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Published on: January 11, 2013
Neurochemical changes in the developing rat hippocampus during prolonged hypoglycemia
Raghavendra Rao1, Kathleen Ennis, Jeffery D Long
1Division of Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA. raoxx017@umn.edu
Insights
Hypoglycemia in developing rat hippocampus maintains energy homeostasis through compensatory shifts in substrates like glutamate and glutamine. This neurochemical adaptation preserves neuronal integrity during prolonged low blood glucose.
Area of Science:
- Neuroscience
- Biochemistry
- Developmental Biology
Background:
- Hypoglycemia during development poses risks for neurodevelopmental deficits.
- The impact of hypoglycemia on the developing hippocampus remains unclear.
Purpose of the Study:
- To investigate the neurochemical changes in the developing hippocampus during prolonged hypoglycemia.
- To understand the brain's energy substrate utilization and homeostasis mechanisms under hypoglycemic conditions.
Main Methods:
- Insulin-induced hypoglycemia in 14-day-old rats for 180 minutes.
- In vivo 1H NMR spectroscopy to measure hippocampal energy substrates, amino acids, and phosphocreatine.
- Monitoring blood glucose and brain glucose levels.
Main Results:
- Neuroglycopenia occurred, but the phosphocreatine/creatine ratio remained stable initially, indicating sustained energy supply.
- Lactate decreased, while glutamine and glutamate became primary energy substrates after 60 minutes.
- Energy failure (decreased PCr/Cr) was observed only after significant amino acid depletion; N-acetylaspartate remained unchanged, suggesting preserved neuronal integrity.
Conclusions:
- The developing hippocampus employs compensatory neurochemical strategies to maintain energy homeostasis during prolonged hypoglycemia.
- Glutamine, glutamate, and eventually aspartate serve as crucial energy substrates when glucose is unavailable.
- Neuronal integrity appears preserved during hypoglycemia due to these adaptive mechanisms.
Abstract:
Hypoglycemia is common during development and is associated with the risk of neurodevelopmental deficits in human infants. The effects of hypoglycemia on the developing hippocampus are poorly understood. The sequential changes in energy substrates, amino acids and phosphocreatine were measured from the hippocampus during 180 min of insulin-induced hypoglycemia (blood glucose < 2.5 mmol/L) in 14-day-old rats using in vivo(1)H NMR spectroscopy. Hypoglycemia resulted in neuroglycopenia (brain glucose < 0.5 micromol/g). However, the phosphocreatine/creatine (PCr/Cr) ratio was maintained in the physiological range until approximately 150 min of hypoglycemia, indicating that energy supply was sufficient to meet the energy demands. Lactate concentration decreased soon after the onset of neuroglycopenia. Beyond 60 min, glutamine and glutamate became the major energy substrates. A precipitous decrease in the PCr/Cr ratio, indicative of impending energy failure occurred only after significant depletion of these amino acids. Once glutamate and glutamine were significantly exhausted, aspartate became the final energy source. N-acetylaspartate concentration remained unaltered, suggesting preservation of neuronal/mitochondrial integrity during hypoglycemia. Correction of hypoglycemia normalized the PCr/Cr ratio and partially restored the amino acids to pre-hypoglycemia levels. Compensatory neurochemical changes maintain energy homeostasis during prolonged hypoglycemia in the developing hippocampus.
