PMID- 34708129
OWN - NLM
STAT- MEDLINE
DCOM- 20220124
LR  - 20220124
IS  - 2314-6141 (Electronic)
IS  - 2314-6133 (Print)
VI  - 2021
DP  - 2021
TI  - Exploring Molecular Mechanisms Involved in the Development of the Depression-Like 
      Phenotype in Interleukin-18-Deficient Mice.
PG  - 9975865
LID - 10.1155/2021/9975865 [doi]
LID - 9975865
AB  - Interleukin-18 (IL-18) is an inflammatory cytokine that has been linked to energy 
      homeostasis and psychiatric symptoms such as depression and cognitive impairment. 
      We previously revealed that deficiency in IL-18 led to hippocampal abnormalities 
      and resulted in depression-like symptoms. However, the impact of IL-18 deficiency 
      on other brain regions remains to be clarified. In this study, we first sought to 
      confirm that IL-18 expression in neural cells can be found in human brain tissue. 
      Subsequently, we examined the expression of genes in the prefrontal cortex of 
      Il18 (-/-) mice and compared it with gene expression in mice subjected to a 
      chronic mild stress model of depression. Extracted genes were further analyzed 
      using Ingenuity(R) Pathway Analysis, in which 18 genes common to both the chronic 
      mild stressed model and Il18 (-/-) mice were identified. Of those, 16 were 
      significantly differentially expressed between Il18(+/+) and Il18 (-/-) mice. We 
      additionally measured protein expression of alpha-2-HS-glycoprotein (AHSG) and 
      transthyretin (TTR) in serum and the brain. In the prefrontal cortex of Il18 
      (-/-) mice, TTR but not AHSG was significantly decreased. Conversely, in the 
      serum of Il18 (-/-) mice, AHSG was significantly increased but not TTR. 
      Therefore, our results suggest that in IL-18-deficit conditions, TTR in the brain 
      is one of the mediators causally related to depression, and AHSG in peripheral 
      organs is one of the regulators inducing energy imbalance. Moreover, this study 
      suggests a possible "signpost" to clarify the molecular mechanisms commonly 
      underlying the immune system, energy metabolism, neural function, and depressive 
      disorders.
CI  - Copyright (c) 2021 Kyosuke Yamanishi et al.
FAU - Yamanishi, Kyosuke
AU  - Yamanishi K
AUID- ORCID: 0000-0001-5130-8193
AD  - Department of Psychoimmunology, Hyogo College of Medicine, Nishinomiya, Hyogo 
      663-8501, Japan.
AD  - Department of Neuropsychiatry, Hyogo College of Medicine, Nishinomiya, Hyogo 
      663-8501, Japan.
FAU - Miyauchi, Masahiro
AU  - Miyauchi M
AD  - Department of Neuropsychiatry, Hyogo College of Medicine, Nishinomiya, Hyogo 
      663-8501, Japan.
FAU - Mukai, Keiichiro
AU  - Mukai K
AD  - Department of Neuropsychiatry, Hyogo College of Medicine, Nishinomiya, Hyogo 
      663-8501, Japan.
FAU - Hashimoto, Takuya
AU  - Hashimoto T
AD  - Department of Neuropsychiatry, Hyogo College of Medicine, Nishinomiya, Hyogo 
      663-8501, Japan.
FAU - Uwa, Noriko
AU  - Uwa N
AD  - Department of Neuropsychiatry, Hyogo College of Medicine, Nishinomiya, Hyogo 
      663-8501, Japan.
FAU - Seino, Hitomi
AU  - Seino H
AD  - Department of Neuropsychiatry, Hyogo College of Medicine, Nishinomiya, Hyogo 
      663-8501, Japan.
FAU - Li, Wen
AU  - Li W
AD  - Department of Psychoimmunology, Hyogo College of Medicine, Nishinomiya, Hyogo 
      663-8501, Japan.
FAU - Gamachi, Naomi
AU  - Gamachi N
AD  - Department of Psychoimmunology, Hyogo College of Medicine, Nishinomiya, Hyogo 
      663-8501, Japan.
FAU - Hata, Masaki
AU  - Hata M
AD  - Department of Psychoimmunology, Hyogo College of Medicine, Nishinomiya, Hyogo 
      663-8501, Japan.
FAU - Kuwahara-Otani, Sachi
AU  - Kuwahara-Otani S
AD  - Department of Anatomy and Cell Biology, Hyogo College of Medicine, Nishinomiya, 
      Hyogo 663-8501, Japan.
AD  - General Education Center, Hyogo University of Health Sciences, Chuo-ku, Kobe, 
      Hyogo 650-8530, Japan.
FAU - Maeda, Seishi
AU  - Maeda S
AD  - Department of Anatomy and Cell Biology, Hyogo College of Medicine, Nishinomiya, 
      Hyogo 663-8501, Japan.
FAU - Watanabe, Yuko
AU  - Watanabe Y
AUID- ORCID: 0000-0003-3706-5978
AD  - Hirakata General Hospital for Developmental Disorders, 2-1-1, Tsudahigashi, 
      Hirakata, Osaka 573-0122, Japan.
FAU - Yamanishi, Hiromichi
AU  - Yamanishi H
AD  - Hirakata General Hospital for Developmental Disorders, 2-1-1, Tsudahigashi, 
      Hirakata, Osaka 573-0122, Japan.
FAU - Yagi, Hideshi
AU  - Yagi H
AD  - Department of Anatomy and Cell Biology, Hyogo College of Medicine, Nishinomiya, 
      Hyogo 663-8501, Japan.
FAU - Okamura, Haruki
AU  - Okamura H
AD  - Department of Psychoimmunology, Hyogo College of Medicine, Nishinomiya, Hyogo 
      663-8501, Japan.
FAU - Matsunaga, Hisato
AU  - Matsunaga H
AUID- ORCID: 0000-0002-3724-3722
AD  - Department of Psychoimmunology, Hyogo College of Medicine, Nishinomiya, Hyogo 
      663-8501, Japan.
AD  - Department of Neuropsychiatry, Hyogo College of Medicine, Nishinomiya, Hyogo 
      663-8501, Japan.
LA  - eng
PT  - Journal Article
DEP - 20211018
PL  - United States
TA  - Biomed Res Int
JT  - BioMed research international
JID - 101600173
RN  - 0 (IL18 protein, human)
RN  - 0 (Interleukin-18)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Brain/metabolism
MH  - Depression/immunology
MH  - Depressive Disorder/*immunology
MH  - Disease Models, Animal
MH  - Humans
MH  - Interleukin-18/*deficiency/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurons/metabolism
MH  - Prefrontal Cortex/metabolism
PMC - PMC8545524
COIS- All authors have read the journal's policy on the disclosure of potential 
      conflicts of interest and have none to declare.
EDAT- 2021/10/29 06:00
MHDA- 2022/01/27 06:00
PMCR- 2021/10/18
CRDT- 2021/10/28 06:43
PHST- 2021/03/16 00:00 [received]
PHST- 2021/09/18 00:00 [accepted]
PHST- 2021/10/28 06:43 [entrez]
PHST- 2021/10/29 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/10/18 00:00 [pmc-release]
AID - 10.1155/2021/9975865 [doi]
PST - epublish
SO  - Biomed Res Int. 2021 Oct 18;2021:9975865. doi: 10.1155/2021/9975865. eCollection 
      2021.