Depressive phenotypes evoked by experimental diabetes are reversed by insulin

Abstract

Clinical studies suggest a bidirectional relationship between diabetes and depression, where diabetes may increase risk for depressive symptoms and depression may increase risk for diabetes. Preclinical models examining the effects of diabetes on brain and behavior can provide insights to the pathophysiology underlying this relationship. The current study comprehensively examined, in C57BL/6 mice, the development of depressive phenotypes evoked by diabetes induced by streptozotocin (STZ) and determined if insulin treatment was able to reverse the diabetes-related changes on brain and affective behavior. Since anxiety is often comorbid with mood disturbances, behavioral tests for both anxiety and depression were administered. Possible physiological correlates of behavioral changes, including hippocampal cell proliferation, brain derived neurotrophic factor, and plasma corticosterone, were also measured. STZ-induced diabetes resulted in increased immobility in the tail suspension test, increased intracranial self-stimulation thresholds, decreased hippocampal cell proliferation, and increased corticosterone levels. Insulin treatment, on the other hand, reduced hyperglycemia, reversed the behavioral effects, and returned hippocampal cell proliferation and corticosterone to levels comparable to the control group. Anxiety-related behaviors were unaffected. This study showed that experimental diabetes in the mouse produced depressive phenotypes that were reversed by insulin therapy. Changes in reward-related behaviors and hippocampal cell proliferation may be useful markers to identify therapeutic interventions for comorbid diabetes and depression.

Antidepressant-like and anxiolytic-like effects of hydrogen sulfide in streptozotocin-induced diabetic rats through inhibition of hippocampal oxidative stress

“…The TST and FST are widely used as robust assays for assessing the therapeutic effects of antidepressants (Fava, 2003;Fuchs and Fliugge, 2006;Castagne et al, 2011). In the present study, STZ-induced diabetic rats exhibited increased duration of immobility in TST and FST, which is consistent with previous reports (Miyata et al, 2005;Hirano et al, 2007;Ho et al, 2012;Chen et al, 2014). Importantly, administration of NaHS, a donor of H 2 S, reversed the diabetes-induced increase in the duration of immobility in TST, revealing an antidepressant-like effect of H 2 S in STZ-induced diabetes.…”

“…In rodent models of STZ-induced diabetes, depressive behaviors have been observed (Miyata et al, 2005;Hirano et al, 2007;Ho et al, 2012;Chen et al, 2014). The TST and FST are widely used as robust assays for assessing the therapeutic effects of antidepressants (Fava, 2003;Fuchs and Fliugge, 2006;Castagne et al, 2011).…”

Streptozotocin diabetic mice display depressive-like behavior and alterations in the structure, neurotransmission and plasticity of medial prefrontal cortex interneurons

“…In the present study we have also shown that the diabetic status induced in mice by streptozotocin (STZ), negatively influences the behavior in the tail suspension test (TST), resulting in a more prolonged duration of immobility. These results are also in accordance with those reported in other rodent models of this metabolic disorder (Gupta et al, 2014;Ho et al, 2012;Miyata et al, 2004).…”

Anti-depressant effect of hesperidin in diabetic rats

“…STZ-induced diabetes is a well-established animal model of type 1 diabetes that results in marked hyperglycaemia, probably through the destruction of pancreatic ␤-cells and lack of insulin secretion (Ho et al 2012).…”