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

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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.

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Acknowledgments

We thank Margaret Boderius and Joshua Pyatskowit for their excellent technical assistance. This research was supported by NIH HD-039708 and the University of Minnesota Doctoral Dissertation Fellowship.

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  1. Department of Biochemistry and Molecular Biology, University of Minnesota Medical School Duluth, 1035 University Drive, Duluth, MN, 55812, USA

    Anna A. Gybina & Joseph R. Prohaska

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  1. Anna A. Gybina
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  2. Joseph R. Prohaska
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Correspondence to Joseph R. Prohaska.

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Gybina, A.A., Prohaska, J.R. Augmented cerebellar lactate in copper deficient rat pups originates from both blood and cerebellum. Metab Brain Dis 24, 299–310 (2009). https://doi.org/10.1007/s11011-009-9135-8

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