葛根素增強學習記憶作用與中樞Septo-Hippocampal路徑之關係

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Title:	葛根素增強學習記憶作用與中樞Septo-Hippocampal路徑之關係 Facilitating Effect of Puerarin on Learning and Memory---Role of Septo-Hippocampal Pathway
Authors:	謝明村
Contributors:	中國醫藥學院藥學研究所
Keywords:	葛根素;學習記憶;被動迴避學習;細胞中隔;海馬迴;Puerarin;Learning and memory;Passive avoidance learning;Septum;Hippocampus
Date:	1999-07
Issue Date:	2010-09-06 23:33:43 (UTC+8)
Abstract:	本研究擬腹腔注射葛根素後,觀察葛根素對藥物(Scopolamine、p-chloroamphetamine、MK-801及Cycloheximide)誘發學習記憶障礙作用之影響及改善Cycloheximide誘發記憶鞏固障礙之作用機轉;其次擬於腦室給予葛根素後,觀察給予Neurotoxin:5,7-DHT(Dorsal raphe)損壞Serotonin神經元或6-OHDA (Locus coeruleus)損壞Noradrenaline神經元後之大鼠學習記憶能力,以評估septo-hippocampal路徑對於葛根素改善學習記憶作用所扮演之角色;最後,再探討Locus coeruleus給予葛根素對Cycloheximide誘發學習記憶障礙作用之影響。葛根素腹腔注射可顯著改善學習獲得障礙誘發劑P- chloroamphetamine及MK-801、記憶鞏固障礙誘發劑Cycloheximide之作用;但對Scopolamine誘發學習獲得障礙不具改善作用。其次,葛根素對記憶鞏固障礙誘發劑Cycloheximide之改善作用,可部分被膽鹼接受器Scopolamine或煙鹼接受器拮抗劑 Mecamylamine所阻斷,亦可被Serotonin釋放促進劑P-chloroamphetamine所阻斷;進一步,可被5-HT/sub 2/接受器致效劑DOI所阻斷,但突觸後5-HT/sub 1A/接受器致效劑8-OH-DPAT。葛根素腦室給藥可改善Cycloheximide誘發記憶鞏固障礙,並可改善AF64-A誘發之學習記憶能力障礙。當雙側Dorsal raphe區投與神經毒素5,7-DHT(4.mu.g/ 2.mu.l)無法阻斷腦室投與葛根素對Cycloheximide誘發記憶鞏固障礙之改善作用。另當雙側Locus coerulus區投與神經毒素6-OHDA(4 .mu.g/ 2 .mu.l)則可阻斷腦室投與葛根素對Cycloheximide誘發記憶鞏固障礙之改善作用。最後,以Ibotenic acid投與Medial septum亦可阻斷腦室投與葛根素對Cycloheximide誘發記憶鞏固障礙之改善作用。葛根素在被動迴避學習之作用,應與Septo- hippocampal路徑有關,依賴Septo-hippocampal路徑及其支配神經細胞體(Locus coerulus noradrenergic neurons)之完整性。而其作用機轉,主要作用於locus coerulus區Noradrenergic neurons,經.alpha.-及.beta.-adrenergic receptors,以調節Hippocampus區神經元之活性;其次並經由Medial septum區之Cholinergic receptors,以調節Hippocampus區神經元之活性。另對自中藥分離出之一些活性成分(n-butyldienephthalide、 ferulic acid)進行被動迴避學習測定,以評估其在學習記憶能力方面之作用。獲致成果如下:n-butyldienephthalide、Ferulic acid均可改善Cycloheximide誘發之記憶鞏固障礙,其中n-butyldienephthalide之作用較Ferulic acid為佳。 On this account, the purpose of the present study was intended to investigate the attenuating effect of puerarin on drug-induced memory impairment and the role of the septo-hippocampal pathway in the attenuating effect of puerarin. Therefore, we investigate whether puerarin (i.p. or i.c.v.) attenuate the drugs-induced memory processes impairment. Secondly, we investigate whether the attenuating effect of puerarin is antagonized by cholinergic antagonists or serotonergic agonists. Finally, we investigate whether the attenuating effect of puerarin is antagonized by intra-raphe injection of 5,7-DHT, intra-coeruleus injection of 6-OHDA, or intra-septal injection of ibotenic acid. Puerarin can attenuate the impairments of learning acquisition induced by p-chloroamphetamine (PCA) and MK-801, the impairments of memory consolidation induced by cycloheximide (CXM) in rats. In the mechanism for the counteractive effects of puerarin on CXM-induced memory consolidation impairment, the counteractive effect of HBA was depressed by either SCOP or mecamylamine. The serotonin (5-HT) releaser, PCA significantly antagonized the counteractive effect of puerarin on the CXM-induced shortening of retention latencies. Furthermore, the counteractive effect was also inhibited by the 5-HT/sub 2/ receptor agonist DOI but not by the 5-HT/sub 1A/receptor agonist 8-OHDPAT. Puerarin (i.c.v.) could attenuate the CXM-induced memory consolidation impairment and AF64A-induced memory processes impairment. The attenuating effects of puerarin (i.c.v.) on the CXM-induced memory consolidation impairment was blocked by locus coeruleus lesion induced by 6-OHDA, and by medial septal lesion induced by ibotenic acid. But dorsal raphe lesion induced by 5,7-DHT did not block the attenuating effect of puerarin. The action mechanism on the attenuating effect of puerarin might be related to septo-hippocampal pathway, dependent on the intact septo-hippocampal pathway and locus coerulus noradrenergic neurons. The attenuating effect of puerarin was due to activating the hippocampal neurons via .alpha.- and .beta.-adrenergic receptors projecting from the locus coerulus noradrenergic neuron, and via the cholinergic receptors projecting from the medial septum. Furthermore, we also investigated some active constituents from Chinese herb (such as n-butyldienephthalide and ferulic acid) on the memory functions by the passive avoidance task in rats. We found the above active constituents ameliorated the cycloheximide-induced memory consolidation impairment, and the effect of n-butyldienephthalide was better than that of ferulic acid.
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