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

作者：Gybina Anna A; Prohaska Joseph R^*

来源：Metabolic Brain Disease, 2009, 24(2): 299-310.

DOI：10.1007/s11011-009-9135-8

• Copper-deficient
• Rat pup
• Cerebellum
• Lactate
• Blood
• Dichloroacetate

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.

• 出版日期2009-6