Dichloroacetate increases glucose use and decreases lactate in developing rat brain

Area of Science:

• Neuroscience
• Biochemistry
• Developmental Biology

Background:

• Dichloroacetate (DCA) is known to activate pyruvate dehydrogenase (PDH) by inhibiting PDH kinase.
• The role and metabolic effects of DCA in the immature brain are not fully understood.

Purpose of the Study:

• To investigate the effects of DCA on glucose metabolism and metabolite levels in the immature rat brain.
• To determine if DCA-induced metabolic changes are systemic or specific to the brain.

Main Methods:

• Intravenous administration of DCA (100 mg/kg) or saline to 20-25-day-old rats.
• Measurement of brain regional glucose utilization using [6-14C]glucose and [3H]fluorodeoxyglucose (FDG).
• Determination of brain metabolite levels (lactate, pyruvate, ATP, creatine phosphate, glycogen) via microwave irradiation or freeze-blowing.

Main Results:

• DCA treatment significantly increased glucose utilization in all studied brain regions (cortex, thalamus, striatum, brain stem) by an average of 41%.
• Brain lactate levels decreased by an average of 35% in DCA-treated rats, with lower lactate and pyruvate observed in freeze-blown brains.
• No significant changes in brain ATP, creatine phosphate, or glycogen levels were observed; blood lactate remained unchanged, while blood glucose increased.

Conclusions:

• DCA activates pyruvate dehydrogenase (PDH) in the immature rat brain, leading to increased glucose metabolism.
• The observed metabolic changes are brain-specific and not due to systemic effects of DCA.
• DCA treatment enhances brain glycolytic rate in immature rats by increasing pyruvate and lactate metabolism.