本文關(guān)鍵詞：中腦腹側(cè)被蓋區(qū)多巴胺能神經(jīng)元參與抑郁發(fā)生的機制研究　出處：《中國人民解放軍軍事醫(yī)學科學院》2016年碩士論文　論文類型：學位論文

  更多相關(guān)文章： 慢性疼痛 CUMS 抑郁癥 多巴胺能神經(jīng)元

【摘要】：抑郁癥(Depression)是一種慢性長期的精神類疾病,全球范圍內(nèi)約1.2億人口深受其害。雖然目前關(guān)于抑郁癥發(fā)生的病因和神經(jīng)生物學機制的研究已經(jīng)取得了突破性進展,但是關(guān)于抑郁癥發(fā)生的電生理和分子機制仍需要待進一步闡明。VTA多巴胺能神經(jīng)元在獎勵、動機、藥物成癮等動物行為中起重要作用。最近有文章報道,實驗證明中腦腹側(cè)被蓋區(qū)(Ventral tegmental area,VTA)多巴胺能神經(jīng)元可能參與了抑郁癥的發(fā)生。特異性激活或者抑制中腦腹側(cè)被蓋區(qū)多巴胺能神經(jīng)元的自發(fā)放電能明顯影響抑郁動物的行為學表現(xiàn),但其具體的分子機制還需要進一步的探究。慢性疼痛、慢性應激和抑郁癥的發(fā)生存在重要的聯(lián)系,臨床上許多慢性疼痛和長期遭受應激的患者常伴隨抑郁癥狀,但其機制確不清楚。研究目的:本研究擬模擬臨床上慢性疼痛和長期遭受應激的患者,建立慢性神經(jīng)痛和慢性溫和不可預知性刺激(CUMS)兩種抑郁大鼠模型;在此基礎上,運用在體多通道神經(jīng)電生理記錄系統(tǒng)(Multichannel Acquisition Processor(MAP)Neurophysiology System)記錄抑郁發(fā)生后的VTA多巴胺能神經(jīng)元自發(fā)電活動;并在藥物治療恢復后,記錄分析VTA多巴胺能神經(jīng)元的電活動的變化情況;并應用免疫組化的方法,分析在此病理過程中超極化激活的環(huán)核苷酸門控的離子通道(HCN)通道表達改變的情況,從而初步探討VTA多巴胺能神經(jīng)元參與抑郁癥發(fā)生的電生理分子機制。研究方法:1.抑郁大鼠模型的建立:(1)慢性神經(jīng)痛誘發(fā)抑郁癥:我們采用坐骨神經(jīng)分支選擇性損傷模型(spared nerve injury,SNI),采用機械性刺激縮足閾值、糖水偏好、強迫游泳以及曠場實驗作為行為學評定指標。實驗開始前,48只SPF成年健康大鼠在隔離屏障環(huán)境適應一周后,進行隨機分組,分為假手術(shù)組大鼠12只和SNI組大鼠36只,并測得機械痛閾值基值。只暴露假手術(shù)組大鼠神經(jīng)而不進行結(jié)扎,結(jié)扎并剪斷SNI組大鼠的腓總神經(jīng)和脛神經(jīng),并且需要完整保留,不能牽拉腓腸神經(jīng)。在SNI手術(shù)后的第3、14、28、56天,進行機械性刺激縮足閾值測得,第14、28、56天進行礦場實驗、糖水偏好、強迫游泳實驗進行抑郁行為學評定。將SNI組大鼠隨機分為兩組,分別腹腔注射一種臨床上廣泛使用的神經(jīng)病理性疼痛鎮(zhèn)痛藥加巴噴丁(100 mg/kg)和生理鹽水14天,進行行為學觀察。(2)建立另一種大鼠抑郁癥模型:即采用慢性不可預知輕度應激(chronic unpredictable mild stress,CUMS)刺激的方法對大鼠進行長期應激壓力刺激造模。采用百分比糖水偏好、曠場下活動距離以及體重變化作為抑郁發(fā)生與否的行為學評定指標。實驗前,大鼠在實驗動物中心屏障隔離環(huán)境飼養(yǎng)一周,使其適應CUMS刺激環(huán)境。并按照隨機分組的原則將實驗動物隨機分為對照組和CUMS組。然后進行CUMS造模,在造模過程中,對照組大鼠3-4只合籠正常飼養(yǎng),實驗組大鼠單籠飼養(yǎng)并進行CUMS造模6-8周,隨后根據(jù)行為學結(jié)果,經(jīng)統(tǒng)計分析后得到具有抑郁行為大鼠。把經(jīng)CUMS刺激后具有抑郁表型的大鼠進行氟西汀治療恢復抑郁表型:其中一部分大鼠腹腔注射21天生理鹽水,另一部分大鼠連續(xù)腹腔注射21天的氟西汀,并給藥結(jié)束后,進行行為學評價,得到抑郁恢復的大鼠以及抑郁大鼠,所有實驗動物均需要進行行為學評價。2.多通道電生理技術(shù)記錄分析:我們采用Plexon公司的多通道神經(jīng)電生理記錄分析系統(tǒng)對實驗動物進行在體電生理記錄,并分析中腦腹側(cè)被蓋區(qū)VTA多巴胺能神經(jīng)元的自發(fā)放電特征。在CUMS造模后篩選抑郁癥狀大鼠,隨后進行氟西汀注射進行治療,記錄分析氟西汀治療后大鼠、抑郁癥大鼠、以及對照組大鼠的中腦腹側(cè)被蓋區(qū)多巴胺能神經(jīng)元自發(fā)電活動,分析自發(fā)放電頻率與爆發(fā)式放電活動。在慢性神經(jīng)痛誘發(fā)抑郁癥實驗中,通過篩選出慢性神經(jīng)痛誘導的抑郁癥狀的大鼠進行加巴噴丁注射,記錄分析加巴噴丁治療組大鼠、神經(jīng)損傷組大鼠,以及假手術(shù)組大鼠的VTA多巴胺能神經(jīng)元自發(fā)放電特征。3.大鼠中腦腹側(cè)被蓋區(qū)免疫熒光分析:在慢性神經(jīng)痛誘發(fā)抑郁癥大鼠的VTA腦區(qū),免疫熒光雙標記酪氨酸羥化酶(Tyrosine hydroxylase,TH)與超極化激活的環(huán)核苷酸離子通道(Hyperpolarization-activated cyclic nucleotide-gated channel,HCN)蛋白,觀察并統(tǒng)計分析HCN通道蛋白在中腦腹側(cè)被蓋區(qū)多巴胺能神經(jīng)元上的表達變化。研究結(jié)果:1.在慢性神經(jīng)痛誘發(fā)抑郁癥實驗中,相對比與假手術(shù)組大鼠,我們發(fā)現(xiàn)SNI大鼠的機械刺激縮足閾值下降,表現(xiàn)為明顯的統(tǒng)計學差異(n=6,P0.01),糖水偏好(n=6,P0.01),曠場行走總路程(n=8,P0.01)均有所下降,強迫游泳靜止時間增加(n=10,P0.01)。在經(jīng)過14天加巴噴丁治療后,SNI組大鼠的抑郁行為得到緩解,相比較于SNI注射生理鹽水組的大鼠,加巴噴丁注射組大鼠的機械性刺激縮足反射閾值增加,(n=10,P0.001),在曠場下活動的總路程增加(n=6,P0.001),具有明顯的統(tǒng)計學意義。在強迫游泳中的靜止時間減少(n=8,P0.01),在糖水偏好方面增加(n=8,P0.01),表現(xiàn)為明顯的統(tǒng)計學差異。SNI組大鼠VTA多巴胺能神經(jīng)元自發(fā)放電頻率較假手術(shù)組大鼠增加,出現(xiàn)明顯的統(tǒng)計學差異(P0.001),簇狀放電活動顯著增加(P0.001);經(jīng)過加巴噴丁治療后,加巴噴丁治療組大鼠VTA多巴胺能神經(jīng)元自發(fā)放電頻率較SNI組大鼠有所降低,存在統(tǒng)計學差異(P0.05),但簇狀放電活動顯著增加,表現(xiàn)出明顯的統(tǒng)計學差異(P0.01);但相比較于Sham組大鼠,加巴噴丁治療組大鼠的VTA多巴胺能神經(jīng)元自發(fā)放電頻率仍然增加(P0.01),簇狀放電活動出現(xiàn)高度統(tǒng)計學差異(P0.001,n=132(SNI+Saline),n=81(SNI+GBP),n=71(Sham))。同時HCN1蛋白在加巴噴丁治療組大鼠與鹽水注射組大鼠和Sham組大鼠的VTA腦區(qū)表達沒有差異(P0.05);相比較于Sham組大鼠,HCN2在加巴噴丁治療組大鼠(P0.05)以及鹽水組大鼠中均高調(diào)(P0.01),但是二者之間沒有差異(P0.05),我們沒有發(fā)現(xiàn)HCN3在VTA的表達,同時沒有找到HCN4和TH在VTA共表達的細胞。2.在CUMS抑郁癥模型實驗中,在第一次8周CUMS造模后,與對照組大鼠相比較,CUMS造模組大鼠的糖水偏好比率下降,出現(xiàn)高度統(tǒng)計學差異(n=12,P0.001),體重增長緩慢,出現(xiàn)統(tǒng)計學差異(n=12,P0.05),曠場下的活動總路程沒有差異(n=12,P0.05),經(jīng)過21天的氟西汀治療后,氟西汀注射組大鼠的糖水偏好比率較鹽水注射組大鼠增加,表現(xiàn)為明顯統(tǒng)計學差異(n=12,P0.01),而體重變化與曠場活動總路程沒有變化(n=12,P0.05)。CUMS大鼠VTA多巴胺能神經(jīng)元自發(fā)放電頻率較對照組大鼠明顯增加,有顯著的統(tǒng)計學差異(P0.01),簇狀放電增加,表現(xiàn)為高度的統(tǒng)計學差異(P0.001);經(jīng)過21天氟西汀治療后,氟西汀治療組大鼠的VTA多巴胺能神經(jīng)元自發(fā)放電頻率較CUMS組大鼠降低,但是沒有統(tǒng)計學差異(P0.05),但較對照組大鼠表現(xiàn)出統(tǒng)計學差異(P0.05)。氟西汀治療組大鼠VTA多巴胺能神經(jīng)元簇狀放電活動中動作電位的數(shù)量相比較CUMS降低,表現(xiàn)出統(tǒng)計學差異;較對照組大鼠仍然增加,表現(xiàn)為統(tǒng)計學差異(P0.05);而簇狀放電的持續(xù)時間同CUMS組大鼠比較沒有差異,同對照組大鼠比較表現(xiàn)為高度的統(tǒng)計學差異(P0.001)(n=61(control);n=58(CUMS);n=83(CUMS+fluoxetine))。研究結(jié)論:1.在慢性疼痛和慢性應激(CUMS)誘發(fā)的兩種抑郁癥模型大鼠中,中腦腹側(cè)被蓋區(qū)(VTA)多巴胺能神經(jīng)元電信號都發(fā)生改變。該研究提示,慢性應激(疼痛或者刺激)導致的VTA腦區(qū)多巴胺能神經(jīng)元興奮性改變,與抑郁癥的發(fā)生具有很強的相關(guān)性。2.慢性疼痛誘發(fā)抑郁癥狀的模型大鼠中,超極化激活的環(huán)核苷酸離子通道蛋白(HCN)的表達高調(diào)。由于HCN在神經(jīng)元的興奮性調(diào)節(jié)中發(fā)揮重要的作用,本研究提示,長期的疼痛刺激誘發(fā)的抑郁癥,可能與VTA多巴胺能神經(jīng)元HCN表達高調(diào),從而引發(fā)的神經(jīng)元興奮性改變相關(guān)。
[Abstract]:Depression (Depression) is a chronic mental illness, approximately 120 million of the population worldwide suffer. Although the current research on the etiology of depression and neurobiological mechanisms has made breakthrough progress, but about the depression and the electrophysiological and molecular mechanisms still need to be elucidated.VTA dopaminergic neurons in reward that motivation plays an important role in drug addiction and other animal behavior. The article reported recently, experiments show that the ventral tegmental area (Ventral tegmental, area, VTA) dopaminergic neurons may be involved in the occurrence of depression. The specificity of activation or inhibition of midbrain VTA dopamine neurons from firing could significantly affect the animal depression the behavioral performance, but its molecular mechanism needs further study. Chronic pain, chronic stress and depression There is an important relationship, many clinical chronic pain and long suffering stress patients often associated with depressive symptoms, but the mechanism is not clear. Objective: This study intends to simulate clinical chronic pain and long suffering stress in patients with established chronic neuropathic pain and chronic unpredictable mild stimulation (CUMS) two models rats with depression; on this basis, using the in vivo multi-channel electrophysiological recording system (Multichannel Acquisition Processor (MAP) Neurophysiology System) recorded depression VTA dopaminergic neurons spontaneous electrical activity; and in the drug treatment after recovery, changes in recording electrical activity analysis of VTA dopaminergic neurons; and immunohistochemical analysis of ion channels, this pathological process of hyperpolarization activated cyclic nucleotide gated (HCN) channel expression changes, and from the preliminary study of VTA DOPA Dopaminergic neuronal electrophysiological mechanisms involved in depression. Methods: a rat model of depression: 1. (1) chronic neuropathic pain induced depression: we use the spared nerve injury model (spared nerve injury, SNI), the mechanical withdrawal threshold, sucrose preference, forced swimming and open field the experiment for the behavioral assessment indicators. Before the start of the experiment, 48 SPF adult rats adapted for one week in the isolation barrier environment, were randomly divided into sham operation group, 12 rats in group SNI and 36 rats, and measured the mechanical pain threshold base value. Only exposed rats in sham operation group without nerve ligation, ligation of the common peroneal nerve and tibial nerve cut SNI rats, and the need to retain the integrity, not to pull the sural nerve. After SNI surgery at 3,14,28,56 days, were measured the mechanical withdrawal threshold of the 14,28,56 day For field test, sucrose preference, forced swimming test for depression behavior evaluation. Rats in group SNI were randomly divided into two groups, neuropathic pain and analgesic gabapentin were injected a clinically widely used (100 mg/kg) and saline for 14 days, behavioral observation. (2) the establishment of another a rat model of depression: the chronic unpredictable mild stress (chronic unpredictable mild stress, CUMS) stimulation method for long-term stress on rat model. The percentage of stimulation of sucrose preference, open field activity distance and weight change as the Depression Behavior and whether or not the evaluation index. Before the experiment, rats in the experimental animal center of environmental barrier isolation feed for a week, make it adapt to the stimulation of CUMS environment. And in accordance with the principles of randomized experimental animal were randomly divided into control group and CUMS group. Then in the CUMS model, the In the process of modeling, the rats in the control group 3-4 only mated with normal feeding, experimental rats reared in single cage and CUMS model for 6-8 weeks, then according to the results of behavior, after statistical analysis with depressive behavior of rats after CUMS stimulation. The phenotype of rats with depression recovery of fluoxetine in the treatment of depression phenotype: some of the rats by intraperitoneal injection of normal saline for 21 days, another part of the rats by intraperitoneal injection for 21 days and fluoxetine, after medication, behavioral assessment, get recovery from depression rats and rats with depression, all experimental animal are required to the evaluation of behavior of.2. multi channel electrophysiology Technology of recording and analysis: we use multi channel neural Plexon, electrophysiological recording and analysis system of experimental animal in vivo electrophysiological recording, and analyze the characteristics of spontaneous discharges of VTA dopaminergic neurons in the VTA in CUMS. After modeling the screening of depressive symptoms in rats, followed by injection of fluoxetine treatment, recording and analysis of fluoxetine in the treatment of rats after depression rats and control group rats midbrain VTA dopaminergic neurons and spontaneous activity, analysis of spontaneous discharge frequency and the bursting activity. In chronic neuropathic pain induced depression in the experiment for injection by screening out, gabapentin chronic neuropathic pain induced depression rats, recording and analysis of gabapentin in the treatment group rats, nerve injury rats, and the rats in the sham operation group VTA spontaneous discharge characteristics of.3. dopaminergic neurons in ventral tegmental area: immunofluorescence analysis in VTA brain regions of chronic nerve the pain induced depression rats, immunofluorescence double labeling of tyrosine hydroxylase (Tyrosine hydroxylase, TH) and hyperpolarization activated cyclic nucleotide ion channels (Hyperpolarization-act Ivated cyclic nucleotide-gated channel, HCN) protein, observation and statistical analysis of HCN channel protein in VTA dopaminergic neurons. Expression of the results: 1. in chronic neuropathic pain induced depression in the experiment, compared with the sham operation group rats, we found that SNI rats mechanical withdrawal threshold decline, showed statistically significant difference (n=6, P0.01), sugar preference (n=6, P0.01), open field walking distance (n=8, P0.01) were decreased, forced swimming immobility time increased (n=10, P0.01). After 14 days of gabapentin treatment, the depressive behaviors of rats in group SNI were alleviated SNI, compared with the injection of saline group rats, rats injected with gabapentin mechanical stimulus withdrawal threshold increased (n=10, P0.001), the total distance in open field under the increase of (n=6, P0.001), which was statistically significant in the forced. A reduction in the swimming time (n=8, P0.01), the increase in sucrose preference on (n=8, P0.01, VTA) showed significant difference in the.SNI group rats dopamine neurons firing frequency than those in the sham operation group rats increased, there was significant differences (P0.001), cluster discharge activity increased significantly (P0.001); after gabapentin treatment, gabapentin treated rats VTA dopaminergic neurons firing frequency than the SNI rats decreased, there was significant difference (P0.05), but the cluster activity increased significantly, showing a statistically significant difference (P0.01); but compared to Sham rats the rats in the treatment group, gabapentin VTA dopaminergic neurons spontaneous discharge frequency (P0.01), there was still increased highly significant difference of cluster activity (P0.001, n=132 (SNI+Saline), n =81 (SNI+GBP), n=71 (Sham)). At the same time, HCN1 protein in gabah Gabapentin treated rats and saline injected group rats and Sham group rats VTA expression did not differ between brain regions (P0.05); compared with Sham rats, HCN2 rats in the treatment group of gabapentin (P0.05) and saline group rats were high (P0.01), but no difference between the two (P0.05), we found no HCN3 expression in VTA, but did not find the co expression of HCN4 and TH in VTA.2. cells in CUMS depression model experiment, in the first 8 weeks after CUMS, compared with the control group of rats, decreased sucrose preference ratio of CUMS model rats, appears highly statistically the difference (n=12, P0.001), a slow increase of body weight, there was significant difference (n=12, P0.05), no difference in open field under the total distance (n=12, P0.05), fluoxetine after 21 days of treatment, the sucrose preference ratio of fluoxetine in rats injected with saline injection group rats showed significant increase. No statistical difference (n=12, P0.01), and the changes of body weight and open field activity did not change the total distance (n=12, P0.05).CUMS VTA rat dopaminergic neurons firing frequency of rats significantly increased compared with the control group, there was a statistically significant difference (P0.01), cluster discharge is increased, the height difference the (P0.001); after 21 days after fluoxetine treatment, fluoxetine treatment group rats VTA dopamine neurons firing frequency than the CUMS rats decreased, but no significant difference (P0.05), but compared with the control group rats showed significant difference (P0.05). Fluoxetine in the treatment of VTA rats dopaminergic the number of clusters of neurons in action potential discharge activity compared to CUMS decreased, showing statistical differences; compared with the control group rats still showed statistically significant increase (P0.05); while the duration of burst discharge with the rats in the CUMS group compared with the no difference. According to comparison of performance group rats were statistically significant differences between the height (P0.001) (n=61 (control); n=58 (CUMS); n=83 (CUMS+fluoxetine)). Conclusions: 1. in chronic pain and chronic stress (CUMS) of two kinds of rat model of depression induced in the ventral tegmental area dopamine (VTA) these electric signals are changed. The research suggests that chronic stress (or pain stimulation) in VTA brain dopaminergic neuronal excitability changes in rat model has a strong correlation between.2. and chronic pain induced depression and depression in the camp hyperpolarization activated ion channel protein (HCN) expression high profile. Because HCN play an important role in regulating the excitability of neurons in this study suggest that chronic pain induced by depression, VTA and HCN high expression of dopaminergic neurons, causing changes in neuronal excitability Relevant.

【學位授予單位】：中國人民解放軍軍事醫(yī)學科學院
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R749.4

【相似文獻】

相關(guān)期刊論文 前10條

1 盛文利,朱良付,曾進勝,黃如訓;雜種多巴胺能神經(jīng)元細胞系的體外分化和形態(tài)學特征[J];中國神經(jīng)精神疾病雜志;2004年01期

2 陳梅玲;沈岳飛;;影響多巴胺能神經(jīng)元體內(nèi)外分化的因素[J];基礎醫(yī)學與臨床;2008年04期

3 范東艷;王蘋;劉然;牛鳳蘭;杜波;;小膠質(zhì)細胞活化刺激骨髓間充質(zhì)干細胞釋放膠質(zhì)細胞源性神經(jīng)營養(yǎng)因子保護多巴胺能神經(jīng)元的實驗[J];中國組織工程研究與臨床康復;2010年06期

4 夏立平;李凌云;費喜峰;梁中琴;;自噬參與6-羥基多巴胺誘導多巴胺能神經(jīng)元死亡的實驗觀察[J];南方醫(yī)科大學學報;2010年12期

5 王大力;趙鵬;劉強;王彥;趙輝;彭延波;杜利清;;脂多糖誘導小膠質(zhì)細胞活化對多巴胺能神經(jīng)元的損傷作用[J];中華臨床醫(yī)師雜志(電子版);2012年08期

6 牛平,呂永利,王耀山,何祥;堿性成纖維細胞生長因子對體外培養(yǎng)多巴胺能神經(jīng)元營養(yǎng)作用[J];中國醫(yī)科大學學報;2001年06期

7 張文華,王曉民,楊揚,薛冰,崔振中,吳承遠,韓濟生;人膠質(zhì)細胞源性神經(jīng)營養(yǎng)因子基因工程細胞保護多巴胺能神經(jīng)元的實驗研究[J];中華醫(yī)學雜志;2001年22期

8 李慶國,林志國,劉恩重,戴欽舜;神經(jīng)干細胞向多巴胺能神經(jīng)元分化的條件[J];中華神經(jīng)外科雜志;2002年02期

9 姜曉兵,趙洪洋,周鳳,劉如恩,周偉,張建國;穩(wěn)定表達GDNF/EGFP融合基因的骨髓基質(zhì)干細胞對多巴胺能神經(jīng)元的保護作用[J];中國神經(jīng)科學雜志;2004年05期

10 胡琦;康慧聰;劉曉艷;許峰;朱遂強;;骨髓間充質(zhì)干細胞體外分化為多巴胺能神經(jīng)元的實驗研究[J];神經(jīng)損傷與功能重建;2006年04期

相關(guān)會議論文 前10條

1 張艷新;李軍泉;徐群淵;;炎癥因素與黑質(zhì)多巴胺能神經(jīng)元選擇性變性相關(guān)性研究[A];Proceedings of the 8th Biennial Conference of the Chinese Society for Neuroscience[C];2009年

2 劉彬;謝俊霞;;雌激素及白鳳丸對中樞多巴胺能神經(jīng)元的調(diào)節(jié)和保護作用[A];中國生理學會張錫鈞基金會第八屆全國青年優(yōu)秀生理學學術(shù)論文綜合摘要[C];2003年

3 汪錫金;葉民;張宇紅;陳生弟;;白細胞介素-10抑制促炎因子生成保護多巴胺能神經(jīng)元[A];第十一屆全國神經(jīng)病學學術(shù)會議論文匯編[C];2008年

4 周愛霞;楊慧;;野生型α-synuclein過表達對大鼠多巴胺能神經(jīng)元的影響[A];中國神經(jīng)科學學會第六屆學術(shù)會議暨學會成立十周年慶祝大會論文摘要匯編[C];2005年

5 鄭超;汪萌芽;Jie WU;;κ-阿片受體對大鼠腹側(cè)被蓋區(qū)多巴胺能神經(jīng)元自發(fā)放電的差異性調(diào)節(jié)作用[A];Proceedings of the 8th Biennial Conference of the Chinese Society for Neuroscience[C];2009年

6 董曉莉;謝俊霞;;雌激素和類雌激素對杏仁核多巴胺能神經(jīng)元功能的影響[A];中國生理學會第21屆全國代表大會暨學術(shù)會議論文摘要匯編[C];2002年

7 張振濤;曹學兵;孫圣剛;王嵐;喬嫻;劉紅進;;蛋白酶體抑制劑誘導多巴胺能神經(jīng)元重啟細胞周期的作用及機制[A];第九次全國神經(jīng)病學學術(shù)大會論文匯編[C];2006年

8 李寶園;豐玲;王雁春;郭敏芳;馬存根;;睪丸支持細胞誘導大鼠神經(jīng)干細胞向多巴胺能神經(jīng)元分化作用研究[A];2008年神經(jīng)內(nèi)分泌暨神經(jīng)免疫內(nèi)分泌學術(shù)研討會論文摘要匯編[C];2008年

9 王國權(quán);趙忠新;趙瑛;;褪黑素對多巴胺能神經(jīng)元的保護作用[A];中華醫(yī)學會第七次全國神經(jīng)病學學術(shù)會議論文匯編[C];2004年

10 胡琦;康慧聰;劉小艷;許峰;朱隧強;;骨髓間充質(zhì)干細胞分化為多巴胺能神經(jīng)元的實驗研究[A];第九次全國神經(jīng)病學學術(shù)大會論文匯編[C];2006年

相關(guān)重要報紙文章 前1條

1 張中橋;培補肝腎藥可保護多巴胺能神經(jīng)元[N];中國醫(yī)藥報;2005年

相關(guān)博士學位論文 前10條

1 方偉;多巴胺能神經(jīng)元軸突變性在MPTP誘導的帕金森病模型中的作用研究[D];第四軍醫(yī)大學;2015年

2 王馥麗;神經(jīng)毒素特異損傷的多巴胺能神經(jīng)元與免疫細胞相互作用研究[D];北京理工大學;2015年

3 陳銳;DDIT4在甲基苯丙胺介導的神經(jīng)毒性及心臟毒性中的作用[D];南方醫(yī)科大學;2016年

4 王晶;人類胚胎干細胞誘導分化為多巴胺能神經(jīng)元的實驗研究[D];中國人民解放軍軍醫(yī)進修學院;2008年

5 趙鵬;外源多巴胺對α-Synuclein過表達多巴胺能神經(jīng)元的影響[D];天津醫(yī)科大學;2009年

6 盛超;小鼠體細胞向多能性神經(jīng)前體細胞和成熟多巴胺能神經(jīng)元的直接轉(zhuǎn)分化[D];東北農(nóng)業(yè)大學;2012年

7 姚謙明;鼠骨髓源神經(jīng)干細胞向多巴胺能神經(jīng)元定向誘導分化[D];第一軍醫(yī)大學;2006年

8 何秀全;羅格列酮通過抑制小膠質(zhì)細胞活化而保護多巴胺能神經(jīng)元的研究[D];山東大學;2012年

9 鐘善傳;α-SYN和EN1在小鼠的發(fā)育學表達及其在PD模型中作用的實驗研究[D];第三軍醫(yī)大學;2010年

10 賈曉晶;帕金森氏病體外細胞模型的建立及胞二磷膽堿對多巴胺能神經(jīng)元保護作用的研究[D];吉林大學;2004年

相關(guān)碩士學位論文 前10條

1 付波;中腦腹側(cè)被蓋區(qū)多巴胺能神經(jīng)元參與抑郁發(fā)生的機制研究[D];中國人民解放軍軍事醫(yī)學科學院;2016年

2 呂立;順序性化學誘導促大鼠骨髓間充質(zhì)干細胞向多巴胺能神經(jīng)元分化治療帕金森的實驗研究[D];南京醫(yī)科大學;2010年

3 高健;神經(jīng)膠質(zhì)源性神經(jīng)營養(yǎng)因子和白細胞介素-1α促進大鼠骨髓基質(zhì)細胞誘導分化為多巴胺能神經(jīng)元的實驗研究[D];第一軍醫(yī)大學;2006年

4 徐曉帆;黃芩莖葉總黃酮對多巴胺能神經(jīng)元的保護作用[D];泰山醫(yī)學院;2014年

5 劉晶;榆紫葉甲Ambrostoma quadriim-pressum腦內(nèi)多巴胺能神經(jīng)元的免疫組織化學定位研究[D];東北師范大學;2010年

6 范瑞芳;骨髓間充質(zhì)干細胞體外定向分化為多巴胺能神經(jīng)元的實驗研究[D];廣西醫(yī)科大學;2009年

7 李海波;過表達野生型及帕金森病相關(guān)突變型α-synuclein對人胚胎干細胞向多巴胺能神經(jīng)元分化的影響[D];中南大學;2010年

8 羅彥妮;外源性血管緊張素Ⅱ誘導神經(jīng)干細胞向多巴胺能神經(jīng)元分化的實驗研究[D];廣西醫(yī)科大學;2009年

9 葉杰明;沉默信息調(diào)節(jié)因子1在脂多糖激活小膠質(zhì)細胞介導多巴胺能神經(jīng)元毒性損傷中的保護作用[D];南方醫(yī)科大學;2013年

10 李燕皎;胚胎干細胞定向誘導的多巴胺能神經(jīng)元及其對食蟹猴的移植研究[D];云南大學;2015年

，

本文編號：1415551