PMID- 27215202
OWN - NLM
STAT- MEDLINE
DCOM- 20180309
LR  - 20211204
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 54
IP  - 5
DP  - 2017 Jul
TI  - Progranulin Protects Hippocampal Neurogenesis via Suppression of 
      Neuroinflammatory Responses Under Acute Immune Stress.
PG  - 3717-3728
LID - 10.1007/s12035-016-9939-6 [doi]
AB  - Immune stress is well known to suppress adult neurogenesis in the hippocampus. We 
      have demonstrated that progranulin (PGRN) has a mitogenic effect on neurogenesis 
      under several experimental conditions. We have also shown that PGRN suppresses 
      excessive neuroinflammatory responses after traumatic brain injury. However, the 
      role of PGRN in modulating neurogenesis under acute immune stress is yet to be 
      elucidated. In the present study, we evaluated the involvement of PGRN in 
      neurogenesis and inflammatory responses in the hippocampus using a 
      lipopolysaccharide (LPS)-induced immune stress model. Treatment of mice with LPS 
      significantly increased the expression of PGRN in activated microglia and 
      decreased neurogenesis in the dentate gyrus of the hippocampus. PGRN deficiency 
      increased CD68-immunoreactive area and exacerbated suppression of neurogenesis 
      following LPS treatment. The expression levels of lysosomal genes including 
      lysozyme M, macrophage expressed gene 1, and cathepsin Z were higher in 
      PGRN-deficient than in wild-type mice, while PGRN deficiency decreased mammalian 
      target of rapamycin (mTOR) mRNA levels, suggesting that PGRN suppresses excessive 
      lysosomal biogenesis by promoting mTOR signaling. LPS treatment also increased 
      the expression of proinflammatory genes such as interleukin (IL)-1beta, tumor 
      necrosis factor-alpha, and microsomal prostaglandin E synthase-1 (mPGES-1) in the 
      hippocampus, and PGRN deficiency further enhanced gene expression of IL-6 and 
      mPGES-1. These results suggest that PGRN plays a protecting role in hippocampal 
      neurogenesis at least partially by attenuating neuroinflammatory responses during 
      LPS-induced acute immune stress.
FAU - Ma, Yanbo
AU  - Ma Y
AD  - Department of Veterinary Physiology, Graduate School of Agricultural and Life 
      Sciences, The University of Tokyo, Tokyo, 113-8657, Japan.
FAU - Matsuwaki, Takashi
AU  - Matsuwaki T
AD  - Department of Veterinary Physiology, Graduate School of Agricultural and Life 
      Sciences, The University of Tokyo, Tokyo, 113-8657, Japan.
FAU - Yamanouchi, Keitaro
AU  - Yamanouchi K
AD  - Department of Veterinary Physiology, Graduate School of Agricultural and Life 
      Sciences, The University of Tokyo, Tokyo, 113-8657, Japan.
FAU - Nishihara, Masugi
AU  - Nishihara M
AD  - Department of Veterinary Physiology, Graduate School of Agricultural and Life 
      Sciences, The University of Tokyo, Tokyo, 113-8657, Japan. 
      amnishi@mail.ecc.u-tokyo.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20160523
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Granulins)
RN  - 0 (Grn protein, mouse)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Progranulins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Granulins
MH  - Hippocampus/metabolism/*pathology
MH  - Inflammation/genetics/*immunology/metabolism/pathology
MH  - Intercellular Signaling Peptides and Proteins/deficiency/metabolism
MH  - Lipopolysaccharides
MH  - Lysosomes/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Microglia/metabolism/pathology
MH  - *Neurogenesis
MH  - Progranulins
MH  - Signal Transduction
MH  - Stress, Physiological/*immunology
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - Immune stress
OT  - Microglia
OT  - Neurogenesis
OT  - Neuroinflammation
OT  - Progranulin
EDAT- 2016/05/25 06:00
MHDA- 2018/03/10 06:00
CRDT- 2016/05/25 06:00
PHST- 2016/02/24 00:00 [received]
PHST- 2016/05/10 00:00 [accepted]
PHST- 2016/05/25 06:00 [pubmed]
PHST- 2018/03/10 06:00 [medline]
PHST- 2016/05/25 06:00 [entrez]
AID - 10.1007/s12035-016-9939-6 [pii]
AID - 10.1007/s12035-016-9939-6 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2017 Jul;54(5):3717-3728. doi: 10.1007/s12035-016-9939-6. Epub 
      2016 May 23.