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Published on: January 11, 2013
Repetitive hypoglycemia in young rats impairs hippocampal long-term potentiation
Kelvin A Yamada1, Nicholas Rensing, Yukitoshi Izumi
1Department of Neurology, Box 8111, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. YamadaK@neuro.wustl.edu
Insights
Repetitive insulin-induced hypoglycemia in young rats impaired hippocampal synaptic plasticity without causing significant neuron death. This suggests a potential mechanism for cognitive deficits in diabetic children.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Cognitive dysfunction in young diabetic children is poorly understood.
- Potential mechanisms include synaptic dysfunction due to insulin-induced hypoglycemia.
Purpose of the Study:
- To investigate the effects of repetitive insulin-induced hypoglycemia on synaptic plasticity in the developing rat brain.
- To examine potential neuron death and neurogenesis changes following hypoglycemic events.
Main Methods:
- Developed a rat model of repetitive insulin-induced hypoglycemia (postnatal days 21-25).
- Assessed hippocampal long-term potentiation (LTP) as a measure of synaptic plasticity.
- Quantified neuron death using Fluoro-Jade B staining and neurogenesis via bromodeoxyuridine incorporation.
Main Results:
- Repetitive hypoglycemia caused modest cortical neuron death but no hippocampal neuron death.
- Neurogenesis in the hippocampal dentate granule cell region remained unchanged.
- While baseline synaptic responses were normal, long-term potentiation could not be induced in hippocampal slices from hypoglycemic rats.
Conclusions:
- Repetitive hypoglycemia in the developing brain selectively impairs hippocampal synaptic plasticity without significant cell death.
- This impaired synaptic plasticity may underlie cognitive deficits observed in young diabetic children.
- Cortical neuron death could contribute to other neurological and psychological issues in diabetic children.
Abstract:
Mechanisms underlying cognitive dysfunction in young diabetic children are poorly understood, and may include synaptic dysfunction from insulin-induced hypoglycemia. We developed a model of repetitive insulin-induced hypoglycemia in young rats and examined hippocampal long-term potentiation, an electrophysiologic assay of synaptic plasticity, 3-5 d after the last hypoglycemic event. Three hypoglycemic events between postnatal d 21-25 produced modest cortical (17 +/- 2.9 dead neurons per section in parasagittal cortex), but not hippocampal, neuron death quantified by Fluoro-Jade B staining. There was no change in neurogenesis in the hippocampal dentate granule cell region by quantification of bromodeoxyuridine incorporation. Although normal baseline hippocampal synaptic responses were elicited from hippocampal slices from hypoglycemic animals, long-term synaptic potentiation could not be induced in hippocampal slices from rats subjected to hypoglycemia. These results suggest that repetitive hypoglycemia in the developing brain can cause selective impairment of synaptic plasticity in the absence of cell death, and without complete disruption of basal synaptic transmission. We speculate that impaired synaptic plasticity in the hippocampus caused by repetitive hypoglycemia could underlie memory and cognitive deficits observed in young diabetic children, and that cortical neuron death caused by repetitive hypoglycemia in the developing brain may contribute to other neurologic, cognitive, and psychological problems sometimes encountered in diabetic children.
