PMID- 30914305
OWN - NLM
STAT- MEDLINE
DCOM- 20200121
LR  - 20200121
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 150
DP  - 2019 May 15
TI  - Mechanisms underpinning AMP-activated protein kinase-related effects on behavior 
      and hippocampal neurogenesis in an animal model of depression.
PG  - 121-133
LID - S0028-3908(19)30105-4 [pii]
LID - 10.1016/j.neuropharm.2019.03.026 [doi]
AB  - Adenosine monophosphate-activated protein kinase (AMPK) is critical for 
      whole-body energy metabolism regulation. Recent studies have suggested that 
      physical exercise ameliorates depressive-like behaviors via AMPK activation; 
      however, the underlying mechanism is unclear. Here, we examined the effects and 
      underlying mechanisms of AMPK activation on depressive-like behavior in olfactory 
      bulbectomized (OBX) mice. We treated OBX mice with the AMPK activator, 
      5-aminoimidazole-4-carboxamide-1-beta-d-ribonucleotide (AICAR) on the 7th or 14th 
      day after bilateral bulbectomy and evaluated depressive-like behavior using the 
      tail-suspension test (TST) and forced swimming test (FST) on the 21st day. The 
      expression of phosphorylated AMPK, protein kinase C zeta (PKCzeta), nuclear 
      factor-kappa B (NF-kappaB), brain-derived neurotrophic factor (BDNF), and cAMP 
      response element-binding protein (CREB) in the hippocampus was assessed by 
      western blotting. Hippocampal neurogenesis and localization of AMPK and 
      phosphorylated NF-kappaB were examined by immunohistochemistry. Chronic AICAR 
      treatment suppressed the prolonged immobility of OBX mice in the TST and FST, and 
      increased the levels of phosphorylated AMPK, PKCzeta, NF-kappaB, CREB, and BDNF. 
      Hippocampal neurogenesis in OBX mice was promoted by chronic AICAR treatment. 
      Co-administration of AICAR with the PKCzeta inhibitor or the neurotrophic tyrosine 
      kinase receptor type 2 (TrkB) antagonist, ANA-12, inhibited these effects. 
      Phosphorylated AMPK was detected in mature and immature hippocampal neurons and 
      microglia, while phosphorylated NF-kappaB was detected only in neurons in 
      AICAR-treated OBX mice. These data indicate that AMPK activation produces 
      anti-depressant effects, which are mediated by elevated hippocampal neurogenesis 
      potentially via PKCzeta/NF-kappaB/BDNF/TrkB/CREB signaling in neurons.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Odaira, Takayo
AU  - Odaira T
AD  - Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical 
      and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, 
      Japan.
FAU - Nakagawasai, Osamu
AU  - Nakagawasai O
AD  - Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical 
      and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, 
      Japan. Electronic address: osamun@tohoku-mpu.ac.jp.
FAU - Takahashi, Kohei
AU  - Takahashi K
AD  - Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical 
      and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, 
      Japan.
FAU - Nemoto, Wataru
AU  - Nemoto W
AD  - Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical 
      and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, 
      Japan.
FAU - Sakuma, Wakana
AU  - Sakuma W
AD  - Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical 
      and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, 
      Japan.
FAU - Lin, Jia-Rong
AU  - Lin JR
AD  - Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical 
      and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, 
      Japan.
FAU - Tan-No, Koichi
AU  - Tan-No K
AD  - Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical 
      and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190323
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (NF-kappa B)
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
SB  - IM
MH  - AMP-Activated Protein Kinases/*antagonists & inhibitors/metabolism
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/pharmacology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Depression/*metabolism
MH  - Disease Models, Animal
MH  - Hindlimb Suspension
MH  - Hippocampus/*drug effects/metabolism
MH  - Male
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Neurogenesis/*drug effects
MH  - Phosphorylation/drug effects
MH  - Ribonucleotides/*pharmacology
MH  - Signal Transduction/drug effects
EDAT- 2019/03/28 06:00
MHDA- 2020/01/22 06:00
CRDT- 2019/03/28 06:00
PHST- 2018/10/16 00:00 [received]
PHST- 2019/03/01 00:00 [revised]
PHST- 2019/03/19 00:00 [accepted]
PHST- 2019/03/28 06:00 [pubmed]
PHST- 2020/01/22 06:00 [medline]
PHST- 2019/03/28 06:00 [entrez]
AID - S0028-3908(19)30105-4 [pii]
AID - 10.1016/j.neuropharm.2019.03.026 [doi]
PST - ppublish
SO  - Neuropharmacology. 2019 May 15;150:121-133. doi: 
      10.1016/j.neuropharm.2019.03.026. Epub 2019 Mar 23.