Effects of alcohol and metamphetamine on neurous system : a molecular biological study

酒精和甲基​​苯丙胺对神经系统的影响：分子生物学研究

• 批准号: 09307018
• 负责人: SUWAKI Hiroshi
• 金额: $ 24.06万
• 依托单位: Kagawa Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A).
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09307018/
• 关键词: alcoholism; acetaldehyde adducts; hippocampus; calmodulin; FAS; antihypnotism; VTA; dopamine; 離脱症; アポーシス; 逆耐性現象; GABAAレセプター; アルコール; CaM-kinase; FAS; メタンフェタミン; GABA(A)レセプター; Syaptophysin; 分子遺伝学; 大脳皮質; 覚醒剤中毒; 神経可塑性; ドーパミン神経路; 離脱; モデル

Acetaldehyde adduct seems to be a risk factor for brain damage in alcohol dependent and withdrawal animals. Furthermore, acetaldehyde adducts production and apoptosis-related gene expression in these animals were elucidated in the present study. On the other hand, abnormal formation of mossy fiber, LTP effects, strong expression of GluR2 subunit, editing of Q/R site and enzyme of CaM dependent phosphatase were observed in the hippocampus. With respect to peptides in the brain, expression of VIP-IR and DNA topoisomerase II β were apparently increased in the cerebral cortex and CA3 pyramidal cells, respectively. Calbindin D28k and GFAP-IR cells were found in the hippocampus and hypothalamus. It was of particularly interest that the expression of IR cells in the SCN of hypothalamus indicated the relationship with circadian rhythm. In FAS animals the ectopic cell mass in the cerebral cortex, abnormal distribution of mossy fibers, developmental anomaly of Purkinje and pyramidal cells and disappear of foot processes of Burgman glia cells were characteristically observed.In MAP dependent animals the neural plasticity was indicated to have relationship with arc gene, synaptophysin and α-tubulin. Additionally, the pathway of the midbrain VTA-Accumbence nucleus-Prefrontal cortex was also demonstrated to play an important role in abnormal behavior of the animals.

乙醛加合物似乎是酒精依赖和戒断动物脑损伤的危险因素。此外，本研究阐明了这些动物中乙醛加合物的产生和细胞凋亡相关基因的表达。在海马中观察到 LTP 效应、GluR2 亚基的强表达、Q/R 位点的编辑和 CaM 依赖性磷酸酶。在大脑中，大脑皮层和 CA3 锥体细胞中的 VIP-IR 和 DNA 拓扑异构酶 II β 的表达明显增加，在海马和下丘脑中发现了 GFAP-IR 细胞。下丘脑SCN中的IR细胞表明FAS动物大脑皮层异位细胞团、苔藓纤维分布异常、发育等与昼夜节律的关系。典型地观察到浦肯野细胞和锥体细胞的异常以及伯格曼胶质细胞足突的消失。在MAP依赖性动物中，神经可塑性被表明与arc基因、突触素和α-微管蛋白此外，还与中脑VTA-通路有关。伏伏核-前额皮质也被证明在动物的异常行为中发挥着重要作用。

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