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師資隊(duì)伍
徐楠杰
  作者:  2021-03-25

基本信息 >>>

徐楠杰

神經(jīng)細(xì)胞發(fā)育與腦功能失調(diào)研究組

電話:021-34696293

郵箱:[email protected]

英文網(wǎng)頁:Loop | Nan-Jie Xu, https://loop.frontiersin.org/people/321851/overview

地址:上海市黃浦區(qū)重慶南路280號(hào)西5號(hào)樓303

研究方向>>>

研究興趣聚焦認(rèn)知行為相關(guān)的神經(jīng)發(fā)生和突觸發(fā)育以及神經(jīng)退變早期的突觸丟失機(jī)制:

1. 成體神經(jīng)干細(xì)胞靜息和激活轉(zhuǎn)換調(diào)節(jié)

神經(jīng)干細(xì)胞和神經(jīng)前體細(xì)胞參與神經(jīng)環(huán)路的維持和更新,。我們發(fā)現(xiàn)自主運(yùn)動(dòng)等外界刺激能夠促進(jìn)海馬齒狀回神經(jīng)元活動(dòng)增強(qiáng),,改變神經(jīng)干細(xì)胞微環(huán)境進(jìn)而使靜息態(tài)神經(jīng)干細(xì)胞激活,加速神經(jīng)干細(xì)胞的增殖分化和神經(jīng)元的新生(Sci Adv 2019),。我們致力于解析成體神經(jīng)干細(xì)胞靜息態(tài)和激活態(tài)的轉(zhuǎn)換機(jī)制,,并闡明環(huán)境刺激對新生神經(jīng)元細(xì)胞及功能性突觸形成的調(diào)節(jié)作用,。

2. 發(fā)育期行為的突觸發(fā)生和環(huán)路形成

發(fā)育期情感和認(rèn)知相關(guān)行為的產(chǎn)生需要特異神經(jīng)元連接和突觸的形成。我們揭示了海馬CA1和杏仁核的興奮性神經(jīng)元的早期突觸形成介導(dǎo)先天性恐懼的產(chǎn)生的機(jī)制(Nat Commun 2016; J Neurosci 2016),,進(jìn)一步發(fā)現(xiàn)海馬DG-CA3區(qū)突觸是發(fā)育期動(dòng)物產(chǎn)生最早的社交識(shí)別記憶的結(jié)構(gòu)基礎(chǔ)(J Cell Biol 2018; Mol Psychiatry 2021),,發(fā)育期的社交行為促進(jìn)長期記憶的突觸維持并拮抗遺忘的發(fā)生(Transl Psychiatry 2020)。我們還解析了啟動(dòng)社交行為的前額葉皮層重要細(xì)胞和分子機(jī)制(PNAS 2023),。我們探索大腦發(fā)育過程中長距離神經(jīng)環(huán)路如何通過連接整合外界信號(hào)到腦內(nèi)的認(rèn)知和情感關(guān)鍵核團(tuán),,以及這些核團(tuán)之間如何形成突觸,進(jìn)而介導(dǎo)社交,,情緒,,獎(jiǎng)賞等行為的產(chǎn)生。

3. 神經(jīng)退行性病變早期的突觸丟失機(jī)制

阿爾茨海默?。?span lang="EN-US">AD)的大腦神經(jīng)元功能異常遠(yuǎn)早于典型病理特征的出現(xiàn),。我們發(fā)現(xiàn)輕度認(rèn)知損傷發(fā)生時(shí)初期神經(jīng)元胞內(nèi)鈣失衡和突觸丟失是引發(fā)晚期記憶障礙的重要原因(Transl Neurodegener 2020; J Clin Invest 2022)。我們利用家族性AD模型,,研究疾病早期病理微環(huán)境因素和胞內(nèi)鈣穩(wěn)態(tài)之間的重要調(diào)節(jié)關(guān)系,,深入解析引發(fā)重要核團(tuán)內(nèi)神經(jīng)元退變和突觸丟失的關(guān)鍵分子機(jī)制。

個(gè)人簡歷 >>>

徐楠杰,,特聘教授,、研究員、博士生導(dǎo)師,,解剖學(xué)與生理學(xué)系執(zhí)行主任,。入選國家高層次人才特支計(jì)劃科技創(chuàng)新領(lǐng)軍人才、上海市科委優(yōu)秀學(xué)術(shù)帶頭人,、國家海外高層次青年人才計(jì)劃,。兼任中國細(xì)胞生物學(xué)學(xué)會(huì)理事、神經(jīng)細(xì)胞生物學(xué)分會(huì)會(huì)長,、中國神經(jīng)科學(xué)學(xué)會(huì)神經(jīng)發(fā)育與再生分會(huì)委員、上海市衰老和退行性疾病分會(huì)常務(wù)理事、上海市神經(jīng)科學(xué)學(xué)會(huì)理事,。實(shí)驗(yàn)室研究方向集中在神經(jīng)突觸發(fā)育和神經(jīng)退行性病變,。

科研項(xiàng)目 >>>

1.科技創(chuàng)新2030—“腦科學(xué)與類腦研究”重大項(xiàng)目子課題:本能情緒相關(guān)腦區(qū)神經(jīng)元集群和神經(jīng)環(huán)路(2021-2026

2.國家自然科學(xué)基金重點(diǎn)項(xiàng)目:出生后發(fā)育期社交行為的突觸發(fā)生和環(huán)路形成機(jī)制(2021-2025

3.國家自然科學(xué)基金面上項(xiàng)目:阿爾茨海默病早期異常情感表征和認(rèn)知環(huán)路調(diào)節(jié)機(jī)制(2019 -2022

4.國家自然科學(xué)基金面上項(xiàng)目:PDZ蛋白Lnx1介導(dǎo)的海馬神經(jīng)環(huán)路發(fā)育和可塑性機(jī)制 (2017-2020

5.國家重點(diǎn)基礎(chǔ)研究發(fā)展計(jì)劃(973項(xiàng)目子課題):調(diào)控前腦神經(jīng)祖細(xì)胞發(fā)育過程的微環(huán)境解析(2014-2018

6.國家自然科學(xué)基金面上項(xiàng)目:EphB受體信號(hào)介導(dǎo)的神經(jīng)干細(xì)胞分化機(jī)制(2014-2017

7.國家自然科學(xué)基金重大研究計(jì)劃培育項(xiàng)目:Eph-ephrin受體信號(hào)介導(dǎo)的情感和記憶相關(guān)神經(jīng)環(huán)路的發(fā)育機(jī)制(2013-2015

8.國家自然科學(xué)基金面上項(xiàng)目:神經(jīng)軸突剪切的Eph-ephrin雙向信號(hào)轉(zhuǎn)導(dǎo)(2013

論文與專著 >>>

1.He LN (何麗娜), Chen S, Yang Q, Wu Z, Lao ZK, Tang CF, Song JJ, Liu XD, Lu J, Xu XH, Chen JJ, Xu TL, Sun S*, Xu NJ*. EphB2 dependent prefrontal cortex activation promotes long-range social approach and partner responsiveness. Pro Nat Acad Sci U S A, 120(9): e2219952120 (2023).

2.Zou HY (鄒浩玉)#, Guo L (郭霖)#, Zhang B#, Chen S, Wu XR, Liu XD, Xu XY, Li BY, Chen SD, Xu NJ*, Sun S*. Aberrant miR-339-5p/neuronatin signaling causes prodromal neuronal calcium dyshomeostasis in mutant presenilin mice. J Clin Invest, 132(8): e149160 (2022).

3.Liu XD (劉賢東)#, Ai PH (艾鵬輝)#, Zhu XN, Pan YB, Halford MM, Henkemeyer M, Feng DF, Xu TL, Sun S*, Xu NJ*. Hippocampal Lnx1-NMDAR multi-protein complex mediates initial social memory. Mol Psychiatry, 26:3956–3969 (2021).

4.Xu M (徐淼), Zhu JY, Liu XD, Luo MY, Xu NJ*. Roles of physical exercise in neurodegeneration: reversal of epigenetic clock. Transl Neurodegener, 10:30 (2021). (Review)

5.Wu XR (吳欣蓉)#, Zhang Y (張?jiān)?/span>)#, Liu XD, Han WB, Xu NJ*, Sun S*. EphB2 mediates social isolation-induced memory forgetting. Transl Psychiatry, 10:389 (2020).

6.Ai PH (艾鵬輝)#, Chen S (陳偲)#, Liu XD, Zhu XN, Pan YB, Feng DF, Chen SD, Xu NJ*, Sun S*. Paroxetine ameliorates prodromal emotional dysfunction and late-onset memory deficit in Alzheimer’s disease mice. Transl Neurodegener, 9:18 (2020).

7.Dong J (董健), Pan YB, Wu XR, He LN, Liu XD, Feng DF, Xu TL, Sun S*, Xu NJ*. A neuronal molecular switch through cell-cell contact that regulates quiescent neural stem cells. Sci Adv, 5: eaav4416 (2019).

8.Liu XD (劉賢東), Zhu XN, Halford MM, Xu TL, Henkemeyer M, Xu NJ*. Retrograde regulation of mossy fiber axon targeting and terminal maturation via postsynaptic Lnx1. J Cell Biol, 217: 4007-4024 (2018).

9.Zhu XN (朱曉娜), Liu XD, Zhuang H, Henkemeyer M, Yang JY*, Xu NJ*. Amygdala EphB2 signaling regulates glutamatergic neuron maturation and innate fear. J Neurosci, 36(39):10151-10162 (2016).

10.Zhu XN (朱曉娜), Liu XD, Sun S*, Zhuang H, Yang JY, Henkemeyer M, Xu NJ*. Ephrin-B3 mediates timed axon targeting and amygdala spinogenesis for innate fear behaviour. Nat Commun, 7:11096 (2016).

11.Xu NJ, Sun S, Gibson J and Henkemeyer M*. A dual shaping mechanism for postsynaptic ephrin-B3 as a receptor that sculpts dendrites and synapses. Nat Neurosci, 14: 1421-1429 (2011).

12.Xu NJ, Henkemeyer M*. Ephrin-B3 reverse signaling through Grb4 and downstream cytoskeletal regulators mediates axon pruning. Nat Neurosci, 12: 268-276 (2009).

13.Xu NJ, Yu YX, Zhu JM, Liu H, Shen L, Zen R, Zhang X, Pei G*. Inhibition of SNAP-25 phosphorylation at Ser187 is involved in chronic morphine-induced down-regulation of SNARE complex formation. J Biol Chem, 279: 40601-8 (2004).

14.Xu NJ, Bao L, Fan HP, Bao GB, Pu L, Lu YJ, Wu CF, Zhang X*, Pei G*. Morphine withdrawal increases neuronal glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses. J Neurosci, 23: 4775-4784 (2003).