PMID- 26968531
OWN - NLM
STAT- MEDLINE
DCOM- 20170615
LR  - 20181113
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 139 Suppl 2
IP  - Suppl Suppl 2
DP  - 2016 Oct
TI  - Bioenergetics and redox adaptations of astrocytes to neuronal activity.
PG  - 115-125
LID - 10.1111/jnc.13486 [doi]
AB  - Neuronal activity is a high-energy demanding process recruiting all neural cells 
      that adapt their metabolism to sustain the energy and redox balance of neurons. 
      During neurotransmission, synaptic cleft glutamate activates its receptors in 
      neurons and in astrocytes, before being taken up by astrocytes through energy 
      costly transporters. In astrocytes, the energy requirement for glutamate influx 
      is likely to be met by glycolysis. To enable this, astrocytes are constitutively 
      glycolytic, robustly expressing 
      6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3), an enzyme that 
      is negligibly present in neurons by continuous degradation because of the 
      ubiquitin-proteasome pathway via anaphase-promoting complex/cyclosome (APC)-Cdh1. 
      Additional factors contributing to the glycolytic frame of astrocytes may include 
      5'-AMP-activated protein kinase (AMPK), hypoxia-inducible factor-1 (HIF-1), 
      pyruvate kinase muscle isoform-2 (PKM2), pyruvate dehydrogenase kinase-4 (PDK4), 
      lactate dehydrogenase-B, or monocarboxylate transporter-4 (MCT4). 
      Neurotransmission-associated messengers, such as nitric oxide or ammonium, 
      stimulate lactate release from astrocytes. Astrocyte-derived glycolytic lactate 
      thus sustains the energy needs of neurons, which in contrast to astrocytes mainly 
      rely on oxidative phosphorylation. Neuronal activity unavoidably triggers 
      reactive oxygen species, but the antioxidant defense of neurons is weak; hence, 
      they use glucose for oxidation through the pentose-phosphate pathway to preserve 
      the redox status. Furthermore, neural activity is coupled with erythroid-derived 
      erythroid-derived 2-like 2 (Nrf2) mediated transcriptional activation of 
      antioxidant genes in astrocytes, which boost the de novo glutathione biosynthesis 
      in neighbor neurons. Thus, the bioenergetics and redox programs of astrocytes are 
      adapted to sustain neuronal activity and survival. Developing therapeutic 
      strategies to interfere with these pathways may be useful to combat neurological 
      diseases. Our current knowledge on brain's management of bioenergetics and redox 
      requirements associated with neural activity is herein revisited. The 
      astrocyte-neuronal lactate shuttle (ANLS) explains the energy needs of 
      neurotransmission. Furthermore, neurotransmission unavoidably triggers increased 
      mitochondrial reactive oxygen species in neurons. By coupling glutamatergic 
      activity with transcriptional activation of antioxidant genes, astrocytes provide 
      neurons with neuroprotective glutathione through an astrocyte-neuronal 
      glutathione shuttle (ANGS). This article is part of the 60th Anniversary special 
      issue.
CI  - (c) 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd 
      on behalf of International Society for Neurochemistry.
FAU - Bolanos, Juan P
AU  - Bolanos JP
AD  - Institute of Functional Biology and Genomics (IBFG), University of 
      Salamanca-CSIC-IBSAL, Salamanca, Spain. jbolanos@usal.es.
LA  - eng
GR  - R21 DA037678/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20160310
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Animals
MH  - Astrocytes/*metabolism
MH  - Brain/metabolism
MH  - Energy Metabolism/*physiology
MH  - Humans
MH  - Neurons/*metabolism
MH  - Oxidation-Reduction
MH  - Reactive Oxygen Species/metabolism
MH  - Synapses/metabolism
PMC - PMC5018236
MID - NIHMS746585
OTO - NOTNLM
OT  - AMPK
OT  - GSH
OT  - Cdh1
OT  - Glycolysis
OT  - Nrf2
OT  - PFKFB3
EDAT- 2016/11/01 06:00
MHDA- 2017/06/16 06:00
PMCR- 2016/11/04
CRDT- 2016/03/13 06:00
PHST- 2015/10/22 00:00 [received]
PHST- 2015/11/19 00:00 [revised]
PHST- 2015/11/23 00:00 [accepted]
PHST- 2016/11/01 06:00 [pubmed]
PHST- 2017/06/16 06:00 [medline]
PHST- 2016/03/13 06:00 [entrez]
PHST- 2016/11/04 00:00 [pmc-release]
AID - JNC13486 [pii]
AID - 10.1111/jnc.13486 [doi]
PST - ppublish
SO  - J Neurochem. 2016 Oct;139 Suppl 2(Suppl Suppl 2):115-125. doi: 10.1111/jnc.13486. 
      Epub 2016 Mar 10.