Comprehensive behavioral analysis and quantification of brain free amino acids of C57BL/6J congenic mice carrying the 1473G allele in tryptophan hydroxylase-2

Hisatsugu Koshimizu, Nao Hirata, Keizo Takao, Keiko Toyama, Takashi Ichinose, Shigeki Furuya, Tsuyoshi Miyakawa

Research output: Contribution to journalArticle

Abstract

Aim: Tryptophan hydroxylase 2 (Tph2) is a rate-limiting enzyme for the biosynthesis of 5-hydroxytryptamine (5-HT, serotonin). Previous studies have reported that C1473G polymorphism of the murine Tph2 gene leads to decreased 5-HT levels in the brain and abnormal behavioral phenotypes, such as impaired anxiety- and depression-like behaviors. In this study, to confirm the effect of the C1473G polymorphism on mouse phenotypes, we conducted a comprehensive battery of behavioral tests and measured the amounts of brain free amino acids involved in the production of 5-HT. Methods: We obtained C57BL/6J congenic mice that were homozygous for the 1473G allele of Tph2 (1473G) and subjected them and their wild-type littermates (1473C) to a battery of behavioral tests. Using reverse-phase high-performance liquid chromatography (HPLC), we measured the amounts of free amino acids in the 5-HT and epinephrine synthetic/metabolic pathways in the frontal cortex, hippocampus, striatum, and midbrain. Results: We failed to detect significant differences between genotypes in depression-like behaviors, anxiety-like behaviors, social behaviors, sensorimotor gaiting, or learning and memory, while 1473G mice exhibited a nominally significant impairment in gait analysis, which failed to reach study-wide significance. In the HPLC analysis, there were no significant differences in the amounts of 5-HT, dopamine, norepinephrine, and epinephrine in the frontal cortex, hippocampus, striatum, and midbrain. Conclusion: Our findings do not support the idea that congenic C57BL/6J mice carrying the 1473G allele may represent an animal model of mood disorder under normal conditions without stress.

Original languageEnglish
Pages (from-to)56-60
Number of pages5
JournalNeuropsychopharmacology Reports
Volume39
Issue number1
DOIs
Publication statusPublished - 01-03-2019

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Congenic Mice
Tryptophan Hydroxylase
Serotonin
Alleles
Amino Acids
Brain
Frontal Lobe
Mesencephalon
Epinephrine
Hippocampus
Anxiety
High Pressure Liquid Chromatography
Depression
Phenotype
Social Behavior
Reverse-Phase Chromatography
Metabolic Networks and Pathways
Mood Disorders
Gait
Inbred C57BL Mouse

All Science Journal Classification (ASJC) codes

  • Clinical Psychology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

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title = "Comprehensive behavioral analysis and quantification of brain free amino acids of C57BL/6J congenic mice carrying the 1473G allele in tryptophan hydroxylase-2",
abstract = "Aim: Tryptophan hydroxylase 2 (Tph2) is a rate-limiting enzyme for the biosynthesis of 5-hydroxytryptamine (5-HT, serotonin). Previous studies have reported that C1473G polymorphism of the murine Tph2 gene leads to decreased 5-HT levels in the brain and abnormal behavioral phenotypes, such as impaired anxiety- and depression-like behaviors. In this study, to confirm the effect of the C1473G polymorphism on mouse phenotypes, we conducted a comprehensive battery of behavioral tests and measured the amounts of brain free amino acids involved in the production of 5-HT. Methods: We obtained C57BL/6J congenic mice that were homozygous for the 1473G allele of Tph2 (1473G) and subjected them and their wild-type littermates (1473C) to a battery of behavioral tests. Using reverse-phase high-performance liquid chromatography (HPLC), we measured the amounts of free amino acids in the 5-HT and epinephrine synthetic/metabolic pathways in the frontal cortex, hippocampus, striatum, and midbrain. Results: We failed to detect significant differences between genotypes in depression-like behaviors, anxiety-like behaviors, social behaviors, sensorimotor gaiting, or learning and memory, while 1473G mice exhibited a nominally significant impairment in gait analysis, which failed to reach study-wide significance. In the HPLC analysis, there were no significant differences in the amounts of 5-HT, dopamine, norepinephrine, and epinephrine in the frontal cortex, hippocampus, striatum, and midbrain. Conclusion: Our findings do not support the idea that congenic C57BL/6J mice carrying the 1473G allele may represent an animal model of mood disorder under normal conditions without stress.",
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Comprehensive behavioral analysis and quantification of brain free amino acids of C57BL/6J congenic mice carrying the 1473G allele in tryptophan hydroxylase-2. / Koshimizu, Hisatsugu; Hirata, Nao; Takao, Keizo; Toyama, Keiko; Ichinose, Takashi; Furuya, Shigeki; Miyakawa, Tsuyoshi.

In: Neuropsychopharmacology Reports, Vol. 39, No. 1, 01.03.2019, p. 56-60.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Comprehensive behavioral analysis and quantification of brain free amino acids of C57BL/6J congenic mice carrying the 1473G allele in tryptophan hydroxylase-2

AU - Koshimizu, Hisatsugu

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AU - Takao, Keizo

AU - Toyama, Keiko

AU - Ichinose, Takashi

AU - Furuya, Shigeki

AU - Miyakawa, Tsuyoshi

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N2 - Aim: Tryptophan hydroxylase 2 (Tph2) is a rate-limiting enzyme for the biosynthesis of 5-hydroxytryptamine (5-HT, serotonin). Previous studies have reported that C1473G polymorphism of the murine Tph2 gene leads to decreased 5-HT levels in the brain and abnormal behavioral phenotypes, such as impaired anxiety- and depression-like behaviors. In this study, to confirm the effect of the C1473G polymorphism on mouse phenotypes, we conducted a comprehensive battery of behavioral tests and measured the amounts of brain free amino acids involved in the production of 5-HT. Methods: We obtained C57BL/6J congenic mice that were homozygous for the 1473G allele of Tph2 (1473G) and subjected them and their wild-type littermates (1473C) to a battery of behavioral tests. Using reverse-phase high-performance liquid chromatography (HPLC), we measured the amounts of free amino acids in the 5-HT and epinephrine synthetic/metabolic pathways in the frontal cortex, hippocampus, striatum, and midbrain. Results: We failed to detect significant differences between genotypes in depression-like behaviors, anxiety-like behaviors, social behaviors, sensorimotor gaiting, or learning and memory, while 1473G mice exhibited a nominally significant impairment in gait analysis, which failed to reach study-wide significance. In the HPLC analysis, there were no significant differences in the amounts of 5-HT, dopamine, norepinephrine, and epinephrine in the frontal cortex, hippocampus, striatum, and midbrain. Conclusion: Our findings do not support the idea that congenic C57BL/6J mice carrying the 1473G allele may represent an animal model of mood disorder under normal conditions without stress.

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