不同强度脑电场刺激对抑郁大鼠额叶单胺类递质含量的影响

目的:探讨不同强度脑电场刺激对抑郁大鼠额叶单胺类递质含量的影响。方法:建立Wistar大鼠抑郁症模型;分别在模型大鼠双侧颅骨大脑额叶区放置刺激电极(国家发明专利号ZL01103273.1)并固定,应用脑电场刺激仪给予不同强度脑电场刺激,刺激频率30Hz,刺激波形为正弦波,刺激持续时间1h。应用荧光分光光度法分别测定大鼠额叶脑组织内5羟色胺(5-HT)、去甲肾上腺素(NE)和多巴胺(DA)含量。结果:与正常对照组比,模型对照组大鼠5-HT及NE明显下降(分别P<0.001),治疗对照组单胺类递质无明显变化(分别P>0.05)。低强度治疗组治疗1h后,DA、5-HT及NE含量均无明显改变(分别P>0.05),中等强度治疗组及高强度模型治疗组大鼠额叶脑组织内5-HT及NE含量出现显著增高(分别P<0.05,P<0.01)。结论:一定强度的脑电场刺激可显著提高额叶内单胺类递质的含量,对抑郁症可能提示具有治疗作用。     

不同程度颈动脉狭窄大鼠模型建立及脑内单胺类递质变化的研究

周振华,陈康宁,黄河清,周宇,范文辉,李露斯摘要:目的制作一种新的不同狭窄程度的大鼠颈动脉狭窄模型,观察重度颈动脉狭窄大鼠学习能力及脑内单胺类神经递质含量的变化。方法采用“针控线拴法”,通过调整针的型号来制作不同狭窄程度的大鼠颈动脉狭窄模型,观察重度颈动脉狭窄大鼠水迷宫定位航行试验并用高效液相色谱法测定大鼠脑内单胺类神经递质含量的变化。结果成功制作了轻、中、重不同狭窄的颈动脉狭窄模型;各时相点水迷宫定位航行试验中重度颈动脉狭窄大鼠较假手术对照组逃避潜伏期明显延长(P<0.01);除1月、2月重度颈动脉狭窄组DA与假手术对照组相比无显著性差异外(P>0.05),其余时相点重度颈动脉狭窄组NE、5-HT、DA含量与假手术对照组相比均显著降低(P<0.01)。结论针控线拴法能成功建立不同狭窄程度的大鼠颈动脉狭窄模型,重度颈动脉狭窄大鼠学习能力受损且脑内单胺类神经递质含量降低。     

小柴胡汤改善抑郁症状及相关神经递质与神经营养因子分析

目的探索小柴胡汤对抑郁症状患者的疗效及脑内神经递质、神经营养因子变化关系。方法选取2013年4月~2015年4月于我院治疗的抑郁症状患者共计96例进行研究。按照入院顺序分为观察组和对照组,观察组患者应用小柴胡汤进行治疗,对照组患者应用西药进行治疗。观察两组患者治疗后的临床疗效及脑内神经递质、神经营养因子的变化。结果在接受治疗后,观察组患者的临床疗效显著,其总有效率达87.5%,明显高于对照组治疗后的总有效率41.67%,两组比较差异具有统计学意义(P0.05)。两组患者在接受治疗后均出现不同情况的副作用,但是观察组的不良反应发生率(4.17%)明显少于对照组的不良反应发生率(58.33%),两组比较差异具有统计学意义(P0.05);患者在应用小柴胡汤治疗后,两组患者的Ach、5-HT、NE及DA值在治疗前后差异具统计学意义(P0.05),且在5-HT、NE及DA值方面,观察组较对照组变化更显著,在Ach上,两组患者治疗效果无显著统计学差异(P0.05);两组患者治疗前后神经营养因子变化情况差异具有统计学意义(P0.05),观察组患者的神经营养因子的变化较对照组更大。结论小柴胡汤治疗抑郁症状的临床疗效显著,有抗抑郁作用,并对脑内神经递质、神经营养因子有一定的影响。     

粉防己碱和还原型谷胱甘肽治疗帕金森病大鼠模型的实验研究

目的 观察粉防己碱合用还原型谷胱甘肽对帕金森病(Parkinson's disease,PD)大鼠模型脑内多巴胺及代谢产物的影响并探讨其作用机制.方法 采用6-羟基多巴立体定向注射制作PD大鼠模型,将成功模型随机分为4组未治疗组(生理盐水)组,谷胱甘肽加粉防己碱(GSH Tet)组,谷胱甘肽(GSH)组,左旋多巴(L-dopa)组及正常对照组,分别腹腔注射上述药物共50 d,给药结束后观察大鼠旋转行为,测定各组大鼠脑纹状体单胺氧化酶B(MAO-B),高效液相色谱-电化学仪测定纹状体多巴胺(DA),高香草酸(HVA),3,4-二羟基苯乙酸(DOPAC)水平及DA的代谢率(HVA/DA).结果 ①GSH合用Tet能显著改善模型大鼠旋转行为[(7.72±2.05)r/min vs (12.39±3.20)r/min,P＜0.05].②GSH Tet组的DA、HVA、DOPAC含量明显高于其他对照组,且其DA,HVA含量与GSH组比较有统计学差异(P＜0.05).③GSH Tet组的HVA/DA(11.48±1.08)及MAO-B活性[(10.5±2.50)U/h/mgprot]明显低于其他治疗组,与GSH组比较均有统计学差异(P＜0.05).结论 粉防己碱合用还原型谷胱甘肽能增强对PD大鼠的神经保护作用.     

非痴呆性血管性认知功能障碍患者的脑电超慢涨落图表现

目的探讨主诉记忆力减退的非痴呆性血管性认知功能障碍(VCIND)患者脑内神经递质活动的变化及意义。方法选择2008—2012年第二炮兵总医院神经内科门诊患者716例,其中主诉记忆力减退的VCIND组370例,正常对照组346例。采用简易精神状态量表(MMSE)、蒙特利尔认知测评量表(MoCA)进行认知评估。应用脑电超慢涨落(EFG)分析仪测定S1γ-氨基丁酸(GABA)、S2谷氨酸(Glu)、S4 5-羟色胺(5-HT)、S5乙酰胆碱(Ach)、S7去甲肾上腺素(NE)、S11多巴胺(DA)等脑神经递质的活动。结果观察组GLU、5-HT的活动存在异常,GLU显著高于对照组(P<0.05),5-HT显著低于对照组(P<0.05);GABA、Ach、NE、DA的活动与对照组比较,差异无统计学意义(P>0.05)。结论主诉记忆力减退的VCIND人群脑内神经递质谷氨酸、5-羟色胺活动异常。EFG分析可作为一种有效的VCIND辅助诊断方法。     

香兰素吸嗅对大鼠抑郁样行为及脑单胺类神经递质的影响

目的研究香兰素吸嗅对大鼠抑郁样行为改善及其机制。方法慢性不可预见性中等强度应激(CUMS)+孤养的方法建立大鼠抑郁症模型。为验证香兰素作用途径,另设立大鼠嗅球毁损(OBX)模型。于造模前、后及干预后4 w测试大鼠糖水消耗量和强迫游泳不动时间,干预结束后超高压液相色谱检测大鼠脑内5-HT、DA、NE的量。结果与造模后相比,CUMS+香兰素吸嗅组大鼠神经行为学指标显著好转(P<0.05);其脑匀浆液5-HT、DA的量显著高于空白对照组(P<0.05)。与造模后相比OBX+香兰素吸嗅组大鼠神经行为学指标未见好转(P>0.05);其脑匀浆液5-HT、DA、NE均显著低于假手术组(P<0.05)。结论香兰素可经嗅觉通路改善大鼠抑郁样行为,其机制可能通过提升脑内5-HT、DA实现的。     

抑郁症患者中枢神经递质活动的脑电超慢涨落图分析

目的探讨抑郁症患者的脑电超慢涨落图(Encephalofluctuograph,EFG)的特征。方法对符合《中国精神障碍与诊断标准(第3版)》(CCMD-3)抑郁症诊断标准的51例门诊及住院抑郁症患者,采用EFG分析仪检测其中枢神经递质活动变化情况及其脑功能状态,与正常对照组进行比较。结果抑郁症患者中枢神经递质γ-氨基丁酸(GABA)、谷氨酸(Glu)、5-羟色胺(5-HT)、乙酰胆碱(Ach)、去甲肾上腺素(NE)及多巴胺(DA)等功率的实测值都低于正常对照组,差异均有统计学意义(P均0.05)。相对功率5-HT明显升高而DA的相对功率明显下降(P0.05)。脑功能状态指数中的运动指数下降,差异有统计学意义(P0.05),而兴奋抑制指数和血管舒缩指数的实测值差异无统计学意义(P0.05)。结论抑郁症患者脑内主要神经递质功率均明显降低,其脑功能状态存在不同程度的异常。     

静安口服液对小儿多发性抽动症中枢神经递质的影响

目的：探讨静安口服液对小儿多发性抽动症中枢神经递质的影响。方法选择我院2010‐04—2013‐01收治的61例小儿多发性抽动症为研究对象,将其随机分为实验组和对照组,并选取30名健康儿童为健康对照组。实验组采用静安口服液治疗,对照组采用硫必利片剂治疗。比较3组氨基酸类神经递质和单胺类神经递质水平。结果组内比较发现,实验组治疗后NE和GABA水平上升,GLU、HVA和5‐HT水平降低,与治疗前比较差异有统计学意义（P＜0.05）。对照组治疗后GLU、ASP、5‐HT和DA水平降低,GABA和NE水平增高,与治疗前比较差异有统计学意义（P＜0.05）。与健康对照组相比,实验组和对照组治疗前ASP、GLU、HVA和5‐HT水平均明显增高,GABA水平较低,差异有统计学意义（P＜0.05）。但2组患者治疗前后各指标比较差异无统计学意义（ P＞0.05）。结论中枢神经递质失衡与小儿多发性抽动症存在密切关联,而静安口服液可有效改善各神经递质水平。     

慢性应激对大鼠认知及脑脊液单胺类神经递质的影响

目的探讨慢性应激对大鼠脑单胺类神经递质以及认知功能影响的研究。方法75只SD大鼠随机分为对照组(25只)和慢性应激组(50只),后者以束缚浸水应激方式连续应激21天,每日记录大鼠体重及进食量并进行两组比较,三周后行水迷宫实验、大鼠脑单胺类神经递质测定。结果(1)应激组大鼠体重的增加、进食量较对照组明显减少(P<0.05);(2)水迷宫实验:应激组大鼠的游出时间较对照组明显增加(P<0.05),但错误次数无明显差异(P>0.05)。(3)大鼠脑脊液单胺类神经递质含量(ug/L):5-HT、5-HIAA及MHPG的含量应激组明显低于对照组(P<0.05),NA、DA及HVA在应激组均为升高,但无显著差异(P>0.05)。结论慢性束缚浸水应激三周使大鼠脑脊液中5-HT、5-HIAA及MHPG的含量降低,但对认知功能无明显影响。     

抑郁症患者脑电超慢涨落检测分析

目的:探讨抑郁症患者脑内神经递质活动变化。方法:应用中国北京ML2001脑电超慢涨落分析仪,通过对14例抑郁症患者于治疗前及治疗2、4周后脑电超慢涨落图(EFG),分析其谱线变化来反映脑内神经递质活动变化。结果:14例抑郁症患者治疗前脑内神经递质值与正常值对照比较,其5羟色胺(5HT)、乙酰胆碱(ACh)、去甲肾上腺素(NE)、多巴胺(DA)均降低,但以ACh、DA差异有显著性。治疗前及抗抑郁药治疗2、4周EFG值比较,其γ氨基丁酸(GABA)、谷氨酸(Glu)明显降低,而5HT、ACh、DA显著升高,差异有显著性。结论:脑内神经递质GABA、Glu、5HT、ACh、NE、DA间的协同不良可能导致了抑郁症发作,抗抑郁药治疗后脑内神经递质变化较大,单胺类递质活性增强。     

脑梗死后遗症大鼠模型脑组织ATP、ADP及单胺类神经递质含量的变化

目的 研究脑梗死后遗症大鼠模型脑组织ATP、ADP及单胺类神经递质含量的变化。方法 建立脑梗死后遗症大鼠模型，用高效液相色谱（HPLC）法测定大鼠脑组织ATP、ADP及单胺类神经递质含量。结果 刺激组（SG）毛发相对黯淡无光、卷曲，精神萎靡，惊恐，消瘦，肢体无力，摄食减少，饮水减少，手术伤口愈合迟缓，符合中医脑梗死后遗症征候。正常组（NG）大鼠脑组织ATP、ADP含量显著高于SG组、术后不刺激组（SG）（P〈0．01），同时NSG组大鼠脑组织ATP、ADP含量显著高于SG组（P〈0．05）。SG组大鼠脑组织NE、DA和5-HT含量显著低于NG组（P〈0．01），NSG组（P〈0．05）；NSG组大鼠脑组织DA含量显著低于NG组（P〈0．05）。结论 脑梗死后遗症大鼠由于能量代谢障碍而出现脑组织的ATP、ADP含量降低，并且伴有大脑释放单胺类递质增加及脑细胞内的单胺类递质含量减少，单胺类递质分泌增加又加重了脑组织的损伤，加剧ATP、ADP等能量物质代谢障碍，形成恶性循环。     

Differential vulnerability of male versus female rats to long-term effects of birth insult on brain catecholamine levels

There are gender differences in the prevalence and severity of several human behavioral disorders, in which both obstetric complications and dysregulation of brain monoamine systems have been implicated. In animal studies, males are more susceptible than are females to lasting behavioral deficits following various perinatal insults. The current study compared monoamine levels in brain regions from adult male and female rats that had been born under various conditions-vaginal birth (control), Caesarean section (C-section), or C-section with 15 min of added anoxia (Anoxia). At adulthood, male rats born by C-section had increased dopamine (DA) levels in the nucleus accumbens and dorsal striatum, and decreased amygdalar norepinephrine (NE), compared to vaginally born males. C-sectioned female rats had increased NE levels in the thalamus in comparison to vaginally born females. The only monoamine change observed in the Anoxia groups was a decrease in nucleus accumbens NE in females. Thus addition of 15 min of anoxia to the C-section procedure reversed several of the monoamine changes produced by C-section alone. Birth group had no effect on serotonin in several brain regions in either sex. Male, but not female, rats born by C-section had decreased plasma epinephrine levels at birth and slightly increased brain lactate at 5 h after birth. Pups of both sexes in the Anoxia groups had high levels of plasma catecholamines at birth. The possible functional significance of the lasting, region-specific changes in brain DA and NE due to birth insult and possible roles of hormones at birth in producing these monoamine changes in the two sexes are discussed.     

Yohimbine-induced alterations of monoamine metabolism in the spontaneously hypertensive rat of the Okamoto strain (SHR). II. The central nervous system (CNS)

Steady state levels of monoamine neurotransmitters were examined in SHR, a genetic model of hypertension and compared to its normotensive control (WKY). SHR and WKY were also challenged with alpha 2-adrenergic antagonists, (yohimbine, YOH, idazoxan) or an alpha 1-antagonist (prazosin) and alterations in CNS monoamine metabolism evaluated. SHR were found to have elevated levels of NE and 5-HT in a number of brain regions involved in cardiovascular control when compared to WKY. DA levels and metabolism were also altered in the SHR. Blockade of alpha 2-adrenoceptors and other direct and indirect actions of YOH exacerbated the abnormalities in central monoaminergic neurotransmission in SHR. Significant decreases in NE content were produced by YOH or idazoxan treatment in both SHR and WKY, presumably the result of the inhibition of alpha 2-adrenoceptor medicated presynaptic control of NE release. YOH treatment abolished the differences in steady state levels of NE between SHR and WKY, however, idazoxan did not. YOH administration resulted in significant increases in DA and 5-HT in a number of brain regions of both SHR and WKY. Idazoxan or prazosin produced few changes in DA and 5-HT metabolism except for increases in DA content in the spinal cord and brainstem of SHR given idazoxan. The YOH-induced increases in DA and 5-HT content of SHR were of a greater magnitude than the WKY in several brain regions. DOPAC levels were significantly elevated by YOH in both WKY and SHR, reflecting the antidopaminergic properties of YOH. 5-HIAA content was significantly reduced by YOH in a number of brain regions in both SHR and WKY, however, this effect was attenuated in several brain regions in SHR. The results of the present study demonstrate the multifarious nature of the alterations in CNS monoamine metabolism in SHR.     

神经生长因子对新生大鼠缺氧／缺血性脑损伤远期智能的影响

目的 探讨神经生长因子（NGF）对新生大鼠缺氧／缺血性脑损伤（HIBD）后远期智能的影响。方法 建立新生大鼠缺氧／缺血性脑损伤模型,分别给予NGF0．01mg/10g（小剂量组）和0．03mg/10g（大剂量组）腹腔注射,有用迷宫实验观察大鼠远期学习记忆能力的改变,用高效液相色谱电化学测定单胺类递质的改变。结果 NGF组（小剂量组、大剂量组）学习记忆功能明显好于对照组,表现在达标所需反映次数明显低于对照组（P＜0．05）,而正确率却明显高于对照组（P＜0．05）;小剂量NGF组与大剂量NGF组相比上述指标的改变也有显著性差异（P＜0．05）;NGF组去甲肾上腺素（NE）、高香草酸（HVA）、5－羟色胺（5－HT）等单胺类递质含量显著低于对照组（P＜0．01）。NGF组脑部改变不明显,仅见轻微的脑皮层萎缩;对照组大鼠脑部可见皮层萎缩、液化及空洞形成,病理组织学可见筛状软化灶形成,胶质结节和钙化灶的形成等。结论 NGF可预防和治疗新生大鼠缺氧／缺血性脑病所致的智能障碍,还可以减轻HIBD时单胺类神经递质的代谢紊乱而促进其智能障碍的恢复。     

Modification of dopamine and norepinephrine metabolism in the rat brain by monoamine oxidase inhibitors

Summary The treatment of Sprague-Dawley rats with monoamine oxidase (MAO) inhibitors (pargyline, tranylcypromine) profoundly affects dopamine (DA) and norepinephrine (NE) metabolism in the brain. In these rats injection of L-dopa led to large increases in norepinephrine (NE), normetanephrine (NMN) and 3-methoxytyramine (3-MT) in brain tissues. The response of MAO-inhibited rats to L-dopa contrasted sharply with those not treated with the MAO inhibitor; the latter showed no change in NE, NMN and 3-MT after similar administration of L-dopa. The increase of NE in pargyline-treated rats correlated closely with that of DA in the hypothalamus and in the brain stem. This response was greatly diminished in rats previously treated with the neurotoxin 6-hydroxydopamine, but was restored when the treatment with 6-hydroxydopamine was accompanied by desimipramine. This suggests that noradrenergic neurons were the origin of the NE response. The NMN and 3-MT increases occurring only in the rats treated with a MAO inhibitor were highly correlated. The results suggested that MAO inhibitor may affect entry of DA into catecholaminergic storage where NE synthesis takes place and from where DA is released.     

急性脑卒中后焦虑抑郁共病状态血清单胺类递质的变化研究

目的探讨急性脑卒中后焦虑抑郁共病患者血清单胺类递质水平的关系。方法采用荧光分光光度计法测定33例急性卒中后焦虑抑郁共病患者、22例急性卒中后抑郁患者、49例卒中后非焦虑抑郁患者及37例正常人血清单胺类递质的水平。结果急性脑卒中后焦虑抑郁共病组和PSD组血清中，NE、5-HT、DA含量低于非焦虑抑郁组和对照组，共病组NE、5-HT高于抑郁组，其中5-HT差异有显著意义，而非焦虑抑郁组血清中，单胺类递质的含量亦低于对照组。而大脑左侧及前部卒中患者的血清中单胺类递质水平低于其它卒中部位患者（P〈0．05）。结论急性脑卒中后焦虑抑郁共病组和单纯PSD的发生与血清中单胺类神经递质的降低有关。     

立体定向毁损大鼠杏仁核及隔核对脑内单胺类递质含量的影响

目的 :探讨杏仁核及隔核毁损后AMP模型大鼠脑内单胺类递质含量的变化。方法 :经腹腔注射苯丙胺 (amphetamine ,AMP)制作精神分裂症动物模型 ,用立体定向技术电极毁损大鼠杏仁核及隔核 ,采用荧光分光光度法和放射免疫法测定大鼠前额叶、间脑和脑干多巴胺 (DA)、5 羟色胺 ( 5 HT)和去甲肾上腺素 (NE)的含量。结果 :杏仁核及隔核毁损组前额叶DA低于模型组 (P <0 0 1) ,5 HT、NE均高于模型组 (P <0 0 1) ;杏仁核及隔核毁损组间脑DA、NE均低于模型组 (P <0 0 1) ,5 HT高于模型组 (P <0 0 1) ;脑干DA、NE均低于模型组 (P <0 0 1) ,5 HT高于模型组 (P <0 0 1)。结论 :AMP模型大鼠前额叶和脑干DA含量增高、5 HT和NE含量下降 ,间脑DA、NE含量增高、5 HT含量下降 ,立体定向毁损杏仁核及隔核能够改变脑内单胺类递质的水平。     

帕罗西汀与阿米替林联用对卒中后抑郁大鼠额前皮质区与海马区的单胺类递质、脑源性神经营养因子水平的改变

目的 探究帕罗西汀与阿米替林联用对脑卒中后抑郁(post-stroke depression,PSD)大鼠额前皮质区与海马区的单胺类递质、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)水平的影响.方法 SD大鼠被分为4组,即对照组、PSD组、帕罗西汀(Par)组和帕罗...     

Effects of neonatal rat Borna disease virus (BDV) infection on the postnatal development of the brain monoaminergic systems

Effects of neonatal Borna disease virus infection (BDV) on the postnatal development of brain monoaminergic systems in rats were studied. Tissue content of norepinephrine (NE), dopamine (DA) and its metabolite, 3,4-dihydroxyphenol acetic acid (DOPAC), and serotonin (5-HT) and its metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA) were assayed by means of HPLC-EC in frontal cortex, cerebellum, hippocampus, hypothalamus and striatum of neonatally BDV-infected and sham-inoculated male Lewis rats of 8, 14, 21, 60 and 90 days of age. Both NE and 5-HT concentrations were significantly affected by neonatal BDV infection. The cortical and cerebellar levels of NE and 5-HT were significantly greater in BDV-infected rats than control animals at postnatal days (PND) 60 and 90. Tissue content of NE in hippocampus was unaffected. In hippocampus, neonatally BDV-infected rats had lower 5-HT levels at PND 8 and significantly elevated levels at PND 21 and onwards. Neither striatal levels of 5-HT nor hypothalamic levels of 5-HT and NE were affected by neonatal BDV infection, suggesting that the monoamine systems in the prenatally maturing brain regions are less sensitive to effects of neonatal viral infection. 5-HIAA/5-HT ratio was not altered in BDV-infected rats indicating no changes in the 5-HT turnover in the brain regions damaged by the virus. Neither DA nor DOPAC/DA ratio was affected by neonatal BDV infection in any of the brain regions examined. The present data demonstrate significant and specific alterations in monoaminergic systems in neonatally BDV-infected rats. This pattern of changes is consistent with the previously reported behavioral abnormalities resulting from neonatal BDV infection.