Change of cholinergic transmission and memory deficiency induced by injection of b-amyloid protein into NBM of rats

The change of cholinergic transmission of b-amyloid protein (b-AP) treated rats was studied by intracerebral microdialysis sampling combined with HPLC analysis. b-AP1-40 was injected into nucleus basalis magnocellularis (NBM). Passive avoidance response test (step-down test) and delayed alternation task were used for memory testing. The impairment of memory after injection of b-AP1-40 into NBM exhibited mainly the deficiency of short-term working memory. One week after injection of b-AP1-40 the release of acetylcholine (ACh) from frontal cortex of freely-moving rats decreased significantly, and the response of cholinergic nerve ending to the action of high [K+] solution was rather weak. In control animals the percentage of increase of ACh- release during behavioral performance was 57%, while in b-AP1-40 - treated rats it was 34%. The temporary in-crease of the ACh-release of the rat put into a new place was also significantly diminished in b-AP1-40 -treated rats. The results show that the injection of b-AP1-40 into NBM impairs the cholinergic transmission in frontal cortex, and the impairment of cholinergic transmission may be the main cause of the deficit of working memory.     

谷氨酸是哺乳动物中枢的一种神经递质

哺乳动物中枢存在高亲和摄取谷氨酸(Glu)和门冬氨酸(Asp)系统。Glu 突触前定位于特异的神经元,生理性刺激能使 Glu 从突触前膜释出,作用于酸性氨基酸的受体,引起突触后的反应,而且具有迅速终止递质作用的机制。外源性给予 Glu 及其摹拟剂,能产生与内源性 Glu 相同的效应,同样可被受体拮抗剂阻断。Glu 具备神经递质必需的条件,是哺乳动物中枢的兴奋性递质。     

5,6-DHT损毁大鼠蓝斑内5-HT能神经末梢对电针镇痛的影响

在大鼠蓝斑注射5.6-DHT 以破坏其5-HT 末梢,然后观察电针镇痛效应的变化。动物分注药组和对照组,注药组在注射5.6-DHT 后7天,针刺镇痛效应比注药前显著下降。与此同时,蓝斑内的5-HT 末梢发生变性,产生逆行性荧光积累,从荧光积累的末梢走向来看,蓝斑内被5.6-DHT 损毁的5-HT 末梢主要来源于中缝背核。随着蓝斑内5-HT 末梢的变性,脑桥区5-HT 含量下降,下降率达27%P<0.01。对照组动物,蓝斑内5-HT 末梢保持正常,其镇痛效应与注药前相比也无明显改变。鉴于一般认为蓝斑核的活动削弱针刺镇痛效应,以上结果提示,在电针镇痛过程中,支配蓝斑的5-HT 神经末梢,对该核 NA 能神经元可能有抑制性影响。     

Change of cholinergic transmission and memory deficiency induced by injection of β-amyloid protein into NBM of rats

The change of cholinergic transmission of p-amyloid protein (P-AP) treated rats was studied by intracerebral microdialysis sampling combined with HPLC analysis. β-AP1-40 was injected into nucleus basalis magnocellularis (NBM). Passive avoidance response test (step-down test) and delayed alternation task were used for memory testing. The impairment of memory after injection of β-AP1-40 into NBM exhibited mainly the deficiency of short-term working memory. One week after injection of β-AP1-40 the release of acetylcholine (ACh) from frontal cortex of freely-moving rats decreased significantly, and the response of cholinergic nerve ending to the action of high [K+] solution was rather weak. In control animals the percentage of increase of ACh-release during behavioral performance was 57%, while in β-AP1-40-treated rats it was 34%. The temporary increase of the ACh-release of the rat put into a new place was also significantly diminished in β-AP1-40 -treated rats. The results show that the injection of      

β-淀粉样蛋白注入大鼠NBM引起的胆碱能传递变化及记忆损伤

在以β-淀粉样蛋白(β-amyloid protein,β-AP)注入基底巨细胞核(nucleus basalis magnocellularis, NBM)造成记忆功能缺损的大鼠上,用脑内微透析采样结合高效液相分析技术研究了其额叶皮层胆碱能传递的变化.记忆能力的测试采用了一次性被动回避平台测试和食物性交互延缓任务.结果表明,将β-AP_1~40注入NBM引起的记忆功能损伤,主要表现为短时工作记忆能力的减退.在向NBM内注入β-AP_1~40 1周后,自由活动大鼠额叶皮层的乙酰胆碱(ACh)释放明显减少,额叶皮层的胆碱能末梢对高钾溶液的反应也减弱.正常大鼠在行为测试过程中额叶皮层的ACh释放可增加约57%,而NBM内注入β-AP_1~40的大鼠只增加34％.当NBM内注入β-AP_1~40大鼠被放到全新环境中,其额叶皮层的胆碱释放的瞬时增加明显减少.上述实验结果表明,将β-AP_1~40注入NBM内损伤了额叶皮层胆碱能传递功能,而这种胆碱能传递功能的损伤很可能是造成短时工作记忆能力减退的原因.     

大鼠中缝背核内γ-氨基丁酸加强针刺镇痛作用

本实验中,将γ-氨基丁酸(GABA)的受体激动剂异鹅羔胺(Mus)、受体拮抗剂荷苞牡丹碱(Bicu)、神经元摄取的阻断剂哌啶酸(Nip)和GABA合成酶抑制剂3-巯基丙酸(3-MPA)经埋植的引导管注入大鼠中缝背核,注射剂量均为 4μg/μl;并观察了上述注药对动物痛阈和针刺镇痛效应的影响。 脑内注射Mus和Nip 均能明显提高动物的痛阈( 20％— 40％,P<0.05和P<0.01)和加强针刺镇痛作用;这种增强作用至少能维持2h。脑内注射Bicu和3-MPA均不影响动物的痛阈(P>0.05),但是它们都能明显地降低针刺镇痛效应(P<0.05和P<0.01)。以上结果表明,中缝背核内的GABA递质在针刺镇痛中起着一定作用。     

γ-氨基丁酸的发现史

γ-氨基丁酸(GABA)被鉴别为抑制性神经递质的事实启示人们:一些简单的氨基酸分子可以在中枢信息传递中起重要作用。本文仅就GABA 的发现、被确认是哺乳动物中枢神经递质的过程作一简介。一、哺乳动物中枢GABA 的发现GABA 作为一种化学物质来说,早在1883年已被人工合成。其后又做过一些在真菌、细菌和植物中代谢的研究。直到1950年,Roberts 和Awapara 各自发现了GABA 存在     

哺乳动物中枢单胺类递质的昼夜节律性变化

昼夜节律是生物体对昼夜交替的外环境的一种反应。哺乳动物中枢单胺类递质的代谢,在24h内呈现有规律的周期性变化。八十年代初,肾上腺素α,β受体数量昼夜节律的发现,启示精神药理学家,从时间生物学的角度去探索某些精神病的发病原因和精神药物的作用机理。现在虽已明确,视交叉上核团对机体昼夜节律的发生和消长起着重要作用;但对昼夜节律的产生机制仍不清楚。     

邻苯二甲醛衍生化高效液相色谱法分析脑氨基酸

本实验用邻苯二甲醛-β-巯基乙醇衍生化、反相梯度洗脱、荧光检测分析法测定豚鼠脑的氨基酸。60min内可测20种氨基酸。脑组织样本的预处理简单,平均回收率达95％。氨基酸保留时间的变异系数平均为1.1±0.3％(均值±标准差);峰面积的变异系数平均为2.9+0.8％;在10pmol—2nmol范围内,线性关系的相关系数平均为0.987±0.009。本文并对实验所用的色谱条件作了讨论。