Diabetes as a chronic metabolic stressor: causes, consequences and clinical complications

Abstract

Diabetes mellitus is an endocrine disorder resulting from inadequate insulin release and/or reduced insulin sensitivity. The complications of diabetes are well characterized in peripheral tissues, but there is a growing appreciation that the complications of diabetes extend to the central nervous system (CNS). One of the potential neurological complications of diabetes is cognitive deficits. Interestingly, the structural, electrophysiological, neurochemical and anatomical underpinnings responsible for cognitive deficits in diabetes are strikingly similar to those observed in animals subjected to chronic stress, as well as in patients with stress-related psychiatric illnesses such as major depressive disorder. Since diabetes is a chronic metabolic stressor, this has led to the suggestion that common mechanistic mediators are responsible for neuroplasticity deficits in both diabetes and depression. Moreover, these common mechanistic mediators may be responsible for the increase in the risk of depressive illness in diabetes patients. In view of these observations, the aims of this review are (1) to describe the neuroplasticity deficits observed in diabetic rodents and patients; (2) to summarize the similarities in the clinical and preclinical studies of depression and diabetes; and (3) to highlight the diabetes-induced neuroplasticity deficits in those brain regions that have been implicated as important pathological centers in depressive illness, namely, the hippocampus, the amygdala and the prefrontal cortex.

Copyright © 2011 Elsevier Inc. All rights reserved.

Figures

Figure 1

Diabetes-induced changes in neuroplasticity in the hippocampus, amygdala and prefrontal cortex in animal models. T1DM and T2DM rodents exhibit deficits in neuroplasticity in the prefrontal cortex (blue), hippocampus (red) or the amygdala (green). Neuroplasticity deficits may include electrophysiological deficits such as impairments in LTP, neuroanatomical alterations such as changes in dendritic morphology or neuronal spine density and alterations in neurochemical profiles. Ultimately, these changes may contribute to the development of cognitive-behavioral deficits diabetic animals. See text for details. Figure adapted from (Reznikov et al., 2009).

Figure 2

Potential neurological causes and complications that link diabetes and depressive illness. A variety of neuroplasticity deficits may provide links in the chain that couple diabetes and depression, thereby increasing the risk of co-morbid depressive illness in diabetes patients. See text for details.