PMID- 30003515
OWN - NLM
STAT- MEDLINE
DCOM- 20190717
LR  - 20200225
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 56
IP  - 3
DP  - 2019 Mar
TI  - Absence of Stress Response in Dorsal Raphe Nucleus in Modulator of Apoptosis 
      1-Deficient Mice.
PG  - 2185-2201
LID - 10.1007/s12035-018-1205-7 [doi]
AB  - Modulator of apoptosis 1 (MOAP-1) is a Bcl-2-associated X Protein 
      (BAX)-associating protein that plays an important role in regulating apoptosis. 
      It is highly enriched in the brain but its function in this organ remains 
      unknown. Studies on BAX(-/-) mice suggested that disruption of programmed cell 
      death may lead to abnormal emotional states. We thus hypothesize that MOAP-1(-/-) 
      mice may also display stress-related behavioral differences and perhaps involved 
      in stress responses in the brain and investigated if a depression-like trait 
      exists in MOAP-1(-/-) mice, and if so, whether it is age related, and how it 
      relates to central serotonergic stress response in the dorsal raphe nucleus. 
      Young MOAP-1(-/-) mice exhibit depression-like behavior, in the form of increased 
      immobility time when compared to age-matched wild-type mice in the forced 
      swimming test, which is abolished by acute treatment of fluoxetine. This is 
      supported by data from the tail suspension and sucrose preference tests. Repeated 
      forced swimming stress causes an up-regulation of tryptophan hydroxylase 2 (TPH2) 
      and a down-regulation of brain-derived neurotrophic factor (BDNF) in the dorsal 
      raphe nucleus (DRN) in young wild-type (WT) control mice. In contrast, TPH2 
      up-regulation was not observed in aged WT mice. Interestingly, such a stress 
      response appears absent in both young and aged MOAP-1(-/-) mice. Aged MOAP-1(-/-) 
      and WT mice also have similar immobility times on the forced swimming test. These 
      data suggest that MOAP-1 is required in the regulation of stress response in the 
      DRN. Crosstalk between BDNF and 5-HT appears to play an important role in this 
      stress response.
FAU - Zhao, Hui
AU  - Zhao H
AD  - Department of Pharmacology, Yong Loo Lin School of Medicine, National University 
      of Singapore, 16, Medical Drive, #04-01, Singapore, 117600, Singapore.
FAU - Mohamed, Nur-Ezan
AU  - Mohamed NE
AD  - Department of Pharmacology, Yong Loo Lin School of Medicine, National University 
      of Singapore, 16, Medical Drive, #04-01, Singapore, 117600, Singapore.
FAU - Chan, Su Jing
AU  - Chan SJ
AD  - Department of Pharmacology, Yong Loo Lin School of Medicine, National University 
      of Singapore, 16, Medical Drive, #04-01, Singapore, 117600, Singapore.
AD  - Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 
      Charlestown, MA, 02129, USA.
AD  - Institute of Medical Biology, Glycotherapeutics Group, 8A Biomedical Grove, 
      #06-06 Immunos, A*STAR, Singapore, 138648, Singapore.
FAU - Tan, Chong Teik
AU  - Tan CT
AD  - Department of Pharmacy, Faculty of Science, National University of Singapore, 
      Singapore, Singapore.
FAU - Tao, Ran
AU  - Tao R
AD  - Department of Pharmacy, Faculty of Science, National University of Singapore, 
      Singapore, Singapore.
FAU - Yu, Victor C
AU  - Yu VC
AD  - Department of Pharmacy, Faculty of Science, National University of Singapore, 
      Singapore, Singapore.
FAU - Wong, Peter T-H
AU  - Wong PT
AUID- ORCID: 0000-0002-6547-9353
AD  - Department of Pharmacology, Yong Loo Lin School of Medicine, National University 
      of Singapore, 16, Medical Drive, #04-01, Singapore, 117600, Singapore. 
      phcwth@nus.edu.sg.
LA  - eng
GR  - MOE2012-T2-1-132/Minstry of Education, Singapore/
PT  - Journal Article
DEP - 20180712
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Moap1 protein, mouse)
RN  - EC 1.14.16.4 (Tph2 protein, mouse)
RN  - EC 1.14.16.4 (Tryptophan Hydroxylase)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/genetics/*metabolism
MH  - Animals
MH  - Apoptosis Regulatory Proteins/genetics/*metabolism
MH  - Behavior, Animal/physiology
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Depression/genetics/metabolism
MH  - Dorsal Raphe Nucleus/*metabolism
MH  - Down-Regulation
MH  - Mice
MH  - Mice, Knockout
MH  - Stress, Physiological/*physiology
MH  - Stress, Psychological/genetics/*metabolism
MH  - Swimming
MH  - Tryptophan Hydroxylase/genetics/*metabolism
MH  - Up-Regulation
PMC - PMC6394635
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor
OT  - Depression
OT  - Dorsal raphe nucleus
OT  - Modulator of apoptosis
OT  - Serotonin
OT  - Stress
COIS- All procedures performed were approved by the Institutional Animal Care and Use 
      Committee (IACUC) at the National University of Singapore. CONFLICT OF INTEREST: 
      The authors declare that they have no conflict of interest.
EDAT- 2018/07/14 06:00
MHDA- 2019/07/18 06:00
PMCR- 2018/07/12
CRDT- 2018/07/14 06:00
PHST- 2017/10/01 00:00 [received]
PHST- 2018/06/26 00:00 [accepted]
PHST- 2018/07/14 06:00 [pubmed]
PHST- 2019/07/18 06:00 [medline]
PHST- 2018/07/14 06:00 [entrez]
PHST- 2018/07/12 00:00 [pmc-release]
AID - 10.1007/s12035-018-1205-7 [pii]
AID - 1205 [pii]
AID - 10.1007/s12035-018-1205-7 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2019 Mar;56(3):2185-2201. doi: 10.1007/s12035-018-1205-7. Epub 
      2018 Jul 12.