Hyperserotonergic phenotype after monoamine oxidase inhibition in larval zebrafish

被引：98

作者：

Sallinen, Ville ^{[1
]}

Sundvik, Maria ^{[1
]}

Reenila, Ilkka ^{[2
]}

Peitsaro, Nina ^{[1
]}

Khrustalyov, Denis ^{[1
]}

Anichtchik, Oleg ^{[1
]}

Toleikyte, Gabija ^{[1
]}

Kaslin, Jan ^{[1
]}

Panula, Pertti ^{[1
]}

机构：

[1] Univ Helsinki, Ctr Neurosci, Inst Biomed Anat, FIN-00014 Helsinki, Finland

[2] Univ Helsinki, Inst Biomed Pharmacol, FIN-00014 Helsinki, Finland

来源：

JOURNAL OF NEUROCHEMISTRY | 2009年 / 109卷 / 02期

基金：

芬兰科学院;

关键词：

behavior; deprenyl; fluvoxamine; ontogeny; p-chlorophenylalanine; serotonin; DANIO-RERIO; SEROTONIN SYNDROME; MESSENGER-RNA; BRAIN; EXPRESSION; NEURONS; SYSTEMS; PATTERNS; BEHAVIOR; IDENTIFICATION;

D O I：

10.1111/j.1471-4159.2009.05986.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Serotonin (or 5-hydroxytryptamine; 5-HT) and monoamine oxidase (MAO) are involved in several physiological functions and pathological conditions. We show that the serotonergic system and its development in zebrafish are similar to those of other vertebrates rendering zebrafish a good model to study them. Development of MAO expression followed a similar time course as the 5-HT system. MAO expression and activity were located in or adjacent to serotonergic nuclei and their targets, especially in the ventral hypothalamus. MAO mRNA was detected in the brain from 24 h post-fertilization and histochemical enzyme activity from 42 h post-fertilization. Deprenyl (100 mu M) decreased MAO activity 34-74% depending on the age. Inhibition of MAO by deprenyl strongly increased 5-HT but not dopamine and noradrenaline levels. Deprenyl decreased 5-HT-immunoreactivity in serotonergic neurons and induced novel ectopic 5-HT-immunoreactivity neurons in the diencephalon in a manner dependent on 5-HT uptake. Deprenyl administration decreased locomotion, altered vertical positioning and increased heart rate. Treatment with p-chlorophenylalanine normalized 5-HT levels and rescued the behavioral alteration, indicating that the symptoms were 5-HT dependent. These findings suggest that zebrafish MAO resembles mammalian MAO A more than MAO B, metabolizing mainly 5-HT. Applications of this model of hyperserotonergism include pharmacological and genetic screenings.

引用

页码：403 / 415

页数：13

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