Metabolic Brain Disease

, Volume 24, Issue 2, pp 299–310

Augmented cerebellar lactate in copper deficient rat pups originates from both blood and cerebellum

Original Paper

Abstract

Copper (Cu) is essential for proper brain development, particularly the cerebellum, and functions as a cofactor for enzymes including mitochondrial cytochrome c oxidase (CCO). Cu deficiency severely limits CCO activity. Augmented lactate in brain of Cu deficient (Cu-) humans and cerebella of Cu- rats is though to originate from impaired mitochondria. However, brain lactate may also originate from elevated blood lactate. The hypothesis that cerebellar lactate originates from elevated blood lactate in Cu- rat pups was tested. Analysis of Cu- and Cu adequate (Cu+) rat pups (experiment I) revealed blood lactate was elevated in Cu- rat pups and cerebellar lactate levels were closely correlated to blood lactate concentration. A second rat experiment (experiment II) assessed Cu- cerebellar lactate without the confounding factor of elevated blood lactate. Blood lactate levels of Cu- rat pups in experiment II were equal to those of controls; however, Cu- cerebellar lactate was still elevated, suggesting mitochondrial impairment by Cu deficiency. Treatment of rat pups with dichloroacetate (DCA), an activator of mitochondrial pyruvate dehydrogenase complex (PDC), lowered Cu- cerebellar lactate to control levels suggesting PDC inhibition is a site of mitochondrial impairment in Cu- cerebella. Results suggest Cu- cerebellar lactate originates from blood and cerebellum.

Keywords

Copper-deficient Rat pup Cerebellum Lactate Blood Dichloroacetate 

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologyUniversity of Minnesota Medical School DuluthDuluthUSA

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