA AtLAS and postsynaptic synapsin IIb
- Author
-
Ling-Qiang Zhu, Youming Lu, Man-Fei Deng, Mei Ma, Xian Huang, Wan Xiong, Dan Liu, Heng-Ye Man, and Fan Hu
- Subjects
Postsynaptic potential ,Atlas (topology) ,Social hierarchy ,Cell Biology ,Synapsin ,Biology ,Molecular Biology ,Neuroscience - Published
- 2021
23. Cnga2 Knockout Mice Display Alzheimer’s-Like Behavior Abnormities and Pathological Changes
- Author
-
Youming Lu, Enjie Liu, Ke Li, He-Zhou Huang, Jian-Zhi Wang, Ling-Qiang Zhu, Ao-Ji Xie, and Yu Hu
- Subjects
0301 basic medicine ,Tau hyperphosphorylation ,medicine.medical_specialty ,Neurology ,Neuroscience (miscellaneous) ,Cyclic Nucleotide-Gated Cation Channels ,tau Proteins ,Dendrite ,Hippocampus ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Alzheimer Disease ,Parenchyma ,Avoidance Learning ,medicine ,Animals ,Maze Learning ,Pathological ,Mice, Knockout ,Memory Disorders ,Amyloid beta-Peptides ,Neurodegeneration ,medicine.disease ,Olfactory Bulb ,030104 developmental biology ,medicine.anatomical_structure ,Knockout mouse ,Alpha-2 adrenergic receptor ,Psychology ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Olfactory dysfunction is recognized as a potential risk factor for Alzheimer's disease (AD). We have reported previously that olfactory deprivation by olfactory bulbectomy (OBX) induced Alzheimer's-like pathological changes and behavioral abnormalities. However, the acute OBX model undergoes surgical-induced brain parenchyma loss and unexpected massive hemorrhage so that it cannot fully mimic the progressive olfactory loss and neurodegeneration in AD. Here, we employed the mice loss of cyclic nucleotide-gated channel alpha 2 (Cnga2) which is critical for olfactory sensory transduction, to investigate the role of olfactory dysfunction in AD pathological process. We found that impaired learning and memory abilities, loss of dendrite spines, as well as decrement of synaptic proteins were displayed in Cnga2 knockout mice. Moreover, Aβ overproduction, tau hyperphosphorylation, and somatodendritic translocation were also found in Cnga2 knockout mice. Our findings suggest that progressive olfactory loss leads to Alzheimer's-like behavior abnormities and pathological changes.
- Published
- 2015
24. Infralimbic Endothelin1 Is Critical for the Modulation of Anxiety-Like Behaviors
- Author
-
Chengye Yao, Yan Shi, Na Tang, Houze Zhu, Huanhuan Yan, Shan Wang, Huijuan Jin, You Cai, Yu Guo, Jianhua Wu, Youming Lu, Ling-Qiang Zhu, Lei Pei, Hao Li, Lin-Lin Bi, Meng-meng Xu, Qing Tian, Na Li, Na Wei, Ming Chen, Xin Yang, Shu Shu, and Honglin Yan
- Subjects
Male ,0301 basic medicine ,medicine.drug_class ,Infralimbic cortex ,Neuroscience (miscellaneous) ,Glutamic Acid ,AMPA receptor ,Anxiety ,Neurotransmission ,Peptides, Cyclic ,Synaptic Transmission ,Anxiolytic ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Limbic System ,medicine ,Animals ,Receptors, AMPA ,6-Cyano-7-nitroquinoxaline-2,3-dione ,Neurons ,Behavior, Animal ,Endothelin-1 ,Receptors, Endothelin ,Chemistry ,musculoskeletal, neural, and ocular physiology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Neurology ,Anxiogenic ,cardiovascular system ,CNQX ,Excitatory postsynaptic potential ,NMDA receptor ,Neuroscience ,030217 neurology & neurosurgery - 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 ET(A) receptor (ET(A)R) antagonist (BQ123) but not the ET(B) receptor (ET(B)R) 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-ET(A)R signaling pathway in the regulation of anxiety.
- Published
- 2015
25. Therapeutic Intervention of Learning and Memory Decays by Salidroside Stimulation of Neurogenesis in Aging
- Author
-
Shan Wang, Huijuan Jin, Youming Lu, Chengye Yao, Lei Pei, Yan Wu, Tianhua Yan, Xiaogang Shu, Qing Tian, Dan Liu, Honglin Yan, Na Wei, Xin Yang, and Lin Wang
- Subjects
Male ,0301 basic medicine ,Aging ,medicine.medical_specialty ,Neurology ,Cell Survival ,Neurogenesis ,Green Fluorescent Proteins ,Neuroscience (miscellaneous) ,Cell Count ,Stimulation ,Neurotransmission ,CREB ,Synaptic Transmission ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Glucosides ,Neural Stem Cells ,Phenols ,medicine ,Animals ,Learning ,Cyclic AMP Response Element-Binding Protein ,Spatial Memory ,Neurons ,Memory Disorders ,Neuronal Plasticity ,biology ,Dentate gyrus ,Salidroside ,Cell Differentiation ,Rats ,Mice, Inbred C57BL ,030104 developmental biology ,nervous system ,chemistry ,Dentate Gyrus ,Synapses ,Excitatory postsynaptic potential ,biology.protein ,Psychology ,Neuroscience - 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.
- Published
- 2014
26. Erratum to: The Lesion Analysis of Cholinergic Neurons in 5XFAD Mouse Model in the Three-Dimensional Level of Whole Brain
- Author
-
Lei Pei, Hao Li, Youming Lu, K A Henok, Huanhuan Yan, Zuoze Wu, Yunyun Han, Pei Pang, Wenqi Chen, Kai Pan, Houze Zhu, Tongmei Zhang, Xiao Ke, and Jianhua Wu
- Subjects
0301 basic medicine ,Genetically modified mouse ,Basal forebrain ,Cholinergic Fibers ,Neuroscience (miscellaneous) ,Hippocampus ,Biology ,Amygdala ,Lesion ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Neurology ,medicine ,Cholinergic ,Cholinergic neuron ,medicine.symptom ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Cholinergic system is very important for many higher brain functions, including learning and memory. Cholinergic neurons, especially those in the basal forebrain, are specifically susceptible in some neurodegenerative diseases, such as in Alzheimer’s disease (AD). Here, we studied the cholinergic system lesion effects of five familial AD mutations in 5XFAD mice, a transgenic mouse model of AD. Although the cholinergic system has been studied in this mouse model, the cholinergic deficits in AD mice have never been systematically mapped in a whole-brain three-dimensional (3D) reconstruction. Using the 3D reconstruction technology combined with immunohistochemistry (3D-IHC) and design-based stereology, we comprehensively compared the differences of the cholinergic neurons and fibers between the 5XFAD mice and C57BL/6 control mice at different age. Here, we found that the lesion of cholinergic fibers occurred earlier than the cholinergic neuron loss in 5XFAD mice. The cholinergic fiber lesions in the AD mice started sequentially in amygdala, cortex, hippocampus, and then basal forebrain. However, the basal forebrain was the first brain region observed with cholinergic neuron loss at the age of 9 months in 5XFAD mice, whereas such phenomenon first occurred at the age of 15 months in C57BL/6 control mice. Moreover, using 3D reconstruction to compare the lesion of cholinergic system of aged 5XFAD and C57BL/6 control mice, it is intuitive to notice the pathologic regions and severity of lesion. Therefore, the 3D-IHC provides detailed overview of the cholinergic neurons in the whole mouse brain, which will contribute to the study of the developing and pathologic mouse brain.
- Published
- 2017
27. The Lesion Analysis of Cholinergic Neurons in 5XFAD Mouse Model in the Three-Dimensional Level of Whole Brain
- Author
-
Huanhuan Yan, Pei Pang, Wenqi Chen, Houze Zhu, null Henok K.A., Hao Li, Zuoze Wu, Xiao Ke, Jianhua Wu, Tongmei Zhang, Kai Pan, Lei Pei, Yunyun Han, and Youming Lu
- Subjects
0301 basic medicine ,Aging ,Neuroscience (miscellaneous) ,Brain ,Mice, Transgenic ,Cholinergic Neurons ,Mice, Inbred C57BL ,Disease Models, Animal ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Imaging, Three-Dimensional ,030104 developmental biology ,0302 clinical medicine ,Neurology ,Alzheimer Disease ,Animals ,030217 neurology & neurosurgery - Abstract
Cholinergic system is very important for many higher brain functions, including learning and memory. Cholinergic neurons, especially those in the basal forebrain, are specifically susceptible in some neurodegenerative diseases, such as in Alzheimer's disease (AD). Here, we studied the cholinergic system lesion effects of five familial AD mutations in 5XFAD mice, a transgenic mouse model of AD. Although the cholinergic system has been studied in this mouse model, the cholinergic deficits in AD mice have never been systematically mapped in a whole-brain three-dimensional (3D) reconstruction. Using the 3D reconstruction technology combined with immunohistochemistry (3D-IHC) and design-based stereology, we comprehensively compared the differences of the cholinergic neurons and fibers between the 5XFAD mice and C57BL/6 control mice at different age. Here, we found that the lesion of cholinergic fibers occurred earlier than the cholinergic neuron loss in 5XFAD mice. The cholinergic fiber lesions in the AD mice started sequentially in amygdala, cortex, hippocampus, and then basal forebrain. However, the basal forebrain was the first brain region observed with cholinergic neuron loss at the age of 9 months in 5XFAD mice, whereas such phenomenon first occurred at the age of 15 months in C57BL/6 control mice. Moreover, using 3D reconstruction to compare the lesion of cholinergic system of aged 5XFAD and C57BL/6 control mice, it is intuitive to notice the pathologic regions and severity of lesion. Therefore, the 3D-IHC provides detailed overview of the cholinergic neurons in the whole mouse brain, which will contribute to the study of the developing and pathologic mouse brain.
- Published
- 2017
28. β-Amyloid triggers aberrant over-scaling of homeostatic synaptic plasticity
- Author
-
James Gilbert, Youming Lu, Ling-Qiang Zhu, Heng-Ye Man, Shu Shu, and Xin Yang
- Subjects
0301 basic medicine ,Synaptic scaling ,Amyloid beta ,musculoskeletal, neural, and ocular physiology ,Nonsynaptic plasticity ,AMPA receptor ,Biology ,Pathology and Forensic Medicine ,Cell biology ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,030104 developmental biology ,0302 clinical medicine ,Synaptic fatigue ,nervous system ,Homeostatic plasticity ,Synaptic plasticity ,Metaplasticity ,biology.protein ,Neurology (clinical) ,Neuroscience ,030217 neurology & neurosurgery - Abstract
The over-production of β-amyloid (Aβ) has been strongly correlated to neuronal dysfunction and altered synaptic plasticity in Alzheimer’s disease (AD). Accordingly, it has been proposed that disrupted synaptic transmission and neuronal network instability underlie memory failure that is evident in the early phases of AD. Homeostatic synaptic plasticity (HSP) serves to restrain neuronal activity within a physiological range. Therefore a disruption of this mechanism may lead to destabilization in synaptic and neural circuit function. Here, we report that during HSP by neuronal activity deprivation, application of Aβ results in an aberrant over-response of the up-regulation of AMPA receptor (AMPAR)-mediated synaptic currents and cell-surface AMPAR expression. In the visual cortex, in vivo HSP induced by visual deprivation shows a similar over-response following an Aβ local injection. Aβ increases the expression of GluA2-lacking, calcium permeable AMPARs (CP-AMPARs), which are required for the initiation, but not maintenance of HSP. Both GluA2-lacking and GluA2-containing AMPARs contribute to the Aβ-mediated over-scaling of HSP. We also find that Aβ induces the dissociation of HDAC1 from the miR124 transcription factor EVI1, leading to an up-regulation of miR124 expression and increased amount of CP-AMPARs. Thus, via aberrant stimulation of miR124 expression and biogenesis of CP-AMPARs, Aβ is able to induce an over response in HSP. This Aβ-mediated dysregulation in homeostatic plasticity may play an important role in the pathogenesis of altered neural function and memory deficits in the early stages of AD.
- Published
- 2016
29. Distinct roles of neuregulin in different models of neuropathic pain
- Author
-
Pengqi Zhang, Xu Zheng, Zhifeng Deng, Dawei Dai, Aijun Zhang, Lei Yuan, Youming Lu, and Chen Xin
- Subjects
Male ,SNi ,medicine.medical_specialty ,Neurology ,Receptor, ErbB-2 ,Neuregulin-1 ,Dermatology ,Bioinformatics ,ErbB Receptors ,ErbB ,Formaldehyde ,medicine ,Animals ,ERBB4 ,business.industry ,General Medicine ,Nerve injury ,Rats ,Psychiatry and Mental health ,Hyperalgesia ,Anesthesia ,Neuropathic pain ,Neuralgia ,Neuregulin ,Neurology (clinical) ,medicine.symptom ,business - Abstract
The objective of the study was to investigate the role of neuregulin-ErbB signaling in neuropathic pain in different types of injury. Neuregulin-1(NRG-1) was injected into animals with either formalin-induced pain model or spared nerve injury (SNI) model. Formalin tests or paw withdrawal tests were performed to study the role of NRG-1 in neuropathic pain. siRNA specific to different erbB receptors were then introduced to test which specific signaling pathway was required for NRG-1 signaling in the different pain models. NRG-1 inhibits neuropathic pain after SNI in a dose-dependent manner, while NRG-1 aggravates formalin-induced neuropathic pain. ErbB2 and erbB4 receptors were activated after neuregulin administration. Knockdown of ErbB2 relieves the aggravation of NRG-1 on formalin-induced neuropathic pain, and knockdown of ErbB4 could relieve the inhibition of NRG-1 on neuropathic pain in the SNI model. NRG-1 has two distinct functions depending on the different receptor activation in different models of neuropathic pain. These novel findings may provide new therapeutic approaches for the treatment of neuropathic pain in different injury types.
- Published
- 2013
30. Influence of H2 introduction on properties in Al-doped ZnO thin films prepared by RF magnetron sputtering at room temperature
- Author
-
Shun Han, P. J. Cao, Fang Jia, Xiufang Ma, Youming Lu, Wenjun Liu, H. F. Xiang, and Deliang Zhu
- Subjects
Materials science ,Passivation ,Doping ,Analytical chemistry ,Sputter deposition ,Condensed Matter Physics ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials ,Absorption edge ,X-ray photoelectron spectroscopy ,Electrical resistivity and conductivity ,Electrical and Electronic Engineering ,Thin film ,Wurtzite crystal structure - Abstract
Al-doped ZnO (AZO) thin films were prepared by RF magnetron sputtering on quartz substrates at room temperature in different Ar + H2 ambient. The influence of H2 flow ratio on the structure and optoelectronic properties in AZO films was investigated. The prepared films are hexagonal wurtzite structure with c-axis preferred orientation, and the intensity of (002) peak decreases with the increase of H2 flow ratio. The resistivity significantly decreases with increasing the H2 flow ratio to 1.0 % by almost four orders of magnitude. X-Ray photoelectron spectroscopy and X-ray diffraction measurements exhibit that the effectiveness of Al doping in the substitutional positions is not influenced by H2 addition. We suggest that there exist a large number of acceptors in the films, the introduced H2 will passivate the acceptors, which raises both carrier concentration and Hall mobility. The increase of carrier concentration consequently induces the blue shift of optical absorption edge according to the Burstein-Moss effect.
- Published
- 2012
31. Black Phosphorus Based Field Effect Transistors with Simultaneously Achieved Near Ideal Subthreshold Swing and High Hole Mobility at Room Temperature
- Author
-
Xinke Liu, Kah-Wee Ang, Wenjie Yu, Jiazhu He, Xuewei Feng, Qiang Liu, He Jiang, null Dan Tang, Jiao Wen, Youming Lu, Wenjun Liu, Peijiang Cao, Shun Han, Jing Wu, Xi Wang, Deliang Zhu, and Zhubing He
- Subjects
Electron mobility ,Multidisciplinary ,Materials science ,business.industry ,Transistor ,Gate dielectric ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Article ,Black phosphorus ,0104 chemical sciences ,law.invention ,X-ray photoelectron spectroscopy ,law ,Gate oxide ,Subthreshold swing ,Optoelectronics ,Field-effect transistor ,0210 nano-technology ,business - Abstract
Black phosphorus (BP) has emerged as a promising two-dimensional (2D) material for next generation transistor applications due to its superior carrier transport properties. Among other issues, achieving reduced subthreshold swing and enhanced hole mobility simultaneously remains a challenge which requires careful optimization of the BP/gate oxide interface. Here, we report the realization of high performance BP transistors integrated with HfO2 high-k gate dielectric using a low temperature CMOS process. The fabricated devices were shown to demonstrate a near ideal subthreshold swing (SS) of ~69 mV/dec and a room temperature hole mobility of exceeding >400 cm2/Vs. These figure-of-merits are benchmarked to be the best-of-its-kind, which outperform previously reported BP transistors realized on traditional SiO2 gate dielectric. X-ray photoelectron spectroscopy (XPS) analysis further reveals the evidence of a more chemically stable BP when formed on HfO2 high-k as opposed to SiO2, which gives rise to a better interface quality that accounts for the SS and hole mobility improvement. These results unveil the potential of black phosphorus as an emerging channel material for future nanoelectronic device applications.
- Published
- 2016
32. Light-Harvesting in n-ZnO/p-Silicon Heterojunctions
- Author
-
B. Yao, D.Z. Shen, L. L. Li, Youming Lu, Bucheng Li, Changsheng Shan, and B. Chu
- Subjects
Sunlight ,Materials science ,Silicon ,business.industry ,Photovoltaic system ,Energy conversion efficiency ,chemistry.chemical_element ,Heterojunction ,Zinc ,Condensed Matter Physics ,Photochemistry ,medicine.disease_cause ,Electronic, Optical and Magnetic Materials ,chemistry ,Materials Chemistry ,Ultraviolet light ,medicine ,Optoelectronics ,Electrical and Electronic Engineering ,business ,Ultraviolet - Abstract
Zinc oxide (ZnO) films were deposited onto Si to form n-ZnO/p-Si heterojunctions. Under the illumination of by both ultraviolet (UV) light and sunlight, obvious photovoltaic behavior was observed. It was found that the conversion efficiency of the heterojunctions increased significantly with increasing thickness of the ZnO film, and the mechanism for light-harvesting in the heterojunctions is discussed. The results suggest that ZnO films may be helpful to increasing the harvesting of UV photons, thus decreasing the thermalization loss of UV energy in Si-based solar cells.
- Published
- 2010
33. An approach to enhanced acceptor concentration in ZnO:N films
- Author
-
J. Y. Zhang, Youming Lu, B. Yao, D.Z. Shen, Bucheng Li, X.W. Fan, L. L. Li, and Changsheng Shan
- Subjects
Photoluminescence ,Materials science ,Mechanical Engineering ,Inorganic chemistry ,Doping ,chemistry.chemical_element ,Nitrogen ,Acceptor ,chemistry ,Chemical engineering ,Mechanics of Materials ,Nitrogen plasma ,Solid mechanics ,General Materials Science ,Spectroscopy ,Electrical conductor - Abstract
Owing to the low doping concentration of nitrogen and strong compensation of intrinsic donors, the attainment of highly conductive p-type ZnO films remains one of the largest challenges for the application of ZnO. An approach has been proposed to increase the doping concentration of nitrogen in ZnO by exposing the ZnO:N films in the ambient of nitrogen plasma periodically in this paper. Hall measurements and photoluminescence spectroscopy indicate that this approach is effective in improving the hole concentration in ZnO films. Under the optimized conditions, a p-type ZnO film with a hole concentration of 1.68 × 1018 cm−3 has been achieved.
- Published
- 2010
34. Synaptic mechanism in Alzheimer’s disease: a selective degeneration of an excitatory synaptic pathway in the CA1 hippocampus that controls spatial learning and memory in Alzheimer’s disease
- Author
-
L-Q Zhu, Xin Yang, Huanhuan Yan, Lei Pei, Qing Tian, Chengye Yao, Tian Tian, Youming Lu, Xiong Li, Hao Li, Deming Liu, and Jun Wu
- Subjects
Mechanism (biology) ,Ca1 pyramidal neuron ,02 engineering and technology ,Degeneration (medical) ,Disease ,Biology ,021001 nanoscience & nanotechnology ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,0302 clinical medicine ,nervous system ,Spatial learning ,Excitatory postsynaptic potential ,0210 nano-technology ,Molecular Biology ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Synaptic mechanism in Alzheimer’s disease: a selective degeneration of an excitatory synaptic pathway in the CA1 hippocampus that controls spatial learning and memory in Alzheimer’s disease
- Published
- 2018
35. AlGaN/GaN Metal-Oxide-Semiconductor High-Electron-Mobility Transistor with Polarized P(VDF-TrFE) Ferroelectric Polymer Gating
- Author
-
Shaojun Chen, Youming Lu, Peijiang Cao, Jing Wu, Jiazhu He, Deliang Zhu, Xinke Liu, Sun Han, Wenjie Yu, Leng Seow Tan, Pannirselvam Somasuntharam, Zhihong Liu, Wenjun Liu, and Dan Tang
- Subjects
Diffraction ,Multidisciplinary ,Materials science ,Equivalent series resistance ,business.industry ,Transistor ,Heterojunction ,High-electron-mobility transistor ,Ferroelectricity ,Article ,law.invention ,law ,Electric field ,Optoelectronics ,Fermi gas ,business - Abstract
Effect of a polarized P(VDF-TrFE) ferroelectric polymer gating on AlGaN/GaN metal-oxide-semiconductor high-electron-mobility transistors (MOS-HEMTs) was investigated. The P(VDF-TrFE) gating in the source/drain access regions of AlGaN/GaN MOS-HEMTs was positively polarized (i.e., partially positively charged hydrogen were aligned to the AlGaN surface) by an applied electric field, resulting in a shift-down of the conduction band at the AlGaN/GaN interface. This increases the 2-dimensional electron gas (2-DEG) density in the source/drain access region of the AlGaN/GaN heterostructure and thereby reduces the source/drain series resistance. Detailed material characterization of the P(VDF-TrFE) ferroelectric film was also carried out using the atomic force microscopy (AFM), X-ray Diffraction (XRD) and ferroelectric hysteresis loop measurement.
- Published
- 2015
36. 厚层灰岩油藏岩溶纵向分带研究
- Author
-
Quangong Qu, Jingxuan Zhang, Youming Lu, and Fengyun Zhu
- Subjects
Geophysics ,Geology - Abstract
In district 4 of the Tahe Oilfield, the Ordovician Yingshan Formation was most petroliferous. Marine carbonate rocks with big thickness were widespread. Secondary pores, including dissolution pores, fractures and caves, served as the main reservoir spaces, while primary pores were poorly developed. According to modern karst hydraulic unit theory, a conceptual model of karst was established. Three palaeo-hydraulic zones were identified:vadose zone (including infiltration sub-zone and percolation sub-zone), phreatic zone and tranquil zone. The distribution of reservoirs was described using stochastic seismic inversion technology. The reservoirs were controlled by palaeo-hydraulic zones vertically and karst landforms horizontally, which was proved by field work.
- Published
- 2015
37. Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors
- Author
-
Yang Ping Fu, Shu Hong Liu, Jian Wang, Youming Lu, and Jerry H. Wang
- Subjects
Recombinant Fusion Proteins ,Genetic Vectors ,Hippocampus ,Hippocampal formation ,Receptors, N-Methyl-D-Aspartate ,Brain Ischemia ,Rats, Sprague-Dawley ,Organ Culture Techniques ,Serine ,Animals ,Amino Acid Sequence ,Phosphorylation ,Receptor ,Cell Death ,Chemistry ,Kinase ,Pyramidal Cells ,General Neuroscience ,Cyclin-dependent kinase 5 ,Excitatory Postsynaptic Potentials ,food and beverages ,Cyclin-Dependent Kinase 5 ,Cyclin-Dependent Kinases ,Peptide Fragments ,Rats ,nervous system ,Reperfusion Injury ,Mutation ,Nerve Degeneration ,NMDA receptor ,Excitatory Amino Acid Antagonists ,Neuroscience ,Intracellular - Abstract
CA1 pyramidal neurons degenerate after transient forebrain ischemia, whereas neurons in other regions of the hippocampus remain intact. Here we show that in rat hippocampal CA1 neurons, forebrain ischemia induces the phosphorylation of the N-methyl-D-aspartate (NMDA) receptor 2A subunit at Ser1232 (phospho-Ser1232). Ser1232 phosphorylation is catalyzed by cyclin-dependent kinase 5 (Cdk5). Inhibiting endogenous Cdk5, or perturbing interactions between Cdk5 and NR2A subunits, abolished NR2A phosphorylation at Ser1232 and protected CA1 pyramidal neurons from ischemic insult. Thus, we conclude that modulation of NMDA receptors by Cdk5 is the primary intracellular event underlying the ischemic injury of CA1 pyramidal neurons.
- Published
- 2003
38. [Untitled]
- Author
-
Yichun Liu, Xiwu Fan, Dongxu Zhao, Dezhen Shen, Youming Lu, and Jiying Zhang
- Subjects
Materials science ,Annealing (metallurgy) ,Band gap ,Analytical chemistry ,Mineralogy ,Nanoparticle ,Cathodoluminescence ,General Chemistry ,Condensed Matter Physics ,Electronic, Optical and Magnetic Materials ,Biomaterials ,chemistry.chemical_compound ,chemistry ,Ternary compound ,Materials Chemistry ,Ceramics and Composites ,Transmittance ,Thin film ,Sol-gel - Abstract
The MgxZn1−xO alloy thin films were synthesized on Si and quartz substrates by the sol-gel deposition method. The transmittance and cathodoluminescence spectra of the Mg0.05Zn0.95O and Mg0.15Zn0.85O nanoparticle films were obtained at room temperature. It was found that the bandgap of Mg0.05Zn0.95O and Mg0.15Zn0.85O films is as large as 3.72 eV and 3.79 eV, respectively. The ultraviolet emission peaks are located at 376 nm and 370 nm, respectively, for the samples annealed at 600°C. When the annealing temperature is elevated to 1000°C, the band-gap decreases to 3.42 eV and an emission line related to the deep-level defect appears at 500 nm. The mechanism behind these phenomena is discussed.
- Published
- 2002
39. Lysosomal enzyme cathepsin D protects against alpha-synuclein aggregation and toxicity
- Author
-
Kevin A. Roth, Lisa D Speake, Talene A. Yacoubian, Yasuo Uchiyama, Takeshi Iwatsubo, Scott M. Wilson, Stephen L. Crimmins, David G. Standaert, Jianhua Zhang, Ken C. Walls, John J. Shacka, Qiuli Liang, Zuo-Lei Xie, Liyan Qiao, Lisheng Peng, YouMing Lu, Rachael Parks, Donna M. Crabtree, Shusei Hamamichi, Kim A. Caldwell, Yi Zhou, Guy A. Caldwell, and Lonnie Schneider
- Subjects
Proteasome Endopeptidase Complex ,Programmed cell death ,animal diseases ,Cathepsin D ,Biology ,Neuroprotection ,lcsh:RC346-429 ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,Phagosomes ,medicine ,Animals ,Humans ,Point Mutation ,heterocyclic compounds ,RNA, Messenger ,Caenorhabditis elegans ,Protein Structure, Quaternary ,Molecular Biology ,lcsh:Neurology. Diseases of the nervous system ,030304 developmental biology ,Neurons ,Alpha-synuclein ,0303 health sciences ,Lewy body ,Caspase 3 ,Research ,Neurodegeneration ,Autophagy ,medicine.disease ,Molecular biology ,Up-Regulation ,nervous system diseases ,Mice, Inbred C57BL ,Neuroprotective Agents ,nervous system ,chemistry ,alpha-Synuclein ,Neuronal ceroid lipofuscinosis ,Lysosomes ,030217 neurology & neurosurgery - Abstract
α-synuclein (α-syn) is a main component of Lewy bodies (LB) that occur in many neurodegenerative diseases, including Parkinson's disease (PD), dementia with LB (DLB) and multi-system atrophy. α-syn mutations or amplifications are responsible for a subset of autosomal dominant familial PD cases, and overexpression causes neurodegeneration and motor disturbances in animals. To investigate mechanisms for α-syn accumulation and toxicity, we studied a mouse model of lysosomal enzyme cathepsin D (CD) deficiency, and found extensive accumulation of endogenous α-syn in neurons without overabundance of α-syn mRNA. In addition to impaired macroautophagy, CD deficiency reduced proteasome activity, suggesting an essential role for lysosomal CD function in regulating multiple proteolytic pathways that are important for α-syn metabolism. Conversely, CD overexpression reduces α-syn aggregation and is neuroprotective against α-syn overexpression-induced cell death in vitro. In a C. elegans model, CD deficiency exacerbates α-syn accumulation while its overexpression is protective against α-syn-induced dopaminergic neurodegeneration. Mutated CD with diminished enzymatic activity or overexpression of cathepsins B (CB) or L (CL) is not protective in the worm model, indicating a unique requirement for enzymatically active CD. Our data identify a conserved CD function in α-syn degradation and identify CD as a novel target for LB disease therapeutics.
- Published
- 2008
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