發(fā)布時(shí)間：2018-05-05 13:08

  本文選題：MGE + nNOS��； 參考：《南京醫(yī)科大學(xué)》2017年碩士論文

【摘要】：皮層與海馬的信息處理依賴于谷氨酸能興奮性投射神經(jīng)元與γ-氨基丁酸(GABA)能抑制性神經(jīng)元之間復(fù)雜的相互作用。兩種神經(jīng)元之間協(xié)調(diào)的相互作用對(duì)于維持大腦興奮與抑制信號(hào)之間微妙的平衡關(guān)系至關(guān)重要,這種平衡受到很多神經(jīng)調(diào)節(jié)物質(zhì)如不同的神經(jīng)肽、一氧化氮(NO)等的動(dòng)態(tài)調(diào)節(jié)。平衡的破壞會(huì)導(dǎo)致很多病理性的障礙如癲癇、自閉癥、精神分裂癥等。NO參與了神經(jīng)傳遞、突觸可塑性、血管舒張、炎癥等很多生理過程,是一個(gè)非常重要的信號(hào)分子,NO產(chǎn)生或釋放功能的缺陷會(huì)導(dǎo)致神經(jīng)元死亡以及癲癇等疾病。NO由一氧化氮合酶(NOS)合成,根據(jù)最初被發(fā)現(xiàn)時(shí)所在的部位,NOS又可分為內(nèi)皮型一氧化氮合酶(eNOS)、神經(jīng)元型一氧化氮合酶(nNOS)以及可誘導(dǎo)型一氧化氮合酶(iNOS)。在神經(jīng)元中NO主要由nNOS合成,在幼稚和成熟的海馬與皮層中nNOS主要表達(dá)在GABA能中間神經(jīng)元上。GABA能中間神經(jīng)元主要來源于三個(gè)不同部位:中間神經(jīng)節(jié)隆起(MGE)、外側(cè)/尾部神經(jīng)節(jié)隆起(LGE/CGE)以及視前區(qū)(POA),每個(gè)神經(jīng)上皮前體細(xì)胞部位都會(huì)產(chǎn)生不同的中間神經(jīng)元亞型。通過在轉(zhuǎn)基因鼠上運(yùn)用遺傳譜系追蹤技術(shù)發(fā)現(xiàn),皮層I型nNOS主要來源于MGE,II型nNOS則是MGE、LGE/CGE以及POA的混合來源,也就意味著皮層大部分的nNOS來源于MGE。MGE細(xì)胞移植到成年鼠的腦內(nèi)可以擴(kuò)散、遷移并且分化成GABA—主要的抑制性神經(jīng)遞質(zhì)。很多假說認(rèn)為移植MGE的前體細(xì)胞可以增加局部的抑制,運(yùn)用于臨床治療具有非常重要的意義。近幾年來分離、移植MGE來源的中間神經(jīng)元前體細(xì)胞方面研究有很多,皮質(zhì)中間神經(jīng)元的前體細(xì)胞移植到一系列的中樞神經(jīng)系統(tǒng)組織后可以廣泛的遷移并且與宿主神經(jīng)元網(wǎng)絡(luò)形成突觸聯(lián)系。MGE細(xì)胞移植后可以進(jìn)行整合的能力被廣泛運(yùn)用到細(xì)胞療法上,從而治療一系列中樞神經(jīng)系統(tǒng)疾病:癲癇、神經(jīng)性疼痛、帕金森以及阿爾茲海默病等。因此運(yùn)用MGE前體細(xì)胞進(jìn)行的細(xì)胞移植在治療神經(jīng)和精神疾病中是一個(gè)非常有潛能的臨床途徑�？謶质且环N與適應(yīng)能力相關(guān)的基本情緒,是面對(duì)外界可知或不可知的威脅時(shí)激發(fā)的學(xué)習(xí)能力。適度的恐懼反應(yīng)能警示動(dòng)物面對(duì)類似于先前經(jīng)歷的有害環(huán)境,及時(shí)評(píng)估潛在的危險(xiǎn)并做出保護(hù)反應(yīng),而病理性恐懼記憶的產(chǎn)生將會(huì)導(dǎo)致創(chuàng)傷后應(yīng)激綜合征(posttraumatic stress disorder,PTSD)、驚恐障礙(panic disorder)、恐懼癥(phobia)等恐懼相關(guān)疾病�；诎透β宸驐l件反射原理建立的經(jīng)典的條件性恐懼(Cued-fear conditioning)以及在此基礎(chǔ)上發(fā)展出的背景關(guān)聯(lián)恐懼(Contextual fear conditioning)是最常見研究恐懼相關(guān)疾病的動(dòng)物模型,廣泛應(yīng)用于恐懼學(xué)習(xí)和記憶的神經(jīng)、分子機(jī)制研究。海馬是大腦邊緣系統(tǒng)結(jié)構(gòu)之一,在情感和認(rèn)知功能中具有重要作用。既往研究表明,海馬與PTSD發(fā)生、發(fā)展及治療密切相關(guān),海馬DG區(qū)是認(rèn)知功能和情緒調(diào)控的神經(jīng)基礎(chǔ),包含DG區(qū)的海馬三突觸通路對(duì)于背景關(guān)聯(lián)型恐懼記憶至關(guān)重要。由于目前對(duì)于nNOS前體細(xì)胞來源鮮有報(bào)道,且大部分研究著眼于皮層nNOS細(xì)胞。因此,我們希望能通過培養(yǎng)MGE細(xì)胞來研究nNOS。本課題設(shè)計(jì)研究三部分內(nèi)容:1)通過培養(yǎng)不同部位前體細(xì)胞來確證nNOS細(xì)胞最主要的胚胎來源是MGE,并改進(jìn)獲取MGE的方法,從而獲得狀態(tài)較好的nNOS細(xì)胞;2)對(duì)nNOS細(xì)胞進(jìn)行體外培養(yǎng)與鑒定,并嘗試多種方法來提高其中nNOS細(xì)胞的比例;3)將較高nNOS比例的MGE前體細(xì)胞體外培養(yǎng)成神經(jīng)球,并移植到海馬DG區(qū),研究nNOS細(xì)胞以及GABA能中間神經(jīng)元在小鼠恐懼記憶獲得中發(fā)揮的作用。第一部分為了探究nNOS的胚胎來源,結(jié)合已有的文獻(xiàn)報(bào)導(dǎo)以及對(duì)不同時(shí)間點(diǎn)nNOS陽(yáng)性率的研究,我們選取了 E12.5的胎仔,在體視顯微鏡下取其整腦,并于多聚甲醛中固定24h,隨后蔗糖梯度脫水6天后進(jìn)行冠狀冰凍切片,并于載玻片上貼片免疫組化,用免疫標(biāo)記物PAX6、FOXG-1、Meis-2、Nkx2.1分別標(biāo)記皮層、前腦、LGE和MGE,對(duì)E12.5天胚胎各個(gè)部位的形態(tài)及范圍有個(gè)確切的認(rèn)識(shí)。此后,我們就進(jìn)行E12.5天胎仔的原代培養(yǎng),在體視顯微鏡下,分離出同一只胎仔的皮層、POA、CGE、LGE和MGE,體外培養(yǎng)10天后,通過細(xì)胞免疫組化鑒定其中nNOS細(xì)胞的比例,發(fā)現(xiàn)MGE部位nNOS細(xì)胞比例最高,即確證了 MGE是nNOS細(xì)胞主要的胚胎來源。由于MGE細(xì)胞獲取方法以及分離的時(shí)間長(zhǎng)短均會(huì)影響原代培養(yǎng)后細(xì)胞的狀態(tài),因此我們希望能夠通過改進(jìn)現(xiàn)有的MGE獲取方法,使得原代培養(yǎng)后的細(xì)胞狀態(tài)更好。綜合對(duì)比多種方法后,我們嘗試了瓊脂糖凝膠包埋整腦后Chopper冠狀切片、緩沖液中分離MGE的方法以及體視顯微鏡下于緩沖液中直接分離MGE的方法,后者無論是操作時(shí)長(zhǎng)、細(xì)胞狀態(tài)以及nNOS細(xì)胞陽(yáng)性率均優(yōu)于前者。因此第一部分的實(shí)驗(yàn),我們確定了 MGE是nNOS細(xì)胞主要的胚胎來源,并通過對(duì)比改進(jìn)了 MGE獲取的方法,便于之后的研究。第二部分為了了解MGE來源的nNOS細(xì)胞的形態(tài)和性質(zhì),我們進(jìn)行了E12.5天胎仔的原代培養(yǎng),10天后通過免疫組化進(jìn)行了 nNOS細(xì)胞鑒定。發(fā)現(xiàn)培養(yǎng)的MGE細(xì)胞中90%為GAD67+細(xì)胞,99.97%為Tuj-1+細(xì)胞,大部分的nNOS細(xì)胞可以與GAD67共標(biāo),但也有部分nNOS細(xì)胞是GAD67陰性的。由于MGE細(xì)胞大部分是GABA能中間神經(jīng)元,且在體能分化形成各種亞型,鑒于體外培養(yǎng),因此我們也進(jìn)行了其它亞型的鑒定,發(fā)現(xiàn)體外培養(yǎng)的MGE細(xì)胞中確實(shí)有表達(dá)生長(zhǎng)抑素(somatostatin,SST)、小清蛋白(parvalbumin,PV)、鈣結(jié)合蛋白(Calbindin,CB)、鈣網(wǎng)膜蛋白(Calretinin,CR)等其它亞型的中間神經(jīng)元。體外培養(yǎng)的nNOS細(xì)胞形態(tài)多樣,大小不一,且同一玻片上免疫組化的熒光強(qiáng)度也有所差別。由于體外培養(yǎng)的nNOS細(xì)胞陽(yáng)性率較低,因此我們嘗試了多種方法來提高其中nNOS的比例。結(jié)果表明選取MGE不同部位以及神經(jīng)營(yíng)養(yǎng)因子(NGF)的誘導(dǎo)并不能提高nNOS細(xì)胞的陽(yáng)性率。而在不同胚胎期(E11.5-E14)分離MGE,胚胎以及MGE的大小和形態(tài)有很大的差別。其中nNOS比例確有差異,E12.5天陽(yáng)性率最高,其次是E13天。結(jié)果表明MGE來源的nNOS經(jīng)過體外培養(yǎng),其細(xì)胞形態(tài)以及性質(zhì)與體內(nèi)培養(yǎng)差異不大,且E12.5天獲取的MGE細(xì)胞nNOS比例最高。第三部分為了進(jìn)一步探索MGE來源的nNOS在小鼠背景關(guān)聯(lián)型近期恐懼記憶獲得中所扮演的角色,我們首先將體外培養(yǎng)3天成神經(jīng)球的GFP鼠的MGE細(xì)胞濃縮,并通過玻璃導(dǎo)管注射到野生型鼠海馬DG區(qū),移植2個(gè)月后與注射GFP鼠的MGE死細(xì)胞相比較,發(fā)現(xiàn)野生型鼠中移植MGE細(xì)胞并沒有恐懼記憶獲得值的改變。接下來,我們又將GFP鼠MGE神經(jīng)球移植到nNOS--鼠海馬DG區(qū),與注射死細(xì)胞相比,發(fā)現(xiàn)nNOS--鼠移植GFP+MGE細(xì)胞后,其背景關(guān)聯(lián)型近期恐懼記憶獲得顯著提高,且nNOS-/-鼠不論雌雄。以上結(jié)果表明,野生型鼠海馬DG區(qū)移植MGE細(xì)胞,背景關(guān)聯(lián)型近期恐懼記憶造模后,其恐懼獲得的學(xué)習(xí)能力無改善,而nNOS-/-鼠海馬DG區(qū)移植MGE細(xì)胞,造模后,不論雌雄,其獲得恐懼記憶的學(xué)習(xí)能力提高。為了進(jìn)一步探究MGE細(xì)胞對(duì)nNOS-/-鼠行為學(xué)的改善作用是否由MGE來源的nNOS細(xì)胞主導(dǎo)。我們?nèi)6或nNOS-/-鼠的MGE細(xì)胞,體外培養(yǎng)3天成球后濃縮液轉(zhuǎn)染GFP病毒1.5小時(shí),然后懸瓶培養(yǎng)4-6天后,將神經(jīng)球移植到nNOS-/-鼠海馬DG區(qū)。2個(gè)月后,發(fā)現(xiàn)移植B6和nNOS--鼠的MGE對(duì)比,nNOS-/-鼠恐懼記憶獲得值沒有改變,且與宿主的性別無關(guān)。為了確證,我們又選取了雌性nNOS-/-鼠進(jìn)行分析,結(jié)果表明nNOS-/-鼠移植B6鼠的MGE與移植死細(xì)胞相比,獲得值增加,nNOS--鼠移植nNOS-/-鼠的MGE與移植死細(xì)胞相比,獲得值也增加,但nNOS-/-鼠移植B6或nNOS-/-鼠的MGE細(xì)胞之間無差異。以上結(jié)果表明nNOS-/-鼠移植MGE后恐懼記憶學(xué)習(xí)能力的提高源于MGE細(xì)胞中非nNOS的其它GABA能中間神經(jīng)元。結(jié)論:(1)MGE是nNOS細(xì)胞主要的胚胎來源,并通過對(duì)比改進(jìn)了 MGE獲取的方法,便于之后的研究(2)MGE來源的nNOS經(jīng)過體外培養(yǎng),其細(xì)胞形態(tài)以及性質(zhì)與體內(nèi)細(xì)胞差異不大,且E12.5天獲取的MGE細(xì)胞nNOS比例最高。(3)野生型鼠海馬DG區(qū)移植MGE細(xì)胞,背景關(guān)聯(lián)型近期恐懼記憶造模后,其恐懼獲得的學(xué)習(xí)能力無改善,而nNOS-/-鼠海馬DG區(qū)移植MGE細(xì)胞,造模后,不論雌雄,其獲得恐懼記憶的學(xué)習(xí)能力提高。nNOS-/-鼠移植MGE后恐懼記憶學(xué)習(xí)能力的提高源于MGE細(xì)胞中非nNOS的其它GABA能中間神經(jīng)元。
[Abstract]:The information processing of the cortex and hippocampus depends on the complex interaction between glutamate excitatory and gamma aminobutyric acid (GABA) suppressor neurons. The coordinated interaction between the two neurons is essential to maintain a delicate balance between the brain's excitatory and inhibitory signals, which is affected by many nerves. Regulatory substances such as different neuropeptides, nitric oxide (NO) and other dynamic regulation. Balance damage can lead to many pathological disorders such as epilepsy, autism, schizophrenia, etc..NO participates in many physiological processes, such as neurotransmission, synaptic plasticity, vasodilatation, and inflammation, is a very important signal molecule, NO production or release function. Defects, such as neuronal death and epilepsy, are synthesized by nitric oxide synthase (NOS), and NOS can be divided into endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS), according to the site where it was originally found. In neurons, NO is synthesized mainly by nNOS in the neuron. In the neuron, the.NO is synthesized in the neuron. The immature and mature hippocampal and cortex nNOS are mainly expressed in the middle neurons of the GABA energy intermediate neurons mainly from three different sites: the middle ganglion bulge (MGE), the lateral / tail ganglion bulge (LGE/CGE) and the preoptic region (POA), and each of the neurons of the preoptic nerve progenitor cells produce different intermediate neurons. By using genetic lineage tracking technique on transgenic mice, the cortical I type nNOS is mainly derived from MGE, and II nNOS is a mixed source of MGE, LGE/CGE, and POA, which means that the majority of the nNOS originates from the transplantation of MGE.MGE cells to the brain of adult mice, and migrates and differentiates into GABA major inhibitory gods. There are many hypotheses that transplantation of MGE's precursor cells can increase local inhibition and is of great significance in clinical treatment. In recent years, there have been many studies on the transplanting of MGE derived intermediate neurons in the precursor cells, and the precursor cells of the cortical neurons were transplanted into a series of central nervous system tissues. The ability to undergo extensive migration and to form synaptic connections with the host network of.MGE cells can be widely applied to cell therapy to treat a series of central nervous system diseases: epilepsy, neuropathic pain, Parkinson and Alzheimer's disease, and so on the use of MGE precursor cells Transplantation is a very potential clinical pathway in the treatment of neurological and mental diseases. Fear is a basic emotion associated with adaptation. It is a learning ability that is stimulated in the face of an outside known or unknowable threat. A moderate fear response can warn the animal to face the harmful environment similar to the previous experience and assess the potential in time. Dangerous and protective reactions, and the formation of pathological fear memory will cause posttraumatic stress disorder (PTSD), panic disorder (panic disorder), phobia (phobia) and other phobia related diseases. The classical conditioned fear based on Pavlov conditioned reflex (Cued-fear conditioning) is based on the classical conditioned fear (Cued-fear conditioning). Contextual fear conditioning, developed on this basis, is the most common animal model for studying fear related diseases. It is widely used in the study of nervous and molecular mechanisms of fear learning and memory. The hippocampus is one of the structure of the cerebral marginal system and plays an important role in emotional and cognitive functions. Previous studies have shown that The hippocampus is closely related to the occurrence, development and treatment of PTSD. The hippocampal DG area is a neural basis for cognitive and emotional regulation. The hippocampal three synaptic pathway, including the DG region, is essential for the background associated fear memory. Since there are few reports on the source of nNOS precursor cells, and most of the studies focus on the cortical nNOS cells. We hope to study the three parts of the design and research of nNOS. based on the cultivation of MGE cells: 1) to confirm that the most important embryonic source of nNOS cells by cultivating different parts of the precursor cells is MGE, and improves the method of obtaining MGE to obtain the better nNOS cells; 2) to culture and identify the nNOS cells in vitro, and to try a variety of methods. To improve the proportion of nNOS cells; 3) the MGE precursor cells of higher nNOS ratio were cultured into nerve spheres in vitro and transplanted into the hippocampal DG region to study the role of nNOS cells and GABA intermediate neurons in the acquisition of fear memory in mice. The first part was to explore the embryonic fetal origin of nNOS, combined with the existing literature and the difference. In the study of the time point nNOS positive rate, we selected the E12.5 fetus, took the whole brain under the stereoscopic microscope, and fixed the 24h in the paraformaldehyde, then the coronary frozen section was followed by 6 days after the sucrose gradient dehydration, and the patch was immunohistochemistry on the slides. The immune markers, PAX6, FOXG-1, Meis-2, and Nkx2.1 were used to mark the cortex, the forebrain, LGE and MGE respectively. There is a definite understanding of the morphology and scope of each part of the E12.5 day embryo. After that, we carried out the primary culture of the E12.5 day fetus. Under the stereoscopic microscope, we isolated the same fetus' cortex, POA, CGE, LGE and MGE. After 10 days in vitro culture, the proportion of nNOS cells was identified by cellular immunization, and nNOS cells in MGE site were found. The highest proportion, that is, confirmed that MGE is the main source of nNOS cells. Because the method of obtaining MGE cells and the length of separation will affect the state of the cells after primary culture, we hope that we can improve the existing MGE methods to make the cells in the primary culture better. The Chopper coronal section of the whole brain after the agarose gel was embedded in the agarose gel, the method of separating MGE in the buffer solution and the method of direct separation of MGE under the stereoscopic microscope in the buffer solution were tried. The latter was superior to the former in the length of operation, the cell state and the positive rate of the nNOS cells. Therefore, the first part of the experiment confirmed that MGE was the main nNOS cell master. In order to understand the morphology and properties of nNOS cells from MGE sources, the second part, in order to understand the morphology and properties of nNOS cells from MGE sources, carried out the primary culture of E12.5 day fetus and identified the nNOS cells by immunohistochemistry. 90% of the cultured MGE cells were GAD67+ cells, 99.97 were found to be GAD67+ cells, and 99.97 were found to be GAD67+ cells. % of Tuj-1+ cells, most of the nNOS cells can be co labeled with GAD67, but also some of the nNOS cells are GAD67 negative. Since most of the MGE cells are GABA in the intermediate neurons, and in the physical differentiation to form a variety of subtypes, in vitro culture, we have also conducted other subtypes of identification, found in the culture of MGE cells in vitro indeed. Expression of somatostatin (SST), parvalbumin (PV), calcium binding protein (Calbindin, CB), calcalum (Calretinin, CR) and other subtypes of intermediate neurons. The morphology of nNOS cells in vitro is diverse and different in size, and the fluorescence intensity of the same slide is also different. In vitro culture of nNOS. The positive rate of cells was low, so we tried a variety of methods to improve the proportion of nNOS. The results showed that the selection of different parts of MGE and the induction of neurotrophic factor (NGF) did not improve the positive rate of nNOS cells. And there was a great difference between the size and morphology of the embryo and MGE in the different embryo period (E11.5-E14) and the size and morphology of MGE. The positive rate of E12.5 days was the highest, followed by E13 days. The results showed that the MGE source nNOS had little difference in cell morphology and nature from the body culture in vitro, and the nNOS ratio of MGE cells obtained on E12.5 days was the highest. The third part was to further explore the short-term fear memory of MGE derived nNOS in mouse background associated type. In order to get the role, we first concentrated the MGE cells of the GFP rat of the 3 day adult nerve bulb in vitro, and injected it into the hippocampal DG area of the wild rat through a glass catheter. After 2 months, we compared the MGE dead cells of the GFP mice. We found that the transplanted MGE cells in the wild mice did not have a change of fear memory. We also transplanted the GFP rat MGE nerve ball into the DG region of the hippocampus of nNOS-- mice. Compared with the injected dead cells, it was found that after the nNOS-- mice transplanted to GFP+MGE cells, the background associated type of fear memory was significantly improved, and the nNOS-/- mice were male and female. The results showed that the MGE cells in the hippocampal DG area of the wild rat were transplanted and the background associated model of the short-term fear memory model was built. The learning ability of the hippocampal DG region of nNOS-/- rats was not improved, and the transplantation of MGE cells in the DG region of the hippocampus of the rat was improved. To further explore whether the effect of MGE cells on the behavioral learning of nNOS-/- rats was dominated by nNOS cells from MGE sources, we took B6 or nNOS-/- mouse MGE cells in vitro. After 3 days of culture, the concentration solution was transfected to GFP virus for 1.5 hours, and then cultured for 4-6 days after suspension bottle culture, after transplantation of the nerve ball to the nNOS-/- rat hippocampus DG area for.2 months, the MGE contrast between the transplanted B6 and nNOS-- mice was found to be unchanged, and it was not related to the sex of the host. In order to confirm, we also selected female nNOS-/- mice. The results showed that the MGE of the transplanted B6 mice of the nNOS-/- mice increased in comparison with the transplanted dead cells. The MGE of the nNOS-- mice transplanted to the nNOS-/- mice increased as compared with the transplanted dead cells, but there was no difference between the nNOS-/- mice and the MGE cells of the B6 or nNOS-/- mice. The above results showed that the learning ability of fear memory in nNOS-/- mice after the transplant MGE was improved. It is derived from other GABA intermediate neurons of non nNOS in MGE cells. Conclusion: (1) MGE is the main embryonic source of nNOS cells, and the method of MGE obtained by comparison is improved to facilitate the subsequent study (2) the nNOS of MGE source is cultured in vitro, and its cell morphology and properties are not very different from the cells in the body, and the nNOS ratio of MGE cells obtained by E12.5 days is obtained. (3) (3) the transplantation of MGE cells in the hippocampal DG region of the wild rat, the learning ability of fear acquisition was not improved after the background related recent fear memory model, and the transplantation of MGE cells in the DG region of the nNOS-/- rat hippocampus, regardless of the male and female, obtained the learning ability of the fear memory to raise the source of the learning ability of the fear memory learning after the.NNOS-/- mice transplanted to MGE. In MGE cells, non nNOS other GABA interneurons.

【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R749

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 丁曉勇,朱世柱,薛敬玲,孟楊,王紀(jì),高忠慶;牙髓牙本質(zhì)復(fù)合體的nNOS陽(yáng)性神經(jīng)纖維[J];武漢大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2002年04期

2 涂麗莉,馮定慶,齊威琴,徐勝春;人胎海馬內(nèi)nNOS神經(jīng)元的形態(tài)學(xué)觀察[J];中國(guó)組織化學(xué)與細(xì)胞化學(xué)雜志;2005年02期

3 宋志宇;盧宏;孫玉華;魏建科;譚巖;方艷秋;;血管性癡呆大鼠腦內(nèi)超微結(jié)構(gòu)變化及生長(zhǎng)抑素和nNOS的表達(dá)[J];中國(guó)老年學(xué)雜志;2009年18期

4 趙昱,李莉,馬洪駿,羅波,李陳莉,王慧娟;大鼠局灶性腦缺血再灌注中nNOS來源的NO對(duì)細(xì)胞凋亡的影響[J];中國(guó)組織化學(xué)與細(xì)胞化學(xué)雜志;2005年04期

5 余菁;沈偉哉;郭國(guó)慶;;自發(fā)性高血壓大鼠中腦導(dǎo)水管周圍灰質(zhì)nNOS陽(yáng)性神經(jīng)元的變化[J];解剖學(xué)研究;2009年05期

6 穆長(zhǎng)征;王小梅;劉霞;包翠芬;;胚胎小鼠腎發(fā)育過程中nNOS的表達(dá)[J];中國(guó)體視學(xué)與圖像分析;2011年02期

7 ;Alterations in nNOS-containing nerve fibers in corpus cavernosum of spontaneous hypertension rats[J];Asian Journal of Andrology;2003年02期

8 胡向陽(yáng);;醒腦合劑對(duì)急性CO中毒模型小鼠海馬nNOS蛋白表達(dá)的影響[J];河南中醫(yī)學(xué)院學(xué)報(bào);2006年01期

9 南娟;劉慧慧;杜艷霞;邢偉;蔡葵;蔡原;劉鵬;劉玉麗;時(shí)利德;;出生前后鋁暴露對(duì)大鼠學(xué)習(xí)記憶及海馬NO、nNOS的影響[J];中國(guó)藥理學(xué)通報(bào);2007年09期

10 閆蓓,李積勝,汪超,張玉和,何煒;染鉛早期大鼠海馬各區(qū)NOS和nNOS陽(yáng)性神經(jīng)元的變化[J];衛(wèi)生研究;2002年06期

相關(guān)會(huì)議論文 前10條

1 ;Down Regulation of nNOS Activity by PMCA4 via PDZ Domain-dependent Protein-protein Interactions[A];第十一次中國(guó)生物物理學(xué)術(shù)大會(huì)暨第九屆全國(guó)會(huì)員代表大會(huì)摘要集[C];2009年

2 胡向陽(yáng);鄭紹周;;醒腦合劑對(duì)急性CO中毒模型小鼠海馬nNOS蛋白表達(dá)的影響[A];第八次全國(guó)中西醫(yī)結(jié)合虛證與老年醫(yī)學(xué)學(xué)術(shù)研討會(huì)論文集[C];2005年

3 康定鑫;曾因明;;M_5受體參與激活腹側(cè)背蓋區(qū)和伏隔核nNOS表達(dá)[A];2004年浙江省麻醉學(xué)學(xué)術(shù)年會(huì)論文匯編[C];2004年

4 李梅;王林;程驍;周麗華;;nNOS基因調(diào)控發(fā)育期小腦顆粒細(xì)胞神經(jīng)元生長(zhǎng)的體外研究[A];2008年神經(jīng)內(nèi)分泌暨神經(jīng)免疫內(nèi)分泌學(xué)術(shù)研討會(huì)論文摘要匯編[C];2008年

5 ;The expression of postsynaptic density-95 after spinal cord and sciatic nerve injury in rats[A];Proceedings of the 7th Biennial Meeting and the 5th Congress of the Chinese Society for Neuroscience[C];2007年

6 李英慧;趙彥艷;;p300催化的NF-kB乙�；趎NOS基因轉(zhuǎn)錄調(diào)控中的作用[A];第八次全國(guó)醫(yī)學(xué)遺傳學(xué)學(xué)術(shù)會(huì)議(中華醫(yī)學(xué)會(huì)2009年醫(yī)學(xué)遺傳學(xué)年會(huì))論文摘要匯編[C];2009年

7 ;Developmental regulation of PSD-95 and nNOS expression in lumbar spinal cord of rats[A];Proceedings of the 8th Biennial Conference of the Chinese Society for Neuroscience[C];2009年

8 Qi-Gang Zhou;Yao Hu;Jing Zhang;Li-Juan Zhu;Chen Chen;Dan-Lian Wu;Chun-Xia Luo;Dong-Ya Zhu;;Hippocampal nNOS and depression/anxiety behaviors[A];中國(guó)神經(jīng)科學(xué)學(xué)會(huì)第十屆全國(guó)學(xué)術(shù)會(huì)議論文摘要集[C];2013年

9 李自成;李麗;嚴(yán)亨秀;呼海燕;張奇蘭;孫學(xué)川;鄭煜;;川芎嗪對(duì)缺氧所致大鼠呼吸效應(yīng)和腦干nNOS表達(dá)的影響[A];中國(guó)生理學(xué)會(huì)第五屆全國(guó)心血管、呼吸和腎臟生理學(xué)學(xué)術(shù)會(huì)議論文摘要匯編[C];2005年

10 關(guān)云謙;孫明;徐超;;腦缺血/再灌注時(shí)Calpain對(duì)nNOS表達(dá)的影響[A];中國(guó)藥理學(xué)會(huì)第十屆全國(guó)神經(jīng)學(xué)術(shù)會(huì)議暨浙江省藥理學(xué)會(huì)2002年年會(huì)論文摘要集[C];2002年

相關(guān)重要報(bào)紙文章 前1條

1 記者 張曄;焦慮癥體內(nèi)分子“開關(guān)”被找到[N];科技日?qǐng)?bào);2014年

相關(guān)博士學(xué)位論文 前6條

1 杜彩萍;神經(jīng)型一氧化氮合酶SUMO化在突觸可塑性中的作用[D];南京醫(yī)科大學(xué);2013年

2 周其岡;nNOS調(diào)控神經(jīng)元再生與抑郁癥[D];南京醫(yī)科大學(xué);2009年

3 張觀坡;谷氨酸興奮毒性在糖尿病大鼠選擇性nNOS神經(jīng)元減少及胃輕癱中的作用[D];第二軍醫(yī)大學(xué);2014年

4 李英慧;核因子（NF）-κB乙�；瘜�(duì)神經(jīng)型一氧化氮合酶（nNOS）基因表達(dá)的調(diào)控[D];中國(guó)醫(yī)科大學(xué);2007年

5 胡英華;基于nNOS表達(dá)的攢竹透睛明針刺治療弱視作用機(jī)制研究[D];長(zhǎng)春中醫(yī)藥大學(xué);2014年

6 朱新建;nNOS調(diào)控成年海馬齒狀回神經(jīng)元再生及其分子機(jī)制研究[D];南京醫(yī)科大學(xué);2006年

相關(guān)碩士學(xué)位論文 前10條

1 劉麗霞;α7nAChR和nNOS在Aβ誘導(dǎo)的認(rèn)知障礙大鼠中樞表達(dá)的變化及其對(duì)學(xué)習(xí)記憶功能的影響[D];山西醫(yī)科大學(xué);2015年

2 沈良華;不同張力擴(kuò)張子宮頸誘導(dǎo)大鼠延髓內(nèi)臟帶Fos及nNOS的表達(dá)變化[D];浙江大學(xué);2015年

3 饒?jiān)?Tat-LK15介導(dǎo)siRNA抑制nNOS表達(dá)治療神經(jīng)病理性疼痛的實(shí)驗(yàn)研究[D];南方醫(yī)科大學(xué);2015年

4 周恬恬;基于“Src-NR2-nNOS”信號(hào)通路的芍藥甘草配伍調(diào)控“GABA-Glu”平衡的神經(jīng)保護(hù)作用[D];北京中醫(yī)藥大學(xué);2016年

5 肖容容;nNOS通過改善線粒體功能參與缺血后適應(yīng)心肌保護(hù)作用[D];南京醫(yī)科大學(xué);2014年

6 宋奕辰;nNOS通過改善肌漿網(wǎng)功能參與心肌缺血后適應(yīng)保護(hù)作用[D];南京醫(yī)科大學(xué);2014年

7 張文tD;邊緣型人格障礙及其心理相關(guān)因素與nNOS、TPH1某因多態(tài)性的關(guān)聯(lián)研究[D];南京醫(yī)科大學(xué);2016年

8 曾娟;MrgC和腎上腺髓質(zhì)素受體對(duì)DRG中IL-1β、nNOS或pERK表達(dá)的作用研究[D];福建師范大學(xué);2016年

9 周露;nNOS參與缺血后適應(yīng)改善Ca~(2+)循環(huán)的心肌保護(hù)作用[D];南京醫(yī)科大學(xué);2015年

10 郝茂娟;心肌缺血后適應(yīng)通過nNOS/AMPK/mTOR通路增強(qiáng)自噬活性減輕缺血再灌注損傷[D];南京醫(yī)科大學(xué);2017年

，

本文編號(hào)：1847806