PMID- 30981863
OWN - NLM
STAT- MEDLINE
DCOM- 20200109
LR  - 20200109
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 408
DP  - 2019 Jun 1
TI  - Interleukin-18-deficient mice develop hippocampal abnormalities related to 
      possible depressive-like behaviors.
PG  - 147-160
LID - S0306-4522(19)30241-6 [pii]
LID - 10.1016/j.neuroscience.2019.04.003 [doi]
AB  - Interleukin-18 (IL-18) is an inflammatory cytokine linked to major depressive 
      disorder (MDD). MDD is closely related to metabolic disorders, such as diabetes 
      mellitus (DM) and obesity. Moreover, DM is associated with cognitive impairment 
      and promotes apoptosis of hippocampal cells by activating pro-apoptotic and 
      inhibiting anti-apoptotic factors. IL-18-deficient (Il18(-/-)) mice are obese and 
      have DM. Therefore, we hypothesized a close relationship between IL-18 and death 
      of hippocampal cells, affecting neurogenesis related to behavioral changes such 
      as MDD. Il18(-/-) male mice were generated on the C57Bl/6 background and 
      Il18(+/+) mice were used as controls. Behavioral, histopathological, and 
      molecular responses, as well as responses to intracerebral recombinant IL-18 
      administration, were examined. Compared with Il18(+/+) mice, Il18(-/-) mice had 
      impaired learning and memory and exhibited lower motivation. In the Il18(-/-) 
      mice, degenerated mitochondria were detected in synaptic terminals in the 
      molecular layer, the polymorphic layer, and in mossy fibers in the dentate gyrus, 
      suggesting mitochondrial abnormalities. Because of the degeneration of 
      mitochondria in the dentate gyrus, in which pro-apoptotic molecules were 
      upregulated and anti-apoptotic factors were decreased, apoptosis inducers were 
      not cleaved, indicating inhibition of apoptosis. In addition, neurogenesis in the 
      dentate gyrus and the maturity of neuronal cells were decreased in the Il18(-/-) 
      mice, while intracerebral administration of recombinant IL-18 promoted 
      significant recovery of neurogenesis. Our findings suggested that IL-18 was 
      indispensable for mitochondrial homeostasis, sustaining clearance of degenerative 
      neural cells, and supporting neurogenesis, normal neuronal maturation and 
      hippocampal function.
CI  - Copyright (c) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Yamanishi, Kyosuke
AU  - Yamanishi K
AD  - Department of Neuropsychiatry, Hyogo College of Medicine, 1-1, Mukogawa, 
      Nishinomiya, Hyogo 6638501, Japan.
FAU - Doe, Nobutaka
AU  - Doe N
AD  - Laboratory of Neurogenesis and CNS Repair, Hyogo College of Medicine, 1-1, 
      Mukogawa, Nishinomiya, Hyogo 6638501, Japan; Laboratory of Psychology, General 
      Education Center, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, 
      Kobe, Hyogo, 6508530, Japan.
FAU - Mukai, Keiichiro
AU  - Mukai K
AD  - Department of Neuropsychiatry, Hyogo College of Medicine, 1-1, Mukogawa, 
      Nishinomiya, Hyogo 6638501, Japan.
FAU - Ikubo, Kaoru
AU  - Ikubo K
AD  - Department of Neuropsychiatry, Hyogo College of Medicine, 1-1, Mukogawa, 
      Nishinomiya, Hyogo 6638501, Japan.
FAU - Hashimoto, Takuya
AU  - Hashimoto T
AD  - Department of Neuropsychiatry, Hyogo College of Medicine, 1-1, Mukogawa, 
      Nishinomiya, Hyogo 6638501, Japan.
FAU - Uwa, Noriko
AU  - Uwa N
AD  - Department of Neuropsychiatry, Hyogo College of Medicine, 1-1, Mukogawa, 
      Nishinomiya, Hyogo 6638501, Japan.
FAU - Sumida, Miho
AU  - Sumida M
AD  - Laboratory of Psychology, General Education Center, Hyogo University of Health 
      Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo, 6508530, Japan.
FAU - El-Darawish, Yosif
AU  - El-Darawish Y
AD  - Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, 1-1, 
      Mukogawa, Nishinomiya, Hyogo, 6638501, Japan.
FAU - Gamachi, Naomi
AU  - Gamachi N
AD  - Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, 1-1, 
      Mukogawa, Nishinomiya, Hyogo, 6638501, Japan.
FAU - Li, Wen
AU  - Li W
AD  - Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, 1-1, 
      Mukogawa, Nishinomiya, Hyogo, 6638501, Japan.
FAU - Kuwahara-Otani, Sachi
AU  - Kuwahara-Otani S
AD  - Department of Anatomy and Cell Biology, Hyogo College of Medicine, 1-1, Mukogawa, 
      Nishinomiya, Hyogo, 6638501, Japan.
FAU - Maeda, Seishi
AU  - Maeda S
AD  - Department of Anatomy and Cell Biology, Hyogo College of Medicine, 1-1, Mukogawa, 
      Nishinomiya, Hyogo, 6638501, Japan.
FAU - Watanabe, Yuko
AU  - Watanabe Y
AD  - Hirakata General Hospital for Developmental Disorders, 2-1-1 Tsudahigashi, 
      Hirakata, Osaka 5730122, Japan.
FAU - Hayakawa, Tetsu
AU  - Hayakawa T
AD  - Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, 1-1, 
      Mukogawa, Nishinomiya, Hyogo, 6638501, Japan.
FAU - Yamanishi, Hiromichi
AU  - Yamanishi H
AD  - Hirakata General Hospital for Developmental Disorders, 2-1-1 Tsudahigashi, 
      Hirakata, Osaka 5730122, Japan.
FAU - Matsuyama, Tomohiro
AU  - Matsuyama T
AD  - Laboratory of Neurogenesis and CNS Repair, Hyogo College of Medicine, 1-1, 
      Mukogawa, Nishinomiya, Hyogo 6638501, Japan.
FAU - Yagi, Hideshi
AU  - Yagi H
AD  - Department of Anatomy and Cell Biology, Hyogo College of Medicine, 1-1, Mukogawa, 
      Nishinomiya, Hyogo, 6638501, Japan.
FAU - Okamura, Haruki
AU  - Okamura H
AD  - Laboratory of Tumor Immunology and Cell Therapy, Hyogo College of Medicine, 1-1, 
      Mukogawa, Nishinomiya, Hyogo, 6638501, Japan.
FAU - Matsunaga, Hisato
AU  - Matsunaga H
AD  - Department of Neuropsychiatry, Hyogo College of Medicine, 1-1, Mukogawa, 
      Nishinomiya, Hyogo 6638501, Japan. Electronic address: hisa1311@hyo-med.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190411
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Interleukin-18)
SB  - IM
MH  - Animals
MH  - Cell Death/drug effects/*physiology
MH  - Depression/genetics/*metabolism/pathology
MH  - Hippocampus/drug effects/metabolism/*pathology
MH  - Interleukin-18/genetics/*metabolism/pharmacology
MH  - Learning/drug effects/physiology
MH  - Memory/drug effects/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Motivation/drug effects/physiology
MH  - Neurogenesis/drug effects/physiology
MH  - Neurons/drug effects/*metabolism/pathology
OTO - NOTNLM
OT  - depression
OT  - hippocampus
OT  - interleukin-18
OT  - learning and memory
OT  - mitochondria
OT  - neurogenesis
EDAT- 2019/04/15 06:00
MHDA- 2020/01/10 06:00
CRDT- 2019/04/15 06:00
PHST- 2018/08/25 00:00 [received]
PHST- 2019/03/27 00:00 [revised]
PHST- 2019/04/02 00:00 [accepted]
PHST- 2019/04/15 06:00 [pubmed]
PHST- 2020/01/10 06:00 [medline]
PHST- 2019/04/15 06:00 [entrez]
AID - S0306-4522(19)30241-6 [pii]
AID - 10.1016/j.neuroscience.2019.04.003 [doi]
PST - ppublish
SO  - Neuroscience. 2019 Jun 1;408:147-160. doi: 10.1016/j.neuroscience.2019.04.003. 
      Epub 2019 Apr 11.