Dichloroacetate increases glucose use and decreases lactate in developing rat brain

Alexander L Miller, John P. Hatch, Thomas J. Prihoda

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Dichloroacetate (DCA) activates pyruvate dehydrogenase (PDH) by inhibiting PDH kinase. Neutralized DCA (100 mg/kg) or saline was intravenously administered to 20 to 25-day-old rats (50-75 g). Fifteen minutes later a mixture of [6-14C]glucose and [3H]fluorodeoxyglucose (FDG) was administered intravenously and the animals were sacrificed by microwave irradiation (2450 MHz, 8.0 kW, 0.6-0.8 sec) after 2 or 5 min. Brain regional rates of glucose use and metabolite levels were determined. DCA-treated rats had increased rates of glucose use in all regions studied (cortex, thalamus, striatum, and brain stem), with an average increase of 41%. Lactate levels were lower in all regions, by an average of 35%. There were no significant changes in levels of ATP, creatine phosphate, or glycogen in any brain region. Blood levels of lactate did not differ significantly between the DCA- and the saline-treated groups. Blood glucose levels were higher in the DCA group. In rats sacrificed by freeze-blowing, DCA treatment caused lower brain levels of both lactate and pyruvate. These results cannot be explained by any systemic effect of DCA. Rather, it appears that in the immature rat, DCA treatment results in activation of brain PDH, increased metabolism of brain pyruvate and lactate, and a resulting increase in brain glycolytic rate.

Original languageEnglish (US)
Pages (from-to)195-204
Number of pages10
JournalMetabolic Brain Disease
Volume5
Issue number4
DOIs
StatePublished - Dec 1990

Fingerprint

Rats
Lactic Acid
Brain
Pyruvic Acid
Glucose
Oxidoreductases
Phosphocreatine
Microwaves
Microwave irradiation
Thalamus
Glycogen
Brain Stem
Metabolites
Blow molding
Blood Glucose
Metabolism
Adenosine Triphosphate
Animals
Blood
Chemical activation

Keywords

  • brain
  • development
  • dichloroacetate
  • glucose
  • lactate

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Biochemistry

Cite this

Dichloroacetate increases glucose use and decreases lactate in developing rat brain. / Miller, Alexander L; Hatch, John P.; Prihoda, Thomas J.

In: Metabolic Brain Disease, Vol. 5, No. 4, 12.1990, p. 195-204.

Research output: Contribution to journalArticle

Miller, Alexander L ; Hatch, John P. ; Prihoda, Thomas J. / Dichloroacetate increases glucose use and decreases lactate in developing rat brain. In: Metabolic Brain Disease. 1990 ; Vol. 5, No. 4. pp. 195-204.
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