本文選題：精神分裂癥 + gamma震蕩��； 參考：《昆明醫(yī)科大學》2017年碩士論文

【摘要】：[背景與目的]精神分裂癥被認為是一種神經(jīng)系統(tǒng)結(jié)構(gòu)功能發(fā)育異常及變性所致疾病,常以思想和行為不協(xié)調(diào)、妄想、幻覺等陽性癥狀及主動性降低、社會功能減退、情感淡漠等陰性癥狀為表現(xiàn)。其中認知功能障礙是精神分裂癥的核心缺損癥狀。許多實驗表明,谷氨酸能(Glutamate,Glu)與多巴胺能(dopamine, DA)神經(jīng)遞質(zhì)功能紊亂造成神經(jīng)網(wǎng)絡(luò)興奮-抑制失平衡,導(dǎo)致了精神分裂癥陽性癥狀與陰性癥狀并存的結(jié)果。這兩類神經(jīng)元能夠通過γ-氨基丁酸(γ-aminobutyric acid,GABA)能中間神經(jīng)元相互作用相互影響。GABA能中間神經(jīng)元從結(jié)構(gòu)、生理功能及分子特性上分為許多種亞型,其中小清蛋白(Parvalbumin, PV)陽性的GABA能中間神經(jīng)元的異常放電引起gamma震蕩異常,導(dǎo)致認知功能受損。gamma震蕩在神經(jīng)生理功能中扮演著重要角色,比如選擇注意力、各種感覺的加工、感知覺特性的整合以及工作記憶的儲存與取回等,而這些功能的損害恰好是精神分裂癥的核心癥狀。與健康人群相比,異常的前額葉gamma震蕩常常可以在精神分裂癥患者身上檢測出來。目前認為,前額葉gamma震蕩異常雖不是精神分裂癥的特有現(xiàn)象,但其對于該疾病的診斷、治療以及預(yù)后評估均有重要意義。許多實驗證實了應(yīng)用N-甲基-D-天冬氨酸鹽(N-methyl-D-aspartate, NMDA)受體拮抗劑或DA受體激動劑/拮抗劑后能使前額葉gamma震蕩能量異常,但結(jié)論并不一致。苯環(huán)己哌啶(Phencyclidine,PCP)是一種非特異性NMDA受體拮抗劑,能夠較好的模擬精神分裂癥樣癥狀。目前研究特定狀態(tài)下非人靈長類前額葉gamma震蕩的實驗較少。我們以慢性PCP食蟹猴作為主要研究對象,進一步驗證DA能及Glu能神經(jīng)遞質(zhì)對前額葉gamma震蕩的影響。[方法]實驗對象為隨機挑選的4只正常成年雌性石蟹猴、6只長期注射PCP的成年雌性食蟹猴作為實驗組。采用頭皮植入電極記錄裝置,電極分別置于雙側(cè)前額部(F3、F4),地線接雙側(cè)眉弓中心(D),參考線接單側(cè)耳垂(A),給予條件測量范式(Conditioning-testing paradigm)的雙聲刺激(雙聲間隔時間為500ms,每對雙聲刺激之間間隔為5-10s的重復(fù)性雙聲刺激模式,聲音強度為75 dB,背景噪音:45dB)誘發(fā)腦電活動來檢測。首先對比正常對照組食蟹猴與慢性PCP實驗組未注藥雙側(cè)前額葉基線gamma震蕩功率是否有差異。再分別給予3種不同劑量的DA受體激動劑溴隱亭(0.313 mg/kg,0.625 mg/kg,1.25 mg/kg)及3種不同劑量DA受體拮抗劑氟哌啶醇(0.001 mg/kg,0.01 mg/kg,0.05 mg/kg)后,分時段記錄腦電信號(0-30min、30-60min),離線提取、計算食蟹猴雙側(cè)前額葉gamma震蕩功率,并進行統(tǒng)計學分析。[結(jié)果]1.實驗一(正常對照組與慢性PCP組的基線比較);慢性PCP組食蟹猴雙側(cè)前額葉基線gamma震蕩功率值較正常對照組顯著下降。2.實驗二(溴隱亭組,Bromocriptine):低劑量溴隱亭(0.312mg/kg)使慢性PCP食蟹猴左側(cè)前額葉gamma震蕩功率先顯著升高再顯著降低;使右側(cè)前額葉gamma震蕩功率在注藥后30-60min內(nèi)較注藥后0-30min明顯下降。中等劑量組溴隱亭(0. 625mg/kg)對慢性PCP食蟹猴雙側(cè)前額葉gamma震蕩功率無顯著影響。高劑量組溴隱亭(1. 25mg/kg)對慢性PCP食蟹猴雙側(cè)前額葉gamma震蕩功率無顯著影響。3.實驗三(氟哌啶醇組,Haloperidol):低劑量氟哌啶醇(0.001mg/kg)對慢性PCP食蟹猴雙側(cè)前額葉gamma震蕩功率未造成顯著影響。中等劑量氟哌啶醇(0. 01mg/kg)對慢性PCP食蟹猴雙側(cè)前額葉gamma震蕩功率未造成顯著影響。高劑量氟哌啶醇(0.05mg/kg)使慢性PCP食蟹猴較未注藥時左側(cè)前額葉gamma震蕩功率顯著升高;右側(cè)前額葉在注藥后0-30min內(nèi)gamma功率較未注藥時顯著升高。[結(jié)論]長期應(yīng)用NMDA受體拮抗劑PCP能誘導(dǎo)食蟹猴雙側(cè)前額葉gamma震蕩能量下降。低劑量DA受體激動劑溴隱亭能使慢性PCP食蟹猴雙側(cè)前額葉gamma震蕩功率呈先升高再降低的趨勢,可能與該藥物在不同時間段主要作用的部位不同引起。高劑量DA受體拮抗劑氟哌啶醇能增加慢性PCP食蟹猴模型雙側(cè)前額葉gamma震蕩功率,可能改善精神分裂癥患者認知相關(guān)癥狀。表明DA系統(tǒng)功能紊亂對精神分裂癥的認知障礙起著一定的作用,并且DA、Glu及GABA三者平衡失調(diào)構(gòu)成了精神分裂癥的病理生理基礎(chǔ)。
[Abstract]:[background and purpose] schizophrenia is considered to be a disease caused by dysfunctional dysplasia and degeneration of the nervous system. It often shows negative symptoms such as disharmony of thought and behavior, delusions, hallucinations and other positive symptoms, social dysfunction, indifference and other negative symptoms. Cognitive dysfunction is the core defect of schizophrenia. Symptoms. Many experiments show that Glutamate (Glu) and dopamine (dopamine, DA) neurotransmitter dysfunction cause nerve network excitation - inhibition of imbalance, which results in the coexistence of both positive and negative symptoms of schizophrenia. These two types of neurons can be able to use gamma aminobutyric acid (gamma -aminobutyric acid, GABA) to be in the middle God. The interaction of.GABA can be divided into many subtypes from the structure, physiological function and molecular characteristics, in which the abnormal discharge of the Parvalbumin, PV positive GABA intermediate neurons causes the gamma oscillation to be abnormal, causing the cognitive impairment to play an important role in the neurophysiological function. Color, such as the choice of attention, the processing of various sensations, the integration of sensory perception and the storage and retrieval of working memory, and the impairment of these functions is the core symptom of schizophrenia. Compared with the healthy population, abnormal prefrontal gamma concussion can often be detected in the patients with seminal schizophrenia. Although abnormal gamma turbulence in the frontal lobe is not a characteristic of schizophrenia, it is of great significance for the diagnosis, treatment and prognosis of the disease. Many experiments have proved that the application of N- methyl -D- aspartate (N-methyl-D-aspartate, NMDA) receptor antagonist or DA receptor agonist / antagonist can make the gamma concussion energy in the prefrontal lobe Abnormal, but the conclusion is not consistent. Phencyclidine (PCP) is a nonspecific NMDA receptor antagonist, which can better simulate schizophrenia like symptoms. At present, there are few experiments on the gamma concussion of non human primate prefrontal lobes under specific state. We use chronic PCP food cynomolgus as the main research object, and further verify DA The effects of Glu neurotransmitters on the gamma concussion of prefrontal lobes. [Methods] 4 normal adult female cynomolgus monkeys were selected randomly, and 6 adult female cynomolgus monkeys with long-term injection of PCP were used as the experimental group. The electrodes were implanted into the electrode recording device of the scalp implantation, the electrodes were placed in the anterior frontal part (F3, F4), and the ground wire was connected to the bilateral eyebrow bow Center (D). One side lobe of the ear lobe (A) was followed by a double acoustic stimulation of the conditional measurement paradigm (Conditioning-testing paradigm) (a double sound interval of 500ms, a double sound stimulation mode of 5-10S between each pair of stimuli, the sound intensity of 75 dB, the background noise: 45dB) induced electroencephalogram detection. First, compared with the normal control group, the cynomolgus monkeys were compared with the normal control group. 3 different doses of DA receptor agonist bromocriptine (0.313 mg/kg, 0.625 mg/kg, 1.25 mg/kg) and 3 different doses of DA receptor antagonist haloperidol (0.001 mg/kg, 0.01 mg/kg, 0.05 mg/kg) were given separately, and the EEG signals were recorded at a period of time (0-30min). (0-30min), the EEG signals were recorded in the chronic PCP test group. 30-60min), off-line extraction, calculation of gamma shock power of bilateral prefrontal lobes in cynomolgus, and statistical analysis. [results]1. Experiment 1 (comparison between normal control group and baseline of chronic PCP group); the value of gamma shock power of bilateral prefrontal baseline in chronic PCP group was significantly lower than that in normal group,.2. experiment two (bromocriptine group, Bromocriptine): The low dose of bromocriptine (0.312mg/kg) significantly increased the gamma shock power of the left prefrontal lobe of chronic PCP cynomolgus and then decreased significantly, and the gamma concussion power of the right prefrontal lobe decreased significantly in 30-60min after injection than after injection of the drug. The moderate dose group of bromocriptine (0. 625mg/kg) did not have the power of gamma concussion in the bilateral prefrontal cortex of chronic PCP cynomolgus monkey Significant effect. The high dose group of bromocriptine (1. 25mg/kg) had no significant effect on the gamma concussion power of the bilateral prefrontal cortex of chronic PCP cynomolgus,.3. experiment three (haloperidol group, Haloperidol): low dose haloperidol (0.001mg/kg) had no significant effect on the gamma concussion power of bilateral prefrontal cortex of chronic PCP cynomolgus macaque. Middle dose haloperidol (0. 01mg/kg). There was no significant effect on the gamma concussion power of the bilateral prefrontal cortex of chronic PCP cynomolgus. High dose of haloperidol (0.05mg/kg) increased the gamma shock power of the left prefrontal lobe of the chronic PCP cynomolgus, while the right prefrontal lobe was significantly higher in the gamma power in 0-30min after the injection. [Conclusion] the long-term application of NMDA receptor antagonism Anti PCP can induce the decrease of gamma shock energy in the prefrontal cortex of cynomolgus. The low dose DA receptor agonist bromocriptine can increase the gamma oscillation power in the bilateral prefrontal cortex of chronic PCP cynomolgus, and then decrease. It may be different from the main part of the drug in different time periods. The high dose DA receptor antagonist haloperidol can be used. The increase of gamma shock power in the bilateral prefrontal frontal lobes of the chronic PCP cynomolgus monkey model may improve the cognitive related symptoms of schizophrenia, indicating that the dysfunction of the DA system plays a certain role in the cognitive impairment of schizophrenia, and the imbalance of DA, Glu and GABA constitutes the pathophysiological basis of schizophrenia.
【學位授予單位】：昆明醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R749.3

【參考文獻】

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1 陳紹琦;劉寧;鄭佳威;齊華;肖壯偉;;溴麥角隱亭誘導(dǎo)的猴幻想行為的生理學特性(英文)[J];Neuroscience Bulletin;2006年05期

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