PMID- 25863252
OWN - NLM
STAT- MEDLINE
DCOM- 20160201
LR  - 20220129
IS  - 1932-7420 (Electronic)
IS  - 1550-4131 (Print)
IS  - 1550-4131 (Linking)
VI  - 21
IP  - 4
DP  - 2015 Apr 7
TI  - Dependence of hippocampal function on ERRgamma-regulated mitochondrial metabolism.
PG  - 628-36
LID - S1550-4131(15)00107-2 [pii]
LID - 10.1016/j.cmet.2015.03.004 [doi]
AB  - Neurons utilize mitochondrial oxidative phosphorylation (OxPhos) to generate 
      energy essential for survival, function, and behavioral output. Unlike most cells 
      that burn both fat and sugar, neurons only burn sugar. Despite its importance, 
      how neurons meet the increased energy demands of complex behaviors such as 
      learning and memory is poorly understood. Here we show that the estrogen-related 
      receptor gamma (ERRgamma) orchestrates the expression of a distinct neural gene 
      network promoting mitochondrial oxidative metabolism that reflects the 
      extraordinary neuronal dependence on glucose. ERRgamma(-/-) neurons exhibit decreased 
      metabolic capacity. Impairment of long-term potentiation (LTP) in ERRgamma(-/-) 
      hippocampal slices can be fully rescued by the mitochondrial OxPhos substrate 
      pyruvate, functionally linking the ERRgamma knockout metabolic phenotype and memory 
      formation. Consistent with this notion, mice lacking neuronal ERRgamma in cerebral 
      cortex and hippocampus exhibit defects in spatial learning and memory. These 
      findings implicate neuronal ERRgamma in the metabolic adaptations required for memory 
      formation.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Pei, Liming
AU  - Pei L
AD  - Center for Mitochondrial and Epigenomic Medicine, Department of Pathology and 
      Laboratory Medicine, Children's Hospital of Philadelphia and Perelman School of 
      Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic 
      address: lpei@mail.med.upenn.edu.
FAU - Mu, Yangling
AU  - Mu Y
AD  - Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 
      92037, USA.
FAU - Leblanc, Mathias
AU  - Leblanc M
AD  - Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 
      92037, USA.
FAU - Alaynick, William
AU  - Alaynick W
AD  - Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 
      92037, USA.
FAU - Barish, Grant D
AU  - Barish GD
AD  - Division of Endocrinology, Metabolism, and Molecular Medicine, Department of 
      Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 
      60611, USA.
FAU - Pankratz, Matthew
AU  - Pankratz M
AD  - Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 
      92037, USA.
FAU - Tseng, Tiffany W
AU  - Tseng TW
AD  - Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 
      92037, USA.
FAU - Kaufman, Samantha
AU  - Kaufman S
AD  - Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 
      92037, USA; Howard Hughes Medical Institute, Salk Institute for Biological 
      Studies, La Jolla, CA 92037, USA.
FAU - Liddle, Christopher
AU  - Liddle C
AD  - Storr Liver Unit, Westmead Millennium Institute and University of Sydney, 
      Westmead Hospital, Westmead, New South Wales 2145, Australia.
FAU - Yu, Ruth T
AU  - Yu RT
AD  - Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 
      92037, USA.
FAU - Downes, Michael
AU  - Downes M
AD  - Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 
      92037, USA.
FAU - Pfaff, Samuel L
AU  - Pfaff SL
AD  - Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 
      92037, USA; Howard Hughes Medical Institute, Salk Institute for Biological 
      Studies, La Jolla, CA 92037, USA.
FAU - Auwerx, Johan
AU  - Auwerx J
AD  - Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Federale de 
      Lausanne, 1015 Lausanne, Switzerland.
FAU - Gage, Fred H
AU  - Gage FH
AD  - Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 
      92037, USA.
FAU - Evans, Ronald M
AU  - Evans RM
AD  - Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 
      92037, USA; Howard Hughes Medical Institute, Salk Institute for Biological 
      Studies, La Jolla, CA 92037, USA. Electronic address: evans@salk.edu.
LA  - eng
SI  - GEO/GSE47135
GR  - R01 HL105278/HL/NHLBI NIH HHS/United States
GR  - CA014195/CA/NCI NIH HHS/United States
GR  - MH090258/MH/NIMH NIH HHS/United States
GR  - T32 GM007507/GM/NIGMS NIH HHS/United States
GR  - DK090962/DK/NIDDK NIH HHS/United States
GR  - P30 DK063491/DK/NIDDK NIH HHS/United States
GR  - R37 DK057978/DK/NIDDK NIH HHS/United States
GR  - HL105278/HL/NHLBI NIH HHS/United States
GR  - HHMI_/Howard Hughes Medical Institute/United States
GR  - P30 CA014195/CA/NCI NIH HHS/United States
GR  - R01 MH090258/MH/NIMH NIH HHS/United States
GR  - DK057978/DK/NIDDK NIH HHS/United States
GR  - R24 DK090962/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Metab
JT  - Cell metabolism
JID - 101233170
RN  - 0 (Esrrg protein, mouse)
RN  - 0 (Galactosides)
RN  - 0 (Indoles)
RN  - 0 (Receptors, Estrogen)
RN  - 8558G7RUTR (Pyruvic Acid)
RN  - V595OG374W (5-bromo-4-chloro-3-indolyl beta-galactoside)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Chromatin Immunoprecipitation
MH  - Galactosides
MH  - Gene Knockout Techniques
MH  - Glycolysis/physiology
MH  - Hippocampus/metabolism/*physiology
MH  - Indoles
MH  - Long-Term Potentiation/*physiology
MH  - Memory/physiology
MH  - Mice
MH  - Microarray Analysis
MH  - Mitochondria/*metabolism
MH  - Neurons/*metabolism
MH  - Pyruvic Acid
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Estrogen/*metabolism
MH  - Spatial Learning/physiology
PMC - PMC4393848
MID - NIHMS670603
EDAT- 2015/04/12 06:00
MHDA- 2016/02/02 06:00
PMCR- 2016/04/07
CRDT- 2015/04/12 06:00
PHST- 2014/03/14 00:00 [received]
PHST- 2015/01/16 00:00 [revised]
PHST- 2015/02/27 00:00 [accepted]
PHST- 2015/04/12 06:00 [entrez]
PHST- 2015/04/12 06:00 [pubmed]
PHST- 2016/02/02 06:00 [medline]
PHST- 2016/04/07 00:00 [pmc-release]
AID - S1550-4131(15)00107-2 [pii]
AID - 10.1016/j.cmet.2015.03.004 [doi]
PST - ppublish
SO  - Cell Metab. 2015 Apr 7;21(4):628-36. doi: 10.1016/j.cmet.2015.03.004.