Role of neurotransmitters and environmental enrichment in the critical period of brain development

神经递质和环境丰富在大脑发育关键期的作用

• 批准号: 14580733
• 负责人: UEDA Shuichi
• 金额: $ 2.18万
• 依托单位: DOKKYO UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580733/
• 关键词: dentate gyrus; proliferation; water maze; HPLC; BrdU; learning hehavior; Neurogenesis; serotonin; 攻撃性; ラット; 同種攻撃; キレる子供; 海馬; 神経細胞新生; 水迷路; 細胞培養; 豊かな環境; 記憶学習

ABSTRACTThe dentate gyrus(DG) of the hippocampal formation produces new neurons throughout adulthood in mammalian species. Several experimental statuses and factors regulating neurogenesis have been identified in the adult DG. For example, exposure to an enriched environment enhances neurogenesis in the DG and improves hippocampus-dependent spatial learning. Furthermore, serotonin is known to influence adult neurogenesis, and learning and memory. However, the effects of long-lasting depletion of serotonin over the developing period on the neurogenesis have not been investigated. Thus, we examined the influence of long-lasting serotonin depletion on the environmental enrichment-induced neurogenesis and spatial memory performance. As reported previously, environmental enrichment significantly increased new neurons in the DG. However, there was no improvement of spatial learning test in adult rats in standard and in environmental enrichment housings.Intracisternal administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), on postnatal day 3 apparently reduced serotonin content in the adult hippocampus without regeneration. This experimental depletion of serotonin in the hippocampus of rats housed in an enriched environment had no effect on spatial memory performance, but produced significant decreases in the number of bromodeoxyuridine (BrdU)-labeled new cells in the DG. These findings indicate that newly generated cells stimulated by environmental enrichment are not critical for improvements in hippocampus-dependent learning. Furthermore, numbers of BrdU-labeled cells in the DG of 5,7-DHT-injected rats did not differ between 1 day and 4 weeks after BrdU injection. These data suggest that survival of newly generated DG cells remains relatively constant under long-lasting serotonin depletion.

摘要海马形成的齿状回（DG）在整个哺乳动物物种中都会产生新的神经元。在成年DG中已经确定了调节神经发生的几种实验状态和因素。例如，暴露于富集的环境会增强DG中的神经发生，并改善海马依赖性空间学习。此外，众所周知，血清素会影响成人神经发生以及学习和记忆。然而，尚未研究5-羟色胺在发育时期对神经发生的持久耗竭的影响。因此，我们研究了长效的5-羟色胺耗竭对环境富集诱导的神经发生和空间记忆性能的影响。如前所述，环境富集显着增加了DG中的新神经元。然而，在标准大鼠和环境富集外壳中，成年大鼠的空间学习测试没有改善。脑奥特纳特纳尔的血清素能神经毒素的给药，5,7-二羟基tryptamine（5,7-DHT），产后第3天，显然减少了成人Hippocampuspus的血清素含量。在富集环境中容纳大鼠海马中5-羟色胺的实验耗竭对空间记忆性能没有影响，但在DG中，溴脱氧尿苷（BRDU）标签的新细胞的数量显着减少。这些发现表明，通过环境富集刺激的新产生的细胞对于改善海马依赖性学习并不重要。此外，在BRDU注射后1天到4周之间，DG中的BRDU标记的细胞数量没有差异。这些数据表明，在持久的5-羟色胺消耗下，新生成的DG细胞的存活保持相对恒定。

项目成果

攻撃性とセロトニン

攻击性和血清素

• 发表时间: 2003
• 期刊: Clinical Neuroscience 21
• 作者: 上田秀一

Susuki K, Nishimoto Y, Yamada M, Baba M, Ueda S, Hirata K, Yuki N: "Acute motor axonal neuropathy rabbit model : immune attack on nerve root axones."Ann Neurol. 54. 383-388 (2003)

Susuki K、Nishimoto Y、Yamada M、Baba M、Ueda S、Hirata K、Yuki N：“急性运动轴突神经病兔模型：对神经根轴突的免疫攻击。”Ann Neurol。

Sakakibara, S.: "RNA-binding protein Musashi family, role for CNS stem cells and a subpopuration of ependymal cells revealed by targeted disruption and antisense ablation"Proceedings of Natonal Academy of Science of USA. 99. 15194-15199 (2002)

Sakakibara, S.：“RNA 结合蛋白 Musashi 家族，通过靶向破坏和反义消融揭示的 CNS 干细胞和室管膜细胞亚群的作用”美国国家科学院院刊。

Immunocytochemical localization of the alpha 1A subunit of the P/O-type calcium channel in the rat cerebellum.

大鼠小脑中 P/O 型钙通道的 α1A 亚基的免疫细胞化学定位。

• 发表时间: 2004
• 期刊: Eur.J.Neurosci. 19
• 作者: Kulik;A.
• 通讯作者: A.

Ueda S, Sakakibara S: "Role of serotonin in aggressive behavior."J Brain Sci. 29. 16-19 (2003)

Ueda S、Sakakibara S：“血清素在攻击行为中的作用。”J Brain Sci。