Decreased in vitro mitochondrial function is associated with enhanced brain metabolism, blood flow, and memory in Surf1-deficient mice.

TitleDecreased in vitro mitochondrial function is associated with enhanced brain metabolism, blood flow, and memory in Surf1-deficient mice.
Publication TypeJournal Article
Year of Publication2013
AuthorsLin, A-L, Pulliam, DA, Deepa, SS, Halloran, JJ, Hussong, SA, Burbank, RR, Bresnen, A, Liu, Y, Podlutskaya, N, Soundararajan, A, Muir, E, Duong, TQ, Bokov, AF, Viscomi, C, Zeviani, M, Richardson, AG, Van Remmen, H, Fox, PT, Galvan, V
JournalJ Cereb Blood Flow Metab
Volume33
Issue10
Pagination1605-11
Date Published2013 Oct
ISSN1559-7016
KeywordsAdenosine Triphosphate, Animals, Behavior, Animal, Blood Flow Velocity, Brain, Cerebrovascular Circulation, Glucose, Hydrogen Peroxide, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Maze Learning, Membrane Proteins, Memory, Mice, Mice, Knockout, Mitochondria, Mitochondrial Proteins, Oxygen Consumption
Abstract

Recent studies have challenged the prevailing view that reduced mitochondrial function and increased oxidative stress are correlated with reduced longevity. Mice carrying a homozygous knockout (KO) of the Surf1 gene showed a significant decrease in mitochondrial electron transport chain Complex IV activity, yet displayed increased lifespan and reduced brain damage after excitotoxic insults. In the present study, we examined brain metabolism, brain hemodynamics, and memory of Surf1 KO mice using in vitro measures of mitochondrial function, in vivo neuroimaging, and behavioral testing. We show that decreased respiration and increased generation of hydrogen peroxide in isolated Surf1 KO brain mitochondria are associated with increased brain glucose metabolism, cerebral blood flow, and lactate levels, and with enhanced memory in Surf1 KO mice. These metabolic and functional changes in Surf1 KO brains were accompanied by higher levels of hypoxia-inducible factor 1 alpha, and by increases in the activated form of cyclic AMP response element-binding factor, which is integral to memory formation. These findings suggest that Surf1 deficiency-induced metabolic alterations may have positive effects on brain function. Exploring the relationship between mitochondrial activity, oxidative stress, and brain function will enhance our understanding of cognitive aging and of age-related neurologic disorders.

DOI10.1038/jcbfm.2013.116
Alternate JournalJ. Cereb. Blood Flow Metab.
Citation Key10.1038/jcbfm.2013.116
PubMed ID23838831
PubMed Central IDPMC3790931
Grant ListT32 AG021890 / AG / NIA NIH HHS / United States
P30 AG013319 / AG / NIA NIH HHS / United States
T32 HL007446 / HL / NHLBI NIH HHS / United States
UL1 TR000149 / TR / NCATS NIH HHS / United States
KL2 UL1TR000149 / TR / NCATS NIH HHS / United States
T32AG21890 / AG / NIA NIH HHS / United States
UL1 TR001120 / TR / NCATS NIH HHS / United States
K01AG040164 / AG / NIA NIH HHS / United States
K01 AG040164 / AG / NIA NIH HHS / United States