Synaptosomal lactate Dehydrogenase Isoenzyme composition is shifted toward aerobic forms in primate brain evolution

Tetyana Duka, Sarah M. Anderson, Zachary Collins, Mary Ann Raghanti, John J. Ely, Patrick R. Hof, Derek E. Wildman, Morris Goodman, Lawrence I. Grossman, Chet C. Sherwood

Research output: Contribution to journalArticlepeer-review


With the evolution of a relatively large brain size in haplorhine primates (i.e. tarsiers, monkeys, apes, and humans), there have been associated changes in the molecular machinery that delivers energy to the neocortex. Here we investigated variation in lactate dehydrogenase (LDH) expression and isoenzyme composition of the neocortex and striatum in primates using quantitative Western blotting and isoenzyme analysis of total homogenates and synaptosomal fractions. Analysis of isoform expression revealed that LDH in synaptosomal fractions from both forebrain regions shifted towards a predominance of the heart-type, aerobic isoform LDH-B among haplorhines as compared to strepsirrhines (i.e. lorises and lemurs), while in the total homogenate of the neocortex and striatum there was no significant difference in LDH isoenzyme composition between the primate suborders. The largest increase occurred in synapse-associated LDH-B expression in the neocortex, with an especially remarkable elevation in the ratio of LDH-B/LDH-A in humans. The phylogenetic variation in the ratio of LDH-B/LDH-A was correlated with species-typical brain mass but not the encephalization quotient. A significant LDH-B increase in the subneuronal fraction from haplorhine neocortex and striatum suggests a relatively higher rate of aerobic glycolysis that is linked to synaptosomal mitochondrial metabolism. Our results indicate that there is a differential composition of LDH isoenzymes and metabolism in synaptic terminals that evolved in primates to meet increased energy requirements in association with brain enlargement.

Original languageEnglish (US)
Pages (from-to)216-230
Number of pages15
JournalBrain, behavior and evolution
Issue number3
StatePublished - Jun 2014
Externally publishedYes


  • Brain
  • Haplorhines
  • Lactate dehydrogenase
  • Metabolism
  • Strepsirrhines
  • Synaptosome

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Behavioral Neuroscience


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