PMID- 38037233
OWN - NLM
STAT- MEDLINE
DCOM- 20240304
LR  - 20240304
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Linking)
VI  - 291
IP  - 5
DP  - 2024 Mar
TI  - Indoleamine 2,3-dioxygenase 2 deficiency associates with autism-like behavior via 
      dopaminergic neuronal dysfunction.
PG  - 945-964
LID - 10.1111/febs.17019 [doi]
AB  - Indoleamine 2,3-dioxygenase 2 (IDO2) is an enzyme of the tryptophan-kynurenine 
      pathway that is constitutively expressed in the brain. To provide insight into 
      the physiological role of IDO2 in the brain, behavioral and neurochemical 
      analyses in IDO2 knockout (KO) mice were performed. IDO2 KO mice showed 
      stereotyped behavior, restricted interest and social deficits, traits that are 
      associated with behavioral endophenotypes of autism spectrum disorder (ASD). IDO2 
      was colocalized immunohistochemically with tyrosine-hydroxylase-positive cells in 
      dopaminergic neurons. In the striatum and amygdala of IDO2 KO mice, decreased 
      dopamine turnover was associated with increased alpha-synuclein level. 
      Correspondingly, levels of downstream dopamine D1 receptor signaling molecules 
      such as brain-derived neurotrophic factor and c-Fos positive proteins were 
      decreased. Furthermore, decreased abundance of ramified-type microglia resulted 
      in increased dendritic spine density in the striatum of IDO2 KO mice. Both 
      chemogenetic activation of dopaminergic neurons and treatment with 
      methylphenidate, a dopamine reuptake inhibitor, ameliorated the ASD-like behavior 
      of IDO2 KO mice. Sequencing analysis of exon regions in IDO2 from 309 ASD samples 
      identified a rare canonical splice site variant in one ASD case. These results 
      suggest that the IDO2 gene is, at least in part, a factor closely related to the 
      development of psychiatric disorders.
CI  - (c) 2023 Federation of European Biochemical Societies.
FAU - Ishikawa, Masaki
AU  - Ishikawa M
AD  - Department of Advanced Diagnostic System Development, Fujita Health University 
      Graduate School of Health Sciences, Toyoake, Japan.
FAU - Yamamoto, Yasuko
AU  - Yamamoto Y
AUID- ORCID: 0000-0001-8825-9188
AD  - Department of Advanced Diagnostic System Development, Fujita Health University 
      Graduate School of Health Sciences, Toyoake, Japan.
FAU - Wulaer, Bolati
AU  - Wulaer B
AUID- ORCID: 0000-0002-0864-9870
AD  - Department of Advanced Diagnostic System Development, Fujita Health University 
      Graduate School of Health Sciences, Toyoake, Japan.
AD  - Laboratory of Health and Medical Science Innovation, Fujita Health University 
      Graduate School of Health Science, Toyoake, Japan.
FAU - Kunisawa, Kazuo
AU  - Kunisawa K
AD  - Department of Regulatory Science for Evaluation & Development of Pharmaceuticals 
      & Devices, Fujita Health University Graduate School of Health Sciences, Toyoake, 
      Japan.
FAU - Fujigaki, Hidetsugu
AU  - Fujigaki H
AD  - Department of Advanced Diagnostic System Development, Fujita Health University 
      Graduate School of Health Sciences, Toyoake, Japan.
FAU - Ando, Tatsuya
AU  - Ando T
AD  - Department of Advanced Diagnostic System Development, Fujita Health University 
      Graduate School of Health Sciences, Toyoake, Japan.
FAU - Kimura, Hiroki
AU  - Kimura H
AD  - Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
FAU - Kushima, Itaru
AU  - Kushima I
AD  - Medical Genomics Center, Nagoya University Hospital, Nagoya, Japan.
FAU - Arioka, Yuko
AU  - Arioka Y
AD  - Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
FAU - Torii, Youta
AU  - Torii Y
AD  - Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
FAU - Mouri, Akihiro
AU  - Mouri A
AD  - Department of Regulatory Science for Evaluation & Development of Pharmaceuticals 
      & Devices, Fujita Health University Graduate School of Health Sciences, Toyoake, 
      Japan.
AD  - Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.
FAU - Ozaki, Norio
AU  - Ozaki N
AD  - Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
FAU - Nabeshima, Toshitaka
AU  - Nabeshima T
AD  - Laboratory of Health and Medical Science Innovation, Fujita Health University 
      Graduate School of Health Science, Toyoake, Japan.
AD  - Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.
FAU - Saito, Kuniaki
AU  - Saito K
AD  - Department of Advanced Diagnostic System Development, Fujita Health University 
      Graduate School of Health Sciences, Toyoake, Japan.
AD  - Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.
LA  - eng
GR  - 19K07490/Japan Society for the Promotion of Science/
GR  - 18K19761/Japan Society for the Promotion of Science/
GR  - 17H04252/Japan Society for the Promotion of Science/
GR  - Smoking Research Foundation/
PT  - Journal Article
DEP - 20240102
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - VTD58H1Z2X (Dopamine)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (IDO2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - *Autism Spectrum Disorder/genetics
MH  - *Autistic Disorder
MH  - Dopamine
MH  - Dopaminergic Neurons
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics
OTO - NOTNLM
OT  - autism spectrum disorder
OT  - brain-derived neurotropic factor
OT  - dopamine
OT  - endophenotypes
OT  - tryptophan-kynurenine pathway
EDAT- 2023/12/01 06:44
MHDA- 2024/03/04 06:47
CRDT- 2023/12/01 00:17
PHST- 2023/10/05 00:00 [revised]
PHST- 2023/04/19 00:00 [received]
PHST- 2023/11/29 00:00 [accepted]
PHST- 2024/03/04 06:47 [medline]
PHST- 2023/12/01 06:44 [pubmed]
PHST- 2023/12/01 00:17 [entrez]
AID - 10.1111/febs.17019 [doi]
PST - ppublish
SO  - FEBS J. 2024 Mar;291(5):945-964. doi: 10.1111/febs.17019. Epub 2024 Jan 2.