Psychology Department, Princeton University, Princeton, New Jersey, USA.
Synapse. 2010 Jul;64(7):528-32. doi: 10.1002/syn.20758.
In the hippocampus, glucocorticoids bind to two types of receptors: the mineralocorticoid receptor, which binds corticosterone with high affinity and is tonically occupied; and the glucocorticoid receptor, which is occupied during stress and at certain phases in the circadian cycle. Diabetes mellitus increases levels of glucocorticoids in both humans and animal models. To explore the contributions of hippocampal corticosteroid receptors to the diabetes-induced suppression of neuroplasticity, we manipulated these receptors in hippocampal slices from streptozocin-diabetic rats, a model of Type 1 diabetes mellitus. STZ-diabetes reduced long-term potentiation (LTP) at medial perforant path synapses in the dentate gyrus, and induced a bias in favor of long-term depression following intermediate stimulation frequencies. Bath application of the mineralocorticoid receptor agonist aldosterone restored LTP in slices from diabetic animals. These results suggest additional mechanisms for diabetes-induced functional alterations and support a restorative role for dentate gyrus mineralocorticoid receptors.
在海马体中，糖皮质激素与两种类型的受体结合：盐皮质激素受体，其与皮质酮具有高亲和力并且持续占据；以及糖皮质激素受体，其在应激期间和昼夜节律周期的某些阶段被占据。糖尿病会增加人类和动物模型中糖皮质激素的水平。为了探讨海马皮质甾醇受体对糖尿病引起的神经可塑性抑制的贡献，我们在链脲佐菌素诱导的糖尿病大鼠的海马切片中操纵了这些受体，这是 1 型糖尿病的模型。STZ 糖尿病降低了齿状回中内侧穿通路径突触的长时程增强（LTP），并在中等刺激频率后诱导了有利于长时程抑制的偏向。盐皮质激素受体激动剂醛固酮的浴应用恢复了糖尿病动物切片中的 LTP。这些结果为糖尿病引起的功能改变提供了其他机制，并支持齿状回盐皮质激素受体的恢复作用。
