1.TLR5 and transplantation tolerance
Research Leader
Name: Hou Guihua
Title: Professor
Tel: 13964050965
Email: ghhou@sdu.edu.cn;ghhou1@hotmail.com
Name of Scientist(s)
Sun hukui; Hao jing
Five Keywords (including technology used)
TLR5,allorejection;tolerance; Flagellin; autoradioimaging
Project period (year-month-date – year-month-date)
2014.1-2017.12
Project description
To investigate whether recombinant Flagellin could prolong survival of allograft and underlying mechanisms with mice allotransplantation model.
Research Progress
It was just the first year, and had proved that rFlic could prolong the survival of allograft associated with TLR5 pathway.
Source of funding
National Natural Science Foundation of China
2.The mechanism underlying the inhibitory effect of oxytocin the of mast cells degranulation in the gut
Research Leader
Name: Chuanyong Liu
Title: Professor
Tel: +86-531-88382098; +86-13031706480
Email: liucy@sdu.edu.cn
Name of Scientist(s)
Jingxin Li, Bing Xue, Xuelian Ma, Rong Wang, Shuanglian Wang
Five Keywords (including technology used)
Oxytocin, enteric nervous system, mast cell, sensation
Project period (year-month-date – year-month-date)
2015.01-2018.12
Project description
Our hypothesis is that endogenous oxytocin in the gut inhibitory the degranulation of the mast cell in the gut, so exert an antinociception effect in IBS patients.
Research Progress
We have got some preliminary data that support our hypothesis.
Source of funding
Natural Scientific Foundation of China (NSFC)
3.Role of BDNF in memory formation and extinction on the basis of neural circuitry
Research Leader
Name: Zhe-Yu Chen
Title: Professor
Tel: 86-531-88382336
Email: zheyuchen@sdu.edu.cn
Name of Scientist(s)
Zhe-Yu Chen, Yue Wang, Bo Su, Hui Yu
Five Keywords (including technology used)
BDNF; TrkB receptor; CTA memory; memory formation; memory extinction
Project period (year-month-date – year-month-date)
2012.01-2016.12
Project description
Brain derived neurotrophic factor (BDNF) is widely distributed in the central nervous system and plays an important role in synaptic plasticity, which synthesis and secretion are regulated by neuronal activity. The role of BDNF in learning and memory has been extensively studied, however most of these studies are focused on one single brain region such as hippocampus and amygdale and there lacks the study on the basis of BDNF neural circuitry. We previous showed that BDNF was involved in the acquisition and extinction of conditioned taste aversion (CTA) memory, a cortical learning, via distinct neural circuitry. In this study, we will investigate the role of BDNF synthesis and secretion in CTA memory formation and extinction on the basis of BDNF neural circuitry with combined behavior, molecular and transgenic mouse approaches. Furthermore, we will try to reveal the molecular mechanism underlying the role of BDNF in neuronal structure regulation and its relevant to learning and memory. The goal of this study is to further understand the role of BDNF in learning and memory on the neural circuitry basis and provide new approach to treat memory disorders.
Research Progress
Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB), play a critical role in memory extinction. However, the detailed role of BDNF in memory extinction on the basis of neural circuit has not been fully understood. Here, we aim to investigate the role of BDNF signaling circuit in mediating conditioned taste aversion (CTA) memory extinction of the rats. We found region-specific changes in BDNF gene expression during CTA extinction. CTA extinction led to increased BDNF gene expression in the basolateral amygdala (BLA) and infralimbic prefrontal cortex (IL) but not in the central amygdaloid nucleus (CeA) and hippocampus (HIP). Moreover, blocking BDNF signaling or exogenous microinjection of BDNF into the BLA or IL could disrupt or enhance CTA extinction, which suggested that BDNF signaling in the BLA and IL are necessary and sufficient for CTA extinction. Interestingly, we found that microinjection of BDNF neutralizing antibody into the BLA could abolish the extinction training induced BDNF mRNA levels increase in the IL, but not vice versa, demonstrating BDNF signaling is transmitted from the BLA to IL during extinction. Finally, the accelerated extinction learning by infusion of exogenous BDNF in the BLA could also be blocked by IL infusion of BDNF neutralizing antibody rather than vice versa, indicating the IL but not BLA is the primary action site of BDNF in CTA extinction. Together, these data suggest that BLA-IL circuit regulates CTA memory extinction by identifying BDNF as a key regulator.
Source of funding
NSFC
4.Therapeutic effects of insulin-like growth factor-1 on paclitaxel-induced peripheral neuropathy
Research Leader
Name: Zhenzhong Li
Title: Professor
Tel: 86-158-6379-3602
Email: zli@sdu.edu.cn
Name of Scientist(s)
Zhen Liu, Hao Li, Huaxiang Liu
Five Keywords (including technology used)
paclitaxel; insulin-like growth factor-1; dorsal root ganglion; neuropeptide; neuropathy
Project period (year-month-date – year-month-date)
2013-01-01–2015-12-31
Project description
Paclitaxel (PT), one of the most commonly used anti-neoplastic agent in theTaxusspecies, is isolated from the bark of the North AmericanTaxus brevifoliaand produces a dose-limiting side effect that is chronic sensory peripheral neuropathy and subsequent neuropathic pain that is resistant to standard analgesics. PT-induced neurotoxicity is a significant problem associated with successful treatment of cancers. The detailed mechanisms in peripheral neurotoxicity caused by PT are not yet completely elucidated. One of the mechanisms is that PT affects the peripheral sensory endings to alter neurotransmitter, i.e. calcitonin gene-related peptide (CGRP), release and may contribute to the symptoms in PT-induced neuropathy. PT also caused neuropathic muscle pain. PT-induced neuropathy developed persistent muscle hyperalgesia, which evolved in parallel in muscle in rat animal models. Nowadays, there are no validated drugs to control the neuropathic pain induced by PT. Insulin-like growth factor-1 (IGF-1) is a growth-promoting peptide hormone that has been shown to have neurotrophic properties. The aim of the present study is to explore the capacity of the therapeutic effects of IGF-1 on PT-induced peripheral neuropathy. This reseach may provide novel evidence that IGF-1 and its receptor signaling system might be the potential new targets for the treatment of PT-related chemotherapy-induced peripheral neuropathy, a medical condition for which few effective therapeutic options are available.
Research Progress
“Insulin-like growth factor-1 attenuates apoptosis and protects neurochemical phenotypes of dorsal root ganglion neurons with paclitaxel-induced neurotoxicity in vitro” is published online.
Source of funding
The Science and Technology Development Project ofJinanMunicipalityofShandongProvinceofChina (No. 201302040)
5.Mechanism Research on GSN in Multiple Sclerosis and EAE
Research Leader
Name: Shilian Liu
Title: Professor
Tel: 0531-88382346-0
Email: liushilian@sdu.edu.cn
Name of Scientist(s)
Lianying Zhang; Yi Lu
Five Keywords (including technology used)
Gelsolin; Multiple Sclerosis; EAE; EASS; Proteomics
Project period (year-month-date – year-month-date)
2013.1-2016.12
Project description
The potential functions of GSN and DBP are attracting more and more attention in recent years. In our previous research, close association between GSN, vitamin binding protein(DBP) and multiple sclerosis(MS) was discoverd. GSN significantly reduced in cerebrospinal fluid(CSF) and serum of MS patients compared with control group. In addition, GSN was discoverd interacting with some novel proteins and small molecule compounds in other inflammatory diseases, which would involved in preventing tissue from inflammatory injury and immune regulation. These findings suggested GSN would play potiential roles in various biology progresses and biomolecule interaction networks in MS/EAE. In our project, animal models of experimental autoimmune encephalomyelitis (EAE), primary cultured neurons model of rats and human CSF/serum would be analysed by molecular biology, proteomics, immunology and animal model technology in order to investigate the function and the mechanism of GSN(including its level and activity) in the process of MS from a systems biology point of view, seek nevol biomolecules related to MS/EAE, which would interact with GSN, and expand GSN biological network access. Our project would be of great clinical significance to study the pathogenesis of MS and search for potential biomarkers and drug targets.
Research Progress
Published papers:
1, Zhu Y, Qin Z, Gao J, Yang M, Qin Y, Shen T,Liu S*.Vitamin D Therapy in Experimental Allergic Encephalomyelitis Could be Limited by Opposing Effects of Sphingosine 1-Phosphate and Gelsolin Dysregulation.Mol Neurobiol.2014 Apr 11. (Liu S *，Corresponding Author；IF=5.843)
2.Yang M, Qin Z, Zhu Y, Li Y, Qin Y, Jing Y,Liu S*. Vitamin D-bindingProtein in Cerebrospinal Fluid is Associated with Multiple Sclerosis Progression.Mol Neurobiol.2013 Jun;47(3):946-956 (Liu S *，Corresponding Author；IF=5.843)
Source of funding
The National Natural ScienceFund Committee70Millionyuan
