Development of drugs for facilitating brain development and memory/learning

开发促进大脑发育和记忆/学习的药物

• 批准号: 13557086
• 负责人: NAKAMURA Shoji
• 金额: $ 7.1万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557086/
• 关键词: brain development; DNA tip; memory; learning; prenatal stress; neurotrophic; neurotoxic; Alzheirmer disease; 胎仔脳; 海馬; ストレス; 胎生期

In a previous study, we have found that short-lasting mild prenatal stress (restraint stress to pregnant rats, 30min/day for 3 days from E15 to E17, 30-min stress group) induces neurotrophic effects on morphology of fetal brain neurons, while long-lasting stress (4 hours/day for 3days from E15 to E17, 4-hrs stress group) causes neurotoxic changes. In addition, we have shown that the 30-min stress group reveals significantly better memory and learning performance in the adult offspring. Based on these results, using DNA tips, the present experiments were performed to identify genes which are involved in the facilitation of development of brain neurons and enhanced cognitive performance.Gene expression in three groups, control, 30-min stress and 4-hrs stress groups was investigated using 3 pieces of DNA tips (Rat Genome U34A, Affymetrix) for each group. The DNA tips used included about 8800 genes. The genes analyzed were receptors (808), channels (187), transporters (138), enzymes (1822), kinases (382), phosphatases (129), and transcription factors (57). The total RNAs extracted from the whole brain and hippocampal tissue of the fetal brains were analyzed. Gene expression was ranked for significance based on replication of data, signal intensity, statistical significance of differences among the three groups. Five to twenty genes that revealed significant increases or decreases in expression in the 30-min stress and 4-hrs stress group as compared to the control group were identified. These genes from the hippocampus included neurotrophic factors, and genes related to Alzheimer disease and neuronal guidance. It is also noted that genes showing significant changes are greatly different between the whole brain and hippocampus.

在以前的研究中，我们已经发现，短暂的轻度产前应激(对怀孕大鼠的束缚应激，从E15到E17，每天30min，应激组，30min应激组)引起神经营养效应，而长期应激(从E15到E17，每天4h，应激组，4h应激组)引起神经毒性改变。此外，我们还发现，30分钟的应激组在成年后代中表现出明显更好的记忆和学习表现。基于这些结果，本实验利用DNA TIPS技术对促进大脑神经元发育和提高认知能力的相关基因进行了研究。分别使用3条DNA TIP(大鼠基因组U34A，Affymetrix)对对照组、30min应激和4h应激3组的基因表达进行了研究。使用的DNA提示包括大约8800个基因。分析的基因包括受体(808)、通道(187)、转运体(138)、酶(1822)、激酶(382)、磷酸酶(129)和转录因子(57)。提取全脑和胎脑海马区组织的总RNA进行分析。根据数据重复、信号强度、三组间差异的统计学意义对基因表达进行显著性排序。与对照组相比，30分钟应激组和4小时应激组中有5到20个基因的表达显著增加或减少。这些来自海马体的基因包括神经营养因子，以及与阿尔茨海默病和神经指导相关的基因。还注意到，显示显著变化的基因在整个大脑和海马体之间有很大的不同。

项目成果

Fujioka, T.: "Materno-fetal coordination of stress-induced Fos expression in the hypothalamic praventricular nucleus during pregnancy"Neuroscience. 118. 409-415 (2003)

Fujioka, T.：“怀孕期间下丘脑室前核中应激诱导的 Fos 表达的母胎协调”神经科学。

Nishiike, S.: "Effect of AF644, a cholinergic neurotoxin, on footshock stimulation induced locus coeruleus excitation in rats"Neuroscience Letters. 302. 33-36 (2001)

Nishiike, S.：“AF644（一种胆碱能神经毒素）对大鼠足部电击刺激诱导的蓝斑兴奋的影响”神经科学快报。

T.Fujioka: "Mild prenatal stress enhances learning performance in the non-adopted rat offspring"Neuroscience. 103. 301-307 (2001)

T.Fujioka：“轻微的产前压力可提高非收养大鼠后代的学习表现”神经科学。

Ishikawa, A.: "Neurons in the lateral paragigantocellu ; ar nucleus projecting to the infralimbic cortex in rats : electrical activity and response to change in bloodpressure."Neuroscience Letters. 311. 57-60 (2001)

Ishikawa, A.：“外侧副巨细胞中的神经元；投射到大鼠边缘下皮层的 ar 核：电活动和对血压变化的反应。”《神经科学快报》。

Iqbal Chowdhury, G.M.: "Cortical spreading depression affects Fos expression in the hypothalamic paraventricular nucleus and the cerebral cortex of both hemispheres"Neuroscience Research. 45. 149-155 (2003)

Iqbal Chowdhury, G.M.：“皮质扩散抑制影响下丘脑室旁核和两个半球大脑皮层的 Fos 表达”神经科学研究。