PMID- 29534628
OWN - NLM
STAT- MEDLINE
DCOM- 20191011
LR  - 20191011
IS  - 1461-7285 (Electronic)
IS  - 0269-8811 (Linking)
VI  - 32
IP  - 4
DP  - 2018 Apr
TI  - Gemfibrozil has antidepressant effects in mice: Involvement of the hippocampal 
      brain-derived neurotrophic factor system.
PG  - 469-481
LID - 10.1177/0269881118762072 [doi]
AB  - Major depressive disorder has become one of the most serious neuropsychiatric 
      disorders worldwide. However, currently available antidepressants used in 
      clinical practice are ineffective for a substantial proportion of patients and 
      always have side effects. Besides being a lipid-regulating agent, gemfibrozil is 
      an agonist of peroxisome proliferator-activated receptor-alpha (PPAR-alpha). We 
      investigated the antidepressant effects of gemfibrozil on C57BL/6J mice using the 
      forced swim test (FST) and tail suspension test (TST), as well as the chronic 
      unpredictable mild stress (CUMS) model of depression. The changes in 
      brain-derived neurotrophic factor (BDNF) signaling cascade in the brain after 
      CUMS and gemfibrozil treatment were further assessed. Pharmacological inhibitors 
      and lentivirus-expressed short hairpin RNA (shRNA) were also used to clarify the 
      antidepressant mechanisms of gemfibrozil. Gemfibrozil exhibited significant 
      antidepressant actions in the FST and TST without affecting the locomotor 
      activity of mice. Chronic gemfibrozil administration fully reversed CUMS-induced 
      depressive-like behaviors in the FST, TST and sucrose preference test. 
      Gemfibrozil treatment also restored CUMS-induced inhibition of the hippocampal 
      BDNF signaling pathway. Blocking PPAR-alpha and BDNF but not the serotonergic system 
      abolished the antidepressant effects of gemfibrozil on mice. Gemfibrozil produced 
      antidepressant effects in mice by promoting the hippocampal BDNF system.
FAU - Ni, Yu-Fei
AU  - Ni YF
AD  - 1 Nantong Maternal and Child Health Care Hospital, China.
FAU - Wang, Hao
AU  - Wang H
AD  - 2 Department of Pharmacology, School of Pharmacy, Nantong University, China.
FAU - Gu, Qiu-Yan
AU  - Gu QY
AD  - 1 Nantong Maternal and Child Health Care Hospital, China.
FAU - Wang, Fei-Ying
AU  - Wang FY
AD  - 1 Nantong Maternal and Child Health Care Hospital, China.
FAU - Wang, Ying-Jie
AU  - Wang YJ
AD  - 2 Department of Pharmacology, School of Pharmacy, Nantong University, China.
FAU - Wang, Jin-Liang
AU  - Wang JL
AD  - 2 Department of Pharmacology, School of Pharmacy, Nantong University, China.
FAU - Jiang, Bo
AU  - Jiang B
AD  - 2 Department of Pharmacology, School of Pharmacy, Nantong University, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180314
PL  - United States
TA  - J Psychopharmacol
JT  - Journal of psychopharmacology (Oxford, England)
JID - 8907828
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carbazoles)
RN  - 0 (Creb1 protein, mouse)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (GW 6471)
RN  - 0 (Indole Alkaloids)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Oxazoles)
RN  - 0 (RNA, Small Interfering)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 333DO1RDJY (Serotonin)
RN  - 42HK56048U (Tyrosine)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - EC 2.7.10.1 (Ntrk2 protein, mouse)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - Q8X02027X3 (Gemfibrozil)
RN  - R5J7E3L9SP (Fenclonine)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*pharmacology
MH  - Behavior, Animal/*drug effects
MH  - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/*metabolism
MH  - Carbazoles/pharmacology
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Fenclonine/pharmacology
MH  - Fluoxetine/pharmacology
MH  - Gemfibrozil/antagonists & inhibitors/*pharmacology
MH  - Hippocampus/*drug effects/*metabolism
MH  - Immobility Response, Tonic/drug effects
MH  - Indole Alkaloids/pharmacology
MH  - Male
MH  - Membrane Glycoproteins/antagonists & inhibitors/metabolism
MH  - Mice
MH  - Motor Activity/drug effects
MH  - Oxazoles/pharmacology
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism
MH  - RNA, Small Interfering/pharmacology
MH  - Serotonin/metabolism
MH  - Signal Transduction/*drug effects
MH  - Tyrosine/analogs & derivatives/pharmacology
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor
OT  - chronic unpredictable mild stress
OT  - depression
OT  - gemfibrozil
EDAT- 2018/03/15 06:00
MHDA- 2019/10/12 06:00
CRDT- 2018/03/15 06:00
PHST- 2018/03/15 06:00 [pubmed]
PHST- 2019/10/12 06:00 [medline]
PHST- 2018/03/15 06:00 [entrez]
AID - 10.1177/0269881118762072 [doi]
PST - ppublish
SO  - J Psychopharmacol. 2018 Apr;32(4):469-481. doi: 10.1177/0269881118762072. Epub 
      2018 Mar 14.