School of Nursing, University of Pennsylvania, 418 Curie Boulevard, Philadelphia, PA 19104, USA.
Physiol Behav. 2012 Feb 1;105(3):702-8. doi: 10.1016/j.physbeh.2011.09.003. Epub 2011 Sep 10.
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.
临床研究表明，糖尿病和抑郁症之间存在双向关系，糖尿病可能会增加抑郁症状的风险，而抑郁症可能会增加患糖尿病的风险。研究糖尿病对大脑和行为影响的临床前模型可以为这种关系的病理生理学提供深入了解。本研究在 C57BL/6 小鼠中全面检查了由链脲佐菌素 (STZ) 诱导的糖尿病引起的抑郁表型的发展，并确定胰岛素治疗是否能够逆转与糖尿病相关的大脑和情感行为变化。由于焦虑常常与情绪障碍并存，因此对焦虑和抑郁的行为测试都进行了测试。还测量了可能与行为变化相关的生理指标，包括海马细胞增殖、脑源性神经营养因子和血浆皮质酮。STZ 诱导的糖尿病导致悬尾试验中不动性增加、颅内自我刺激阈值升高、海马细胞增殖减少和皮质酮水平升高。另一方面，胰岛素治疗可降低高血糖，逆转行为效应，并使海马细胞增殖和皮质酮水平恢复到与对照组相当的水平。焦虑相关行为不受影响。这项研究表明，在小鼠中进行的实验性糖尿病产生了抑郁表型，这些表型可以通过胰岛素治疗来逆转。与奖赏相关的行为和海马细胞增殖的变化可能是识别治疗糖尿病和抑郁症合并症的治疗干预措施的有用标志物。
