Elevated Brain Glucose and Glycogen Concentrations in an Animal Model of Depression

Abstract

Introduction: Recent data indicate that there is a link between depression and diabetes and that excess glucocorticoids may play an underlying role in the pathogenesis of both of these diseases. The aim of the present study was to determine whether there are any alterations in glucose, glycogen, glucose transporters, insulin, insulin receptors or corticosterone concentrations in the hippocampus and frontal cortex in a prenatal stress rat model of depression. Methods: Male rats whose mothers had been subjected to stress and control animals were subjected to the Porsolt test to verify the experimental model. Next, some of the rats were subjected to acute stress and/or were administered glucose. Glucose, glycogen, corticosterone, insulin, insulin receptor, phospho-insulin receptor and glucose transporter (GLUT1, GLUT3 and GLUT4) concentrations were assayed. Results: Prenatally stressed rats exhibited glucose and glycogen concentrations in both investigated brain structures that exceeded those of the control animals. Prenatal stress also increased the levels of glucose transporters - GLUT1 in both tissues and GLUT4 in the frontal cortex. The changes in the prenatally stressed rats were more prominent in the animals that were subjected to stress or glucose loading in adulthood. Conclusion: The increase in carbohydrate brain concentrations evoked by prenatal stress may result from changes in the amounts of glucose transporters, especially GLUT1. Moreover, the obtained results support the hypothesis that stress during the perinatal period permanently increases the sensitivity of brain tissue to factors that act in adulthood.

Brain glucose metabolism in an animal model of depression

“…However, it should be taken into account that various processes associated with glucose metabolism occur in different cell compartments, and their role in disturbed neuronal and glial function in depression is still poorly understood. Our results demonstrate that prenatal stress enhanced mainly glucose transporter 1 (Detka et al, 2014) which occurs in astrocytes but not in neurons, and changed the process of glycolysis which also took place mainly in the astrocytes. These data suggest that the metabolic disturbance is related rather to astrocytes than neurons in this animal model of depression.…”

“…Previously, we found elevated brain glucose and glycogen levels in the hippocampus and frontal cortex of a prenatal stress model of depression (Detka et al, 2014). This higher glucose concentration may result from the intensification of brain glucose uptake or a weakening of glucose metabolism.…”

“…Additionally changes induced by prenatal stress appear gradually and are present in adult animals, which allows for the determination of progressive responses to adverse factors. Our previous studies using this model showed also more potent glucocorticoid action in the brain (connected with changes in factors that regulate glucocorticoid receptor function), increased concentrations of glucose, glycogen, glucose transporters and corticosterone in the brain, and insulin resistance (Szymańska et al, 2009a(Szymańska et al, , 2009bBudziszewska et al, 2010;Detka et al, 2014).…”

“…For example, the Flinders Sensitive Line rat, a well-validated model of depression, exhibits increased glucose utilization in brain structures important in the pathogenesis of depression (Kanemaru and Diksic, 2009). Additionally, our previous studies demonstrated that glucose, glycogen and glucose transporter (GLUT-1 and GLUT-4) concentrations are higher in the hippocampus and frontal cortex in prenatally stressed rats when compared with control animals (Detka et al, 2014). These data and the results obtained with Flinders Sensitive Line rats indicate that brain metabolic changes in animal models of depression are complex and various stages of glucose metabolism (uptake, glycolysis, the Krebs cycle, and oxidative phosphorylation) in particular brain regions can be differentially disturbed.…”

“…In addition, glucose-6-phosphate dehydrogenase was examined because glucose metabolism in the pentose cycle is a major source of NADPH that can be used to remove excess of reactive oxygen species while oxidative stress plays a role in the pathogenesis of depression. Previously observed changes in glucose, glycogen and glucose transporters were stronger after exposure of prenatally stressed rats to adverse factors (acute stress, glucose load) in adulthood (Detka et al, 2014). For the current study, we assessed the concentrations of selected markers involved in glucose metabolism at basal conditions and in animals subjected to stress or administered glucose as adults.…”