Short-lived diabetes in the young-adult ZDF rat does not exacerbate neuronal Ca2+ biomarkers of aging

•Neuronal Calcium dysregulation is a hallmark of aging and AD.•The AHP, a neuronal calcium biomarker of aging is increased with age.•Male ZDF rats with sustained hyperglycemia show no signs of hippocampal Ca2+ dysregulation.•Our results suggest aging is an important factor in diabetes-mediated cognitive decline.

Results from clinical studies provide evidence that cognitive changes relatively late in life may be traced to antecedent conditions including diabetes, obesity, a sedentary lifestyle, and an atherogenic diet. As such, several traits of Type 2 diabetes (T2DM) could be considered pathogenic factors of aging, contributing to age-dependent cognitive decline and our susceptibility to Alzheimer's disease. It appears that both the duration of metabolic condition and the age of the individual, together can contribute to the potential impact on peripheral as well as brain health. Because of robust evidence that in animal models of aging, Ca2+ dysregulation alters neuronal health, synaptic plasticity, and learning and memory processes, we tested the hypothesis that peripheral metabolic dysregulation could exacerbate Ca2+ dysfunction in hippocampal CA1 neurons. Using intracellular/ extracellular electrophysiological and Ca2+ imaging techniques, we show that Ca2+levels at rest or during synaptic stimulation, the Ca2+-dependent afterhyperpolarization, baseline field potentials, and short-term synaptic plasticity were not significantly altered in young-adult male Zucker diabetic fatty rats compare to their lean counterparts. Our observations suggest that early phases of T2DM characterized by high levels of glucose and insulin may be too transient to alter hippocampal CA1 physiology in this animal model of diabetes. These results are supported by clinical data showing that longer T2DM duration can have greater negative impact on cognitive functions.This article is part of a Special Issue entitled SI: Brain and Memory.