Comprehensive behavioral analysis of tryptophan 2,3-dioxygenase (Tdo2) knockout mice:

Satoko Takai, Keizo Takao, Hiroshi Funakoshi, Tsuyoshi Miyakawa

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Aims: Tryptophan 2,3-dioxygenase (TDO2) is an initial rate-limiting enzyme of the kynurenine (Kyn) pathway in tryptophan (Trp) metabolism. The Trp-degrading enzymes, TDO2 and indoleamine 2,3-dioxygenase, are activated by stress and/or inflammation. Dysregulation of Trp metabolism, which causes shifts in the balance between Kyn and serotonin (5-HT) pathways, is associated with psychiatric and neurological disorders. In genetic studies, single-nucleotide polymorphisms in the TDO2 gene were shown to be involved in psychiatric disorders, such as schizophrenia and depression. It has been reported that targeted deletion of the Tdo2 gene in mice resulted in reduced anxiety-like behavior, enhanced exploratory activity and cognitive performance, and increased levels of Trp and 5-HT in the hippocampus and midbrain. However, the effect of Tdo2 gene deletion on behavioral phenotypes has not yet been investigated extensively. Materials & Methods: We conducted tests to further examine the behavioral effects of knockout (KO) of Tdo2 in mice. Results: Deletion of Tdo2 resulted in seemingly lower anxiety-like behavior, higher locomotor activity, and abnormal gait pattern in mice, though none of them reached study-wide statistical significance. Tdo2 deficiency had no significant effects on other behaviors, such as prepulse inhibition, and depression-like and social behaviors. Discussion and Conclusion: He lack of clear phenotypes in Tdo2KO mice in this study might be due to the absence of stress and inflammatory conditions, which could induce expression of Tdo2 mRNA. Further studies are necessary to elucidate the roles of Tdo2 in behavioral phenotypes related to psychiatric disorders. It has been reported that TDO2 gene is involved in psychiatric disorders, such as schizophrenia and depression. However, the effect of Tdo2 gene deletion on behavioral phenotypes has not yet been investigated extensively. Here, we conducted tests to further examine the behavioral effects of knockout (KO) of Tdo2 in mice.

Original languageEnglish
Pages (from-to)52-60
Number of pages9
JournalNeuropsychopharmacology reports
Volume38
Issue number2
DOIs
Publication statusPublished - 01-06-2018

Fingerprint

Tryptophan Oxygenase
Knockout Mice
Tryptophan
Psychiatry
Gene Deletion
Kynurenine
Phenotype
Serotonin
Depression
Schizophrenia
Anxiety
Indoleamine-Pyrrole 2,3,-Dioxygenase
Exploratory Behavior
Social Behavior
Enzymes
Locomotion
Mesencephalon
Nervous System Diseases
Gait
Genes

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 of tryptophan 2,3-dioxygenase (Tdo2) knockout mice:",
abstract = "Aims: Tryptophan 2,3-dioxygenase (TDO2) is an initial rate-limiting enzyme of the kynurenine (Kyn) pathway in tryptophan (Trp) metabolism. The Trp-degrading enzymes, TDO2 and indoleamine 2,3-dioxygenase, are activated by stress and/or inflammation. Dysregulation of Trp metabolism, which causes shifts in the balance between Kyn and serotonin (5-HT) pathways, is associated with psychiatric and neurological disorders. In genetic studies, single-nucleotide polymorphisms in the TDO2 gene were shown to be involved in psychiatric disorders, such as schizophrenia and depression. It has been reported that targeted deletion of the Tdo2 gene in mice resulted in reduced anxiety-like behavior, enhanced exploratory activity and cognitive performance, and increased levels of Trp and 5-HT in the hippocampus and midbrain. However, the effect of Tdo2 gene deletion on behavioral phenotypes has not yet been investigated extensively. Materials & Methods: We conducted tests to further examine the behavioral effects of knockout (KO) of Tdo2 in mice. Results: Deletion of Tdo2 resulted in seemingly lower anxiety-like behavior, higher locomotor activity, and abnormal gait pattern in mice, though none of them reached study-wide statistical significance. Tdo2 deficiency had no significant effects on other behaviors, such as prepulse inhibition, and depression-like and social behaviors. Discussion and Conclusion: He lack of clear phenotypes in Tdo2KO mice in this study might be due to the absence of stress and inflammatory conditions, which could induce expression of Tdo2 mRNA. Further studies are necessary to elucidate the roles of Tdo2 in behavioral phenotypes related to psychiatric disorders. It has been reported that TDO2 gene is involved in psychiatric disorders, such as schizophrenia and depression. However, the effect of Tdo2 gene deletion on behavioral phenotypes has not yet been investigated extensively. Here, we conducted tests to further examine the behavioral effects of knockout (KO) of Tdo2 in mice.",
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Comprehensive behavioral analysis of tryptophan 2,3-dioxygenase (Tdo2) knockout mice: / Takai, Satoko; Takao, Keizo; Funakoshi, Hiroshi; Miyakawa, Tsuyoshi.

In: Neuropsychopharmacology reports, Vol. 38, No. 2, 01.06.2018, p. 52-60.

Research output: Contribution to journalArticle

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