Key Laboratory of Medical Neurobiology

Hangzhou, China

Key Laboratory of Medical Neurobiology

Hangzhou, China
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News Article | May 11, 2017
Site: www.eurekalert.org

New research in The FASEB Journal suggests that the protein Efr3a regulates the BDNF-TrkB signaling pathway, which plays an important role in regulating learning and memory New research published online in The FASEB Journal sheds important light on the inner workings of learning and memory. Specifically, scientists show that a plasma membrane protein, called Efr3, regulates brain-derived neurotrophic factor-tropomyosin-related kinase B signaling pathway (BNDF-TrkB) and affects the generation of new neurons in the hippocampus of adult brains. In turn, this generation of new neurons plays a significant role in learning and memory. "Our study demonstrates that Efr3a is associated with BDNF signaling and adult neurogenesis, which are important for learning and memory," said Binggui Sun, Ph.D., a researcher involved in the work at the Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. "We hope our results will provide new insights into the mechanisms underlying learning and memory." To draw their conclusions, Sun and colleagues bred Efr3af/f mice and then crossed these mice with another group to delete Efr3a, one of the Efr3 isoforms, specifically in the brain. Brain-specific ablation of Efr3a promoted adult hippocampal neurogenesis by increasing survival and maturation of newborn neurons without affecting their dendritic tree morphology. Also, the BDNF-TrkB signaling pathway was enhanced in the hippocampus of Efr3a-deficient mice, as reflected by increased expression of BDNF-TrkB, and the downstream molecules, including phospho-MAPK (mitogen-activated protein kinase) and phospho-Akt. "This study once again emphasizes the extreme importance of neurogenesis specifically linked to neurotrophic signaling in the hippocampus." said Thoru Pederson, Ph.D., Editor-in-Chief of The FASEB Journal. "We are again reminded of how far we have come from the era in which neurogenesis in the adult mammalian brain was not believed to even occur." Submit to The FASEB Journal by visiting http://fasebj. , and receive monthly highlights by signing up at http://www. . The FASEB Journal is published by the Federation of the American Societies for Experimental Biology (FASEB). It is among the world's most cited biology journals according to the Institute for Scientific Information and has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century. FASEB is composed of 30 societies with more than 125,000 members, making it the largest coalition of biomedical research associations in the United States. Our mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy. Details: Qi Qian, Qiuji Liu, Dongming Zhou, Hongyu Pan, Zhiwei Liu, Fangping He, Suying Ji, Dongpi Wang, Wangxiao Bao, Xinyi Liu, Zhaoling Liu, Heng Zhang, Xiaoqin Zhang, Ling Zhang, Mingkai Wang, Ying Xu, Fude Huang, Benyan Luo, and Binggui Sun. Brain-specific ablation of Efr3a promotes adult hippocampal neurogenesis via the brain-derived neurotrophic factor pathway. FASEB J. doi:10.1096/fj.201601207R ; http://www.


Zhang L.-S.,Zhejiang University | Zhang L.-S.,Key Laboratory of Medical Neurobiology | Hu X.-Y.,Zhejiang University | Yao L.-Y.,Zhejiang University | And 5 more authors.
European Neurology | Year: 2013

Post-stroke depression (PSD) is a common yet severe sequela of stroke, and is often accompanied with somatic symptoms. Duloxetine, a new serotonin-norepinephrine reuptake inhibitor, may help to prevent depression after stroke. 95 ischemic stroke patients without depression were randomly divided into two groups: duloxetine group (n = 47) and control group (n = 48). Patients in the control group received routine ischemic stroke therapy, whereas patients in the duloxetine group received duloxetine (dose range 30-90 mg) for 12 weeks in addition to routine therapy. Follow-up observations lasted for 24 weeks. The Hamilton Depression Scale was used to measure depression, and the National Institute of Stroke Scale, Mini-Mental State Examination, Activities of Daily Living Scale (Chinese version) and Short Form 36 Health Survey Questionnaire were used to assess neurological function, cognitive function, rehabilitation from stroke and quality of life. Results showed that in general, duloxetine spared ischemic stroke patients from both minor and major depression by 16%. In addition, duloxetine helped patients to rehabilitate more rapidly from stroke, and was associated with better cognitive function and quality of life. In conclusion, the prophylactic use of duloxetine not only decreased the incidence of PSD, but also promoted rehabilitation, cognitive function and quality of life. © 2013 S. Karger AG, Basel.


Fan J.-M.,Zhejiang University | Fan J.-M.,Wenzhou University | Chen X.-Q.,Zhejiang University | Chen X.-Q.,Key Laboratory of Medical Neurobiology | And 4 more authors.
Neuroendocrinology Letters | Year: 2014

Prenatal stress (PNS) is associated with increased biological risk for mental disorders such as anxiety and depression later in life, and stress appear to be additive to the PNS influences. Among the most widely cited and accepted alternative hypotheses of anxiety and depression is dysfunction of the HPA axis, a system that is central in orchestrating the stress response. Therefore, understanding how PNS exerts profound effects on the HPA axis and stress-sensitive brain functions including anxiety and depression has significant clinical importance. In this mini-review, we will focus on novel and evolving concepts regarding the potential mechanisms underlying the short and long-term effects of PNS involving CRH peptide family. We present evidence demonstrating prenatal hypoxia exposure induced anxiety-like behavior in adult male rat offspring and CRHR1 in PVN of the hypothalamus is involved.


Yang W.,Zhejiang University | Yang W.,Key Laboratory of Medical Neurobiology | Yang W.,University of Leeds | Jiang L.-H.,University of Leeds
Methods in Molecular Biology | Year: 2013

Ion channels mediate a wide variety of physiological processes by forming small pores across the membranes that allow regulated flow of ions into or out of the cell. The primary linear sequences of ion channel proteins, like any proteins, are composed by 20 different amino acids, each of which is determined by specific triplet codon in their genes. Site-directed mutagenesis is a widely used molecular biology method to change the triplet in the coding sequence and thereby the amino acid residue in the protein sequence. Functional characterization of the ion channels carrying point mutations allows us to interrogate the structure-function relationships of the ion channels. Here, we will describe the site-directed mutagenesis procedures, in which the wide-type cDNA or plasmid is used as a template to synthesize the complementary mutation-containing DNAs from two mutagenic primers in the polymerase chain reaction. © 2013 Springer Science+Business Media, LLC.


Fan J.-M.,Zhejiang University | Wang X.,Zhejiang University | Hao K.,Key Laboratory of Medical Neurobiology | Hao K.,Zhejiang University of Science and Technology | And 7 more authors.
Hormones and Behavior | Year: 2013

We previously reported that gestational intermittent hypoxia (GIH) causes anxiety-like behavior in neonatal rats. Here, we showed that the anxiogenic effect was correlated with upregulation of corticotropin-releasing hormone receptor 1 (CRHR1) in the hypothalamic paraventricular nuclei (PVN) by GIH, and was selective to male offspring. The anxiety-like behavior was assessed by both the open field (OF) and elevated plus maze (EPM) tests. We demonstrated that GIH triggered anxiety-like behavior in male offspring, but not in female offspring or in the postpartum dams. Microinjection of antalarmin, a CRHR1-selective antagonist, into the PVN of the male offspring significantly increased the distance traveled and time spent in the central portion of the OF, and the time spent in the open arms in the EPM compared with controls. However, microinjection of the CRHR2 agonist, urocortin III, into the PVN did not affect anxiogenic behavior in the male offspring. These findings clearly demonstrate a gender-selective effect of GIH to increase anxiety-like behavior and this anxiogenic effect might be linked to embryogenically-driven upregulation of PVN CRHR1. © 2012 Elsevier Inc.


Wang X.,Zhejiang University | Wang X.,Key Laboratory of Medical Neurobiology | Shen Y.,Hangzhou Normal University | Chen W.,Zhejiang University | Chen W.,Key Laboratory of Medical Neurobiology
American Journal of Alzheimer's Disease and other Dementias | Year: 2013

Frontotemporal dementia (FTD) is the second most common type of presenile dementia and is the most common form of dementia with the onset before 60 years of age. Its typical symptoms include behavioral disorders, affective symptoms, and language disorders. The FTD is a genetically and pathologically heterogeneous degenerative disorder. Animal models have provided more insights into the pathogenic mechanisms. There are currently no medications that are specifically approved for the treatment of FTD by the Food and Drug Administration. In this article, we review the recent advances in the molecular pathogenesis, pathology, animal models, and therapy for FTD. Better understanding of the pathogenesis and the use of animal models will help develop novel therapeutic strategies and provide new targets for FTD treatment. © The Author(s) 2012.


Fan J.-M.,Zhejiang University | Fan J.-M.,Wenzhou University | Chen X.-Q.,Zhejiang University | Chen X.-Q.,Key Laboratory of Medical Neurobiology | And 6 more authors.
Neuroendocrinology Letters | Year: 2014

OBJECTIVES: To investigate whether CRHR1 and CRHR2 are colocalized in CRH-specific neurons in rat brain. METHODS: Double/triple immunofluorescence, and combined in situ hybridization were performed in the PVN, amygdala and hippocampus, and triple immunofluorescence was applied to the median eminence (ME), dorsal raphe (DR) and locus coeruleus (LC). RESULTS: Both CRHR1 and CRHR2 immunoreactivity were highly coexpressed in the PVN, central nucleus of the amygdala (CeA) and hippocampus. Triple immunofluorescence under confocal microscopy confirmed that CRHR1 and CRHR2 are coexpressed in CRH-producing neurons in these regions. The results of in situ hybridization combined with double immunofluorescence further strengthened the finding that CRHR1 and CRHR2 were coexpressed in CRH-specific neurons in the PVN, CeA and hippocampus. In addition, CRH immunoreactivity signals were evidently distributed in the ME, DR and LC, and were coexpressed with both receptors. CONCLUSION: CRH receptors colocalize in CRH-containing neurons in the PVN, CeA and hippocampus, and CRH, CRHR1, and CRHR2 coexist in the DR and LC. Our results implicate CRHR1 and CRHR2 in coordinating the regulation of CRH neuronal activity in stress and behavioral responses.


He X.,Zhejiang University | He X.,Key Laboratory of Medical Neurobiology | Sun B.-G.,Zhejiang University | Sun B.-G.,Key Laboratory of Medical Neurobiology
Yaoxue Xuebao | Year: 2014

Alzheimer's disease (AD) is a most common neurodegenerative disease. The mechanisms underlying AD, especially late-onset AD, remain elusive. In the past few years, results from genome-wide association studies (GWAS) and systems approaches indicated that innate immune responses mediated by microglia played critical roles in AD. Functional analysis on animal models also showed that immune receptors or proteins expressed in microglia mediated Aβ-induced inflammation, or Aβ phagocytosis by microglia. Microglia plays double sword roles in AD. More work is warranted to elucidate the exact roles of microglia in AD, which will facilitate our better understanding of the mechanisms underlying AD.


Chen W.,Zhejiang University | Yu S.,Zhejiang University | Zhu J.,Zhejiang University | Chai H.,Zhejiang University | And 3 more authors.
Journal of Clinical Neurology (Korea) | Year: 2012

Background and Purpose Chronic tension-type headache (a primary headache disorder) and cervicogenic headache (a secondary headache disorder that is attributable to upper cervical spine pathology) share similar clinical manifestations, but their associated personality traits may differ. We evaluated the personality differences between sufferers of chronic tension-type headache and cervicogenic headache. Methods We administered the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) and the Zuckerman Sensation-Seeking Scale (SSS) to 18 patients suffering from chronic tension-type headache, 19 suffering from cervicogenic headache, and 26 healthy volunteers. Depressive trends were measured with the Plutchik-van-Praag Depression Inventory (PVP). Results Compared to healthy controls, the chronic tension-type headache group scored significantly higher on ZKPQ Neuroticism-Anxiety and on the PVP, while the cervicogenic headache group scored significantly lower on SSS Thrill and Adventure Seeking. In addition, the total SSS score was significantly lower in the cervicogenic headache group than in both the chronic tension-type headache group and the healthy controls. Conclusions The results of this study indicate that higher scores for neuroticism-anxiety and depression were associated with chronic tension-type headache, while lower sensation-seeking scores were associated with cervicogenic headache. © 2012 Korean Neurological Association.


Chen W.,Zhejiang University | Chen W.,Key Laboratory of Medical Neurobiology | Hu J.,Zhejiang University | Hu J.,Key Laboratory of Medical Neurobiology | And 7 more authors.
Psychiatria Danubina | Year: 2014

Background: The effect of the cognitive behavioral therapy (CBT) for panic disorder varies, but how personality disorder functioning style influences it remains unclear. Subjects and methods: In 30 healthy volunteers and 44 patients with panic disorder (22 treated and 22 waiting list), we administered the Parker Personality Measure (PERM) and the Plutchik-van Praag Depression Inventory (PVP). Before and during the CBT or waiting period, patients were asked to record their panic attacks using the Panic Attack Record (PAR). Results: Patients scored significantly higher on PERM Antisocial, Borderline, Histrionic, Avoident, Dependent, and Passive-aggressive styles and on depression. After CBT, all PAR parameters were significantly reduced in the treated group. The Obsessive-compulsive style was positively correlated with the panic attack duration and the total-thought before CBT or waiting period in all patients. In treated patients, the decreased panic attack duration was positively correlated with Histrionic, Obsessive-compulsive and Passive-aggressive; the decreased total symptom number was positively correlated with Antisocial and Histrionic; the decreased total-sensation was positively correlated with antisocial; and the total-thought was positively correlated with Narcissistic style. Conclusions: The length and duration of CBT was short and mainly with behavioral strategies, how personality influenced the related cognition per se remains unknown here. However, our preliminary results indicate that personality disorder functioning styles related to the externalized behaviors and the Obsessive-compulsive style have positive effects on CBT for panic disorder, implying that CBT practitioners should note their personality styles when treating these patients. © Medicinska naklada.

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