Hypoglycemia in the Developing Diabetic Brain

Washington University, Saint Louis MO

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Abstract

DESCRIPTION (provided by applicant): Type I diabetes mellitus is common in children, and diabetic children are at risk for acquiring various types of mild to severe cognitive deficits. The underlying causes that predispose diabetic children to cognitive impairment, and the factors that influence the type and severity of cognitive impairment are poorly understood, but may in part be related to episodes of hypoglycemia or from the effects of diabetes at critical stages of neural development. For this reason we propose to study the injurious effects of hypoglycemia and diabetes upon developing animals. Our central hypothesis is that the developing brain is susceptible to hypoglycemia- and diabetes-induced structural and functional disturbances, which account for cognitive deficits observed in some diabetic children. We will subject developing and mature ThylGFP-M transgenic mice to hypoglycemia or diabetes, and evaluate synaptic plasticity by electrophysiological recording, and alterations in dendritic and synaptic structure by fluorescence confocal microscopy and immunohistochemistry to identify functional and structural abnormalities that could account for neurological and cognitive impairment. This model will facilitate subsequent studies investigating mechanisms of hypoglycemia- and diabetes-induced brain injury in a more comprehensive way in vivo, including investigating neuroprotective interventions, outcome assessment of animals using well-established behavioral outcome measures (e.g., spatial motor, memory, leaning tasks), and finally addressing whether hypoglycemia and diabetes have synergistic injurious effects upon the developing brain.