Dataset Information

Comprehensive behavioral analysis of indoleamine 2,3-dioxygenase knockout mice.

ABSTRACT: Aim: Indoleamine 2,3-dioxygenase 1 (IDO1) metabolizes the essential amino acid tryptophan into kynurenine derivatives, which are involved in neural activity via the kynurenine pathway (KP). IDO1 is an initial rate-limiting enzyme in the KP and is activated by stress and/or inflammation. The perturbation of IDO1 activity, which causes KP imbalance, is associated with psychiatric and neurological disorders. It has been reported that wild-type (WT) mice under inflammatory conditions show increased anxiety-like behavior and decreased novel object recognition, whereas Ido1 knockout (KO) mice do not display these behaviors. However, the behavioral phenotypes of Ido1 KO mice have not yet been fully examined under non-inflammatory conditions.

Methods: We subjected Ido1 KO mice to a comprehensive behavioral test battery under normal conditions.

Results: Ido1 KO mice and WT mice showed similar locomotor activity, anxiety-like behavior, social behavior, depression-like behavior, and fear memory. In the T-maze test, Ido1 KO mice exhibited weak but nominally significant impairment in the working memory task of the T-maze, but this result failed to reach study-wide significance.

Conclusions: Ido1 KO mice did not show any clear behavioral abnormalities under normal conditions. Further studies may be necessary to investigate their behavioral phenotype under inflammatory conditions due to their known roles in inflammation.

SUBMITTER: Hirata N

PROVIDER: S-EPMC7292290 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Comprehensive behavioral analysis of indoleamine 2,3-dioxygenase knockout mice.

Hirata Nao N Hattori Satoko S Shoji Hirotaka H Funakoshi Hiroshi H Miyakawa Tsuyoshi T

Neuropsychopharmacology reports 20180811 3

<h4>Aim</h4>Indoleamine 2,3-dioxygenase 1 (IDO1) metabolizes the essential amino acid tryptophan into kynurenine derivatives, which are involved in neural activity via the kynurenine pathway (KP). IDO1 is an initial rate-limiting enzyme in the KP and is activated by stress and/or inflammation. The perturbation of IDO1 activity, which causes KP imbalance, is associated with psychiatric and neurological disorders. It has been reported that wild-type (WT) mice under inflammatory conditions show inc ...[more]

PMID: 30175526

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Project description:AimsSynaptic Ras GTPase-activating protein 1 (SYNGAP1) regulates synaptic plasticity through AMPA receptor trafficking. SYNGAP1 mutations have been found in human patients with intellectual disability (ID) and autism spectrum disorder (ASD). Almost every individual with SYNGAP1-related ID develops epilepsy, and approximately 50% have ASD. SYNGAP1-related ID is estimated to account for at least 1% of ID cases. In mouse models with Syngap1 mutations, strong cognitive and affective dysfunctions have been reported, yet some findings are inconsistent across studies. To further understand the behavioral significance of the SYNGAP1 gene, we assessed various domains of behavior in Syngap1 heterozygous mutant mice using a behavioral test battery.MethodsMale mice with a heterozygous mutation in the Syngap1 gene (Syngap1-/+ mice) created by Seth Grant's group were subjected to a battery of comprehensive behavioral tests, which examined general health, and neurological screens, rotarod, hot plate, open field, light/dark transition, elevated plus maze, social interaction, prepulse inhibition, Porsolt forced swim, tail suspension, gait analysis, T-maze, Y-maze, Barnes maze, contextual and cued fear conditioning, and home cage locomotor activity. To control for type I errors due to multiple-hypothesis testing, P-values below the false discovery rate calculated by the Benjamini-Hochberg method were considered as study-wide statistically significant.ResultsSyngap1-/+ mice showed increased locomotor activity, decreased prepulse inhibition, and impaired working and reference spatial memory, consistent with preceding studies. Impairment of context fear memory and increased startle reflex in Syngap1 mutant mice could not be reproduced. Significant decreases in sensitivity to painful stimuli and impaired motor function were observed in Syngap1-/+ mice. Decreased anxiety-like behavior and depression-like behavior were noted, although increased locomotor activity is a potential confounding factor of these phenotypes. Increased home cage locomotor activity indicated hyperlocomotor activity not only in specific behavioral test conditions but also in familiar environments.ConclusionIn Syngap1-/+ mice, we could reproduce most of the previously reported cognitive and emotional deficits. The decreased sensitivity to painful stimuli and impaired motor function that we found in Syngap1-/+ mice are consistent with the common characteristics of patients with SYNGAP-related ID. We further confirmed that the Syngap1 heterozygote mouse recapitulates the symptoms of ID and ASD patients.

Dataset Information

Comprehensive behavioral analysis of indoleamine 2,3-dioxygenase knockout mice.

Publications

Comprehensive behavioral analysis of indoleamine 2,3-dioxygenase knockout mice.

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