Basic InformationName：Qianru Zhao
Gender： Female
Date of Birth： 14/7/1990 Major: Neurobiology
Phone Number: +86 18086416853
Email: qianru.zhao@yahoo.com
Ph.D. Supervisor: Prof. Yan’ai Mei
Email: yamei@fudan.edu.cn
Working Experience：
Postdoctoral Scientist in Department of Pharmacology, University of Oxford
Co-supervisor：
Porf. Peter Somogyi
Email: peter.somogyi@pharm.ox.ac.uk
Current Position Lecturer in Department of Pharmacology, South-Central University for Nationalities
Working Group Professor Shijin Yin
Email: 845450830@qq.com
Address: Department of Pharmacology, South-Central University for Nationalities，182 Minzu Road，Hongshan District, Wuhan
Education 9/2013-7/2018：Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai
DPhil, Major in Neurobiology
9/2009-7/2013：School of Life Sciences, Fudan University, Shanghai
B.S., Major in Bioscience
Meetings
Attended 11/20142014 Annual Summary Meeting of Key Project of Chinese National Programs for Fundamental Research and Development (973 Program) Xi’an, China
9/2015 The 6th Federation of Asian-Oceanian Neuroscience Societies Congress and the 11th Biennial Conference of China Neuroscience Society
Wuzhen, China
7/2016 39th Annual Meeting of the Japan Neuroscience Society Yokohama, Japan
8/2017 15th European Neurology CongressLondon, UK
Publications
1. Zhao QR, Lu JM, Yao JJ, Zhang ZY, Ling C, Mei YA*. Neuritin reverses deficits in murine novel object associative recognition memory caused by exposure to extremely low-frequency (50 Hz) electromagnetic fields. Scientific Reports. 2015 Jul 3; 5: 11768. doi: 10.1038/srep11768.
2. Yao JJ1#, Zhao QR1#, Liu DD, Chow CW*, Mei YA*. Neuritin Up-regulates Kv4.2 α-Subunit of Potassium Channel Expression and Affects Neuronal Excitability by Regulating the Calcium-Calcineurin-NFATc4 Signaling Pathway. Journal of Biological Chemistry. 2016, 291(33): 17369–17381. (# Co-first author)
3. Zhao QR*, Lu JM, Li ZY, Mei YA*. Neuritin promotes neurite and spine growth in rat cerebellar granule cells via L-type calcium channel-mediated calcium influx. Journal of Neurochemistry. 19 June 2018, published online. (*Corresponding author)
4. He YL, Wang K, Zhao QR, Mei YA*. Cyproheptadine regulates pyramidal neuron excitability in mouse medial prefrontal cortex. Neuroscience Bulletin. 18 April 2018, published online.
5. Yao JJ, Zhao QR, Lu JM, Mei YA*. Functions and the related signaling pathways of the neurotrophic factor neuritin. Acta Pharmacologica Sinica. 29 Mar 2018, published online.
6. Liu DD, Lu JM, Zhao QR, Hu C, Mei YA*. Growth differentiation factor-15 promotes glutamate release in medial prefrontal cortex of mice through upregulation of T-type calcium channels. Scientific Reports. 2016 Jun 29; 6: 28653. doi: 10.1038/srep28653.
7. Liu DD, Ren Z, Yang G, Zhao QR, Mei YA*. Melatonin protects rat cerebellar granule cells against electromagnetic field-induced increases in Na+ currents through intracellular Ca2+ release. Journal of Cellular and Molecular Medicine. 2014, 305(2): 197-206.
8. Yao JJ1#, Sun J1#, Zhao QR, Wang CY, Mei YA*. Neuregulin-1/ErbB4 signaling regulates Kv4.2-mediated transient outward K+ current through the Akt/mTOR pathway. American Journal of Physiology - Cell Physiology. 2013, 18(6): 1060-1070.
9. Wang K, Lu JM, Xing ZH, Zhao QR, Hu LQ, Xue L, Zhang J, Mei YA*. Effect of 1.8 GHz radiofrequency electromagnetic radiation on novel object associative recognition memory in mice. Scientific Reports, 2017 Mar 17 (7): 44521.
Skills
1. Animal behavior test
3. Western blot
5. Immunofluorescence
7. Neuron culture
9. Histochemical staining
11. Neuron reconstruction
13. AAV and Lentivirus construction
15. Patch clamp on single cell and brain slice
17. In situ sequencing2. Stereotaxic injection
4. RT-PCR; Q-PCR
6. Molecular cloning
8. Calcium imaging
10. Microscope imaging
12. Genotyping of transgenic animal genes
14. Spike2 and pCLAMP
16. MATLAB
Research
Undergraduate:
Neuregulin-1/ErbB4 signaling regulates Kv4.2-mediated transient outward K+ current through the Akt/mTOR pathway.
Neuregulin-1(NRG-1) is a member of neurotrophic factor, which is required for differentiation, migration and development of neurons. However, few studies have investigated the role of NRG-1 on voltage-gated ion channels. Our data reveal, for the first time, that stimulation of ErbB4 signaling by NRG-1 upregulates the expression of K+ channel proteins via activation of the Akt/mTOR signaling pathway and plays an important role in neuronal development and maturation. (Yao JJ et.al., 2013) In this project, I mainly worked on whether the Akt/mTOR pathway is required for the NRG-1-induced upregulation of the IA density and KV4.2 (α-subunit of the IA channel) expression in rat cerebellar granule neurons (CGNs). We blocked Akt activity by LY294002 or mTOR activity by rapamycin and found that they could both prevent the NRG-1-mediated increase in KV4.2 protein expression and IA density, which proved the Akt/mTOR pathway is required for NRG-1 to upregulate the IA density and KV4.2 expression.
Postgraduate (Ph.D)
The Effect and Mechanism of Neuritin on Neurite and Spine Growth.
Part 1: Neuritin reverses deficits in murine novel object associative recognition memory caused by exposure to extremely low-frequency electromagnetic fields.
t is a sub-project of Key Project of Chinese National Programs for Fundamental Research and Development, which aims at revealing the effects of electromagnetic fields on health. In this study, we used a mouse model to examine the effects of exposure to extremely low-frequency (50 Hz) electromagnetic fields (ELFMFs) on a recognition memory task and morphological changes of hippocampal neurons. My contribution is conducting and analyzing the animal behavior and neuronal morphology experiments. The data showed that ELFMFs exposure (1 mT, 12 h/day) induced a time-dependent deficit in novel object associative recognition memory and also decreased dendritic spine density of hippocampal pyramidal cells.
Neuritin, also known as candidate plasticity gene (CPG)15, was identified as an important neurotrophin that is expressed in the developing nervous system. It plays multiple roles in the process of neural development, such as promoting neurite outgrowth and arborization. So I used an adeno-associated virus (AAV) vector to overexpress neuritin in hippocampus CA1 region and found the increase of spine density in pyramidal neurons. This increase was paralleled with recovery from ELFMFs exposure-induced deficits in recognition memory.
Our study provides evidence for the association between ELFMFs exposure, impairment of recognition memory, and resulting changes in hippocampal dendritic spine density. Neuritin prevented this ELFMFs-exposure-induced effect by increasing the hippocampal spine density. (Zhao QR et.al., 2015)
Part 2: Neuritin Up-regulates Kv4.2 α-Subunit of Potassium Channel Expression and Affects Neuronal Excitability by Regulating the Calcium-Calcineurin-NFATc4 Signaling Pathway.
Neuritin is an important neurotrophin that regulates neural development, synaptic plasticity, and neuronal survival. The previous work in our lab showed that neuritin up-regulates transient potassium outward current (IA) subunit KV4.2 expression and increases IA densities, in part by activating the insulin receptor (IR) signaling pathway. Molecular mechanisms of neuritin induced KV4.2 expression remain elusive. In this study, we report that the Ca2+/calcineurin (CaN)/nuclear factor of activated T-cells (NFAT) c4 axis is required for neuritin-induced KV4.2 transcriptional expression and potentiation of IA densities in CGNs.
My contribution is designing, performing, and analyzing all the experiments with Jinjing Yao. We found that neuritin elevates intracellular Ca2+ and increases KV4.2 expression and IA densities; this effect was sensitive to CaN inhibition and was eliminated in Nfatc4-/- mice but not in Nfatc2-/- mice. Stimulation with neuritin significantly increased nuclear accumulation of NFATc4 in CGNs and HeLa cells, which expressed IR. Furthermore, NFATc4 was recruited to the KV4.2 gene promoter loci detected by luciferase reporter and chromatin immunoprecipitation assays. More importantly, data obtained from cortical neurons following AAV-mediated overexpression of neuritin indicated that reduced neuronal excitability and increased formation of dendritic spines were abrogated in the Nfatc4-/- mice. Together, these data demonstrate an indispensable role for the CaN/NFATc4 signaling pathway in neuritin-regulated neuronal functions. (Yao JJ et.al., 2016）
Part 3: Neuritin promotes neurite and spine growth in rat cerebellar granule cells via L-type calcium channel-mediated calcium influx.
Neuritin is a neurotrophic factor that is activated by neural activity and neurotrophins. Its major function is to promote neurite growth and branching; however, the underlying mechanisms are not fully understood. To address this issue, this part of our work investigated the effects of neuritin on neurite and spine growth and intracellular Ca2+ concentration in rat cerebellar granule neurons (CGNs). Incubation of CGNs for 24 h with neuritin increased neurite length and spine density; this effect was mimicked by insulin and abolished by inhibiting IR or mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) activity. Calcium imaging and western blot analysis revealed that neuritin enhanced the increase in intracellular Ca2+ level induced by high K+ and stimulated the cell surface expression of CaV1.2 and CaV1.3 α subunits of the L-type calcium channel, which was suppressed by inhibition of IR or MEK/ERK. Treatment with inhibitors of L-type calcium channels, calmodulin and CaN abrogated the effects of neuritin on neurite length and spine density. A similar result was obtained by silencing NFATc4, which is known to be activated by neuritin in CGNs. These results indicate that IR and ERK signaling as well as the Ca2+/CaN/NFATc4 axis mediate the effects of neuritin on neurite and spine growth in CGNs. (Zhao QR et.al., 2018）
Postdoctoral research:
Medial septum neurons with low-rhythmic firing preferentially innervate CA3 and the dentate gyrus
The medial septum/diagonal band (MS/DB) nuclei is part of the limbic system and in the midline and the basal forebrain. The MS/DB is not only a relay station, but also processes information related to locomotion, attention and reinforcement learning, as well as affecting the running velocity, navigation and context-dependent memory processes. MS/DB plays important role in governing theta waves in hippocampus and other cortical areas via cholinergic, GABAergic and glutamatergic projections. Using in vivo recordings in awake mice, the group of Prof. Peter Somogyi recently discovered two subsets of high-rhythmic GABAergic neurons in MS/DB, named Teevra and Orchid cells. They fire on different phases of theta oscillation and innervate separate cortical areas. (Joshi et.al., Neuron 2017; Viney et.al., eLife 2018) Besides these two subpopulations, a group of low-rhythmic neurons in medial septum have also been found. The firing of these neurons was suppressed during sharp-wave ripples and most of them innervated interneurons in the CA3 and dentate gyrus. I was mainly devoted to the project of the low-rhythmic neurons in MS/DB. I used software such as Spike2 and MATLAB to test for theta-phase coupling and to analyze the rhythmicity of the neurons, and applied HRP-based diaminobenzidine reactions and immunofluorescence to trace the innervation areas and find targets. At the same time, I learned the methods for in vivo juxtacellular recording, in situ sequencing and in situ hybridization that can be applied to future projects.
Current research：
Effects and mechanism of bioactive peptides in scorpion venom on ion channels
Scorpion is one of the oldest species on earth. It has a great diversity and distributes widely in major terrestrial ecosystems. When hunting, a pair of venom glands in the tail of a scorpion release neurotoxic venom to paralyze or kill its prey. The venom is extremely important for survival of the scorpions. Scorpion venom has complex components, including protein and non-protein compounds. The non-protein components mainly contain mucopolysaccharides, lipids, inorganic salts, nucleotides, free amino acids and biological amines. In contrast, the protein part is more abundant, not only including certain amount of phosphatase, hyaluronidase, metalloproteinase and other enzymes, but also bioactive peptides which selectively act on many kinds of ion channels. With the increasing abundance of high-throughput screening technologies, the researches on the composition, structure and function of scorpion venom are also deepening, and many of scorpion venoms have become the leading substances for the development of new drugs or important molecular tools for pathophysiological research. The Professor Shijin Yin’s group which I joined is devoted to the research on those bioactive peptides in scorpion venom to explore their effects on different types of ion channels and try to develop them as drugs to cure diseases in human.
