PMID- 29374533
OWN - NLM
STAT- MEDLINE
DCOM- 20190523
LR  - 20210109
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 119
DP  - 2018 May 1
TI  - Circadian control of p75 neurotrophin receptor leads to alternate activation of 
      Nrf2 and c-Rel to reset energy metabolism in astrocytes via brain-derived 
      neurotrophic factor.
PG  - 34-44
LID - S0891-5849(18)30036-4 [pii]
LID - 10.1016/j.freeradbiomed.2018.01.026 [doi]
AB  - Circadian clock genes regulate energy metabolism partly through neurotrophins in 
      the body. The low affinity neurotrophin receptor p75(NTR) is a clock component 
      directly regulated by the transcriptional factor Clock:Bmal1 complex. 
      Brain-derived neurotrophic factor (BDNF) is expressed in the brain and plays a 
      key role in coordinating metabolic interactions between neurons and astrocytes. 
      BDNF transduces signals through TrkB and p75(NTR) receptors. This review 
      highlights a novel molecular mechanism by which BDNF via circadian control of 
      p75(NTR) leads to daily resetting of glucose and glycogen metabolism in brain 
      astrocytes to accommodate their functional interaction with neurons. Astrocytes 
      store glycogen as an energy reservoir to provide active neurons with the 
      glycolytic metabolite lactate. Astrocytes predominantly express the truncated 
      receptor TrkB.T1 which lacks an intracellular receptor tyrosine kinase domain. 
      TrkB.T1 retains the capacity to regulate cell morphology through regulation of 
      Rho GTPases. In contrast, p75(NTR) mediates generation of the bioactive lipid 
      ceramide upon stimulation with BDNF and inhibits PKA activation. As ceramide 
      directly activates PKCzeta, we discuss the importance of the 
      TrkB.T1-p75(NTR)-ceramide-PKCzeta signaling axis in the stimulation of glycogen and 
      lipid synthesis and activation of RhoA. Ceramide-PKCzeta-casein kinase 2 signaling 
      activates Nrf2 to support oxidative phosphorylation via upregulation of 
      antioxidant enzymes. In the absence of p75(NTR), TrkB.T1 functionally interacts 
      with adenosine A(2A)R and dopamine D1R receptors to enhance cAMP-PKA signaling 
      and activate Rac1 and NF-kappaB c-Rel, favoring glycogen hydrolysis, gluconeogenesis 
      and aerobic glycolysis. Thus, diurnal changes in p75(NTR) levels in astrocytes 
      resets energy metabolism via BDNF to accommodate their metabolic interaction with 
      neurons.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Ishii, Tetsuro
AU  - Ishii T
AD  - School of Medicine, University of Tsukuba, Tsukuba Ibaraki 305-0863, Japan. 
      Electronic address: ishiitetsuro305@gmail.com.
FAU - Warabi, Eiji
AU  - Warabi E
AD  - School of Medicine, University of Tsukuba, Tsukuba Ibaraki 305-0863, Japan.
FAU - Mann, Giovanni E
AU  - Mann GE
AD  - School of Cardiovascular Medicine and Sciences, King's British Heart Foundation 
      Centre of Excellence, Faculty of Life Sciences and Medicine, King's College 
      London, 150 Stamford Street, London SE1 9NH, UK.
LA  - eng
GR  - FS/15/6/31298/BHF_/British Heart Foundation/United Kingdom
GR  - FS/16/67/32548/BHF_/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20180131
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Proto-Oncogene Proteins c-rel)
RN  - 0 (Receptor, Nerve Growth Factor)
SB  - IM
MH  - Animals
MH  - Astrocytes/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Circadian Clocks/physiology
MH  - Circadian Rhythm/*physiology
MH  - Energy Metabolism/*physiology
MH  - Humans
MH  - NF-E2-Related Factor 2/metabolism
MH  - Proto-Oncogene Proteins c-rel/metabolism
MH  - Receptor, Nerve Growth Factor/*metabolism
MH  - Signal Transduction/physiology
OTO - NOTNLM
OT  - Astrocytes
OT  - Brain-derived neurotrophic factor
OT  - Circadian rhythm
OT  - Clock genes
OT  - Glycogen
OT  - Nrf2
OT  - Per2
OT  - Rac1
OT  - RhoA
OT  - Sequestosome-1
OT  - TrkB
OT  - c-Rel
OT  - p75(NTR)
EDAT- 2018/01/29 06:00
MHDA- 2019/05/24 06:00
CRDT- 2018/01/29 06:00
PHST- 2017/09/21 00:00 [received]
PHST- 2018/01/17 00:00 [revised]
PHST- 2018/01/22 00:00 [accepted]
PHST- 2018/01/29 06:00 [pubmed]
PHST- 2019/05/24 06:00 [medline]
PHST- 2018/01/29 06:00 [entrez]
AID - S0891-5849(18)30036-4 [pii]
AID - 10.1016/j.freeradbiomed.2018.01.026 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2018 May 1;119:34-44. doi: 
      10.1016/j.freeradbiomed.2018.01.026. Epub 2018 Jan 31.