Popova N K, Gilinsky M A, Amstislavskaya T G, Morosova E A, Seif I, De Maeyer E
Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia.
J Neurosci Res. 2001 Nov 1;66(3):423-7. doi: 10.1002/jnr.1234.
The effect of a lack of the gene encoding monoamine oxidase A (MAO A) in transgenic Tg8 mice on the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin (5-HT) biosynthesis, and on the levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the midbrain, hypothalamus, hippocampus, striatum, amygdala, and frontal cortex was studied. It was shown that mice with a genetic MAO A knockout differed from mice of the initial C3H/HeJ strain in having a higher level of 5-HT and a lower level of its metabolite, 5-HIAA, in all brain regions but the frontal cortex, where the changes were insignificant. Although the 5-HIAA/5-HT ratio in various brain regions differed considerably, the decrease of the 5-HT oxidative deamination index in Tg8 mice was similar in different brain regions (to 41-45% of control values), with the exception of the frontal cortex, where the decrease of the 5-HIAA/5-HT was somewhat smaller (to 54%). The presence of the remaining 45% +/- 1.9% of the control ratio value indicates rather effective oxidative deamination of 5-HT in MAO A knockout mice and explains the lack of severe behavioral and pathological consequences in MAO A genetic deficiency. An increase of TPH activity in mice lacking MAO A was found in the frontal cortex, hippocampus, and amygdala. No significant changes were found in the striatum, hypothalamus, and midbrain. The data show an effect of the MAO A gene mutation on TPH and indicate a uniform decrease of 5-HT catabolism in different brain regions except for the frontal cortex, which is somewhat more resistant to the lack of MAO A than other brain structures.
研究了转基因Tg8小鼠中缺乏单胺氧化酶A（MAO A）编码基因对色氨酸羟化酶（TPH）活性、血清素（5-HT）生物合成限速酶活性以及中脑、下丘脑、海马体、纹状体、杏仁核和额叶皮质中5-HT和5-羟基吲哚乙酸（5-HIAA）水平的影响。结果表明，基因敲除MAO A的小鼠与初始C3H/HeJ品系小鼠不同，在除额叶皮质外的所有脑区中，5-HT水平较高，其代谢产物5-HIAA水平较低，而额叶皮质中的变化不显著。尽管不同脑区的5-HIAA/5-HT比值差异很大，但Tg8小鼠中5-HT氧化脱氨指数在不同脑区的降低情况相似（降至对照值的41-45%），额叶皮质除外，该脑区5-HIAA/5-HT的降低幅度稍小（降至54%）。对照比值剩余45%±1.9%的存在表明MAO A基因敲除小鼠中5-HT的氧化脱氨相当有效，并解释了MAO A基因缺陷中缺乏严重行为和病理后果的原因。在缺乏MAO A的小鼠中，额叶皮质、海马体和杏仁核中的TPH活性增加。纹状体、下丘脑和中脑未发现显著变化。数据显示MAO A基因突变对TPH有影响，并表明除额叶皮质外，不同脑区的5-HT分解代谢均有一致降低，额叶皮质比其他脑结构对缺乏MAO A的耐受性稍强。
