Dichloroacetate increases glucose use and decreases lactate in developing rat brain

Journal Article · Sat Dec 01 00:00:00 EST 1990 · Metabolic Brain Disease; (USA)

DOI:https://doi.org/10.1007/BF00997073· OSTI ID:5684189

Miller, A L; Hatch, J P; Prihoda, T J ^[1]

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1. Univ. of Texas Health Science Center, San Antonio (USA)

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 (50-75g). Fifteen minutes later a mixture of {sup 6-14}C glucose and {sup 3}H 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.

• OSTI ID: 5684189
• Journal Information: Metabolic Brain Disease; (USA), Vol. 5:4; ISSN 0885-7490
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ACETATES
BIOCHEMICAL REACTION KINETICS
GLUCOSE
METABOLISM
LACTATES
BIOSYNTHESIS
OXIDOREDUCTASES
ENZYME ACTIVITY
BRAIN
INHIBITION
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALDEHYDES
ANIMALS
BODY
CARBOHYDRATES
CARBOXYLIC ACID SALTS
CENTRAL NERVOUS SYSTEM
ENZYMES
HEXOSES
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
MAMMALS
MONOSACCHARIDES
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
REACTION KINETICS
RODENTS
SACCHARIDES
SYNTHESIS
VERTEBRATES
550501* - Metabolism- Tracer Techniques