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Dependence of hippocampal function on ERR?-regulated mitochondrial metabolism.

ABSTRACT: 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 (ERR?) orchestrates the expression of a distinct neural gene network promoting mitochondrial oxidative metabolism that reflects the extraordinary neuronal dependence on glucose. ERR?(-/-) neurons exhibit decreased metabolic capacity. Impairment of long-term potentiation (LTP) in ERR?(-/-) hippocampal slices can be fully rescued by the mitochondrial OxPhos substrate pyruvate, functionally linking the ERR? knockout metabolic phenotype and memory formation. Consistent with this notion, mice lacking neuronal ERR? in cerebral cortex and hippocampus exhibit defects in spatial learning and memory. These findings implicate neuronal ERR? in the metabolic adaptations required for memory formation.

SUBMITTER: Pei L

PROVIDER: S-EPMC4393848 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Dependence of hippocampal function on ERRγ-regulated mitochondrial metabolism.

Pei Liming L Mu Yangling Y Leblanc Mathias M Alaynick William W Barish Grant D GD Pankratz Matthew M Tseng Tiffany W TW Kaufman Samantha S Liddle Christopher C Yu Ruth T RT Downes Michael M Pfaff Samuel L SL Auwerx Johan J Gage Fred H FH Evans Ronald M RM

Cell metabolism 20150401 4

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 (ERRγ) orchestrates the expression of a distinct neural gene network promoting mitochondria ...[more]

PMID: 25863252

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Project description:KEY POINTS:Skeletal muscle energy requirements increase at birth but little is known regarding the development of mitochondria that provide most of the cellular energy as ATP. Thyroid hormones are known regulators of adult metabolism and are important in driving several aspects of fetal development, including muscle fibre differentiation. Mitochondrial density and the abundance of mitochondrial membrane proteins in skeletal muscle increased during late gestation. However, mitochondrial functional capacity, measured as oxygen consumption rate, increased primarily after birth. Fetal hypothyroidism resulted in significant reductions in mitochondrial function and density in skeletal muscle before birth. Mitochondrial function matures towards birth and is dependent on the presence of thyroid hormones, with potential implications for the health of pre-term and hypothyroid infants. ABSTRACT:Birth is a significant metabolic challenge with exposure to a pro-oxidant environment and the increased energy demands for neonatal survival. This study investigated the development of mitochondrial density and activity in ovine biceps femoris skeletal muscle during the perinatal period and examined the role of thyroid hormones in these processes. Muscle capacity for oxidative phosphorylation increased primarily after birth but was accompanied by prepartum increases in mitochondrial density and the abundance of electron transfer system (ETS) complexes I-IV and ATP-synthase as well as by neonatal upregulation of uncoupling proteins. This temporal disparity between prepartum maturation and neonatal upregulation of mitochondrial oxidative capacity may protect against oxidative stress associated with birth while ensuring energy availability to the neonate. Fetal thyroid hormone deficiency reduced oxidative phosphorylation and prevented the prepartum upregulation of mitochondrial density and ETS proteins in fetal skeletal muscle. Overall, the data show that mitochondrial function matures over the perinatal period and is dependent on thyroid hormones, with potential consequences for neonatal viability and adult metabolic health.

Dataset Information

Dependence of hippocampal function on ERR?-regulated mitochondrial metabolism.

Publications

Dependence of hippocampal function on ERRγ-regulated mitochondrial metabolism.

Similar Datasets

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