Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress
Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress
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DOI：
10.1073/pnas.97.20.11056
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发表时间：
2000-09-26
影响因子：
11.1
通讯作者：
McEwen, BS
中科院分区：
文献类型：
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作者：
Magariños, AM;McEwen, BS
我们报告说，链脲佐菌素 (STZ) 诱导大鼠 9 天不受控制的实验性糖尿病是一种内源性慢性应激源，会导致海马 CA3 锥体神经元顶端树突收缩和简化，在非糖尿病大鼠中经过 21 天的重复束缚应激或慢性皮质酮 (Cort) 治疗后也观察到这种效应。糖尿病还会引起突触前苔藓纤维末端 (MFT) 的形态变化，从而与近端 CA3 顶端树突形成兴奋性突触接触。一种效应是突触小泡耗竭，发生在糖尿病中以及反复应激和 Cort 治疗后。然而，糖尿病产生了其他 MFT 结构变化，这些变化在质量和数量上都与其他治疗方法不同。此外，虽然 7 天的重复应激不足以在非糖尿病大鼠中产生树突或突触重塑，但它会增强 STZ 大鼠的树突萎缩和 MFT 突触小泡耗竭。这些变化与肾上腺肥大、基础 Cort 释放升高以及应激后 Cort 分泌的过敏和关闭缺陷同时发生。因此，作为一种内源性应激源。 STZ 糖尿病不仅会加速外源性应激的影响，从而改变海马形态；它还会产生与非糖尿病状态下压力和 Cort 产生的结构变化仅部分重叠的结构变化。
We report that 9 d of uncontrolled experimental diabetes induced by streptozotocin (STZ) in rats is an endogenous chronic stressor that produces retraction and simplification of apical dendrites of hippocampal CA3 pyramidal neurons, an effect also observed in nondiabetic rats after 21 d of repeated restraint stress or chronic corticosterone (Cort) treatment. Diabetes also induces morphological changes in the presynaptic mossy fiber terminals (MFT) that form excitatory synaptic contacts with the proximal CA3 apical dendrites. One effect, synaptic vesicle depletion, occurs in diabetes as well as after repeated stress and Cort treatment. However, diabetes produced other MFT structural changes that differ qualitatively and quantitatively from other treatments. Furthermore, whereas 7 d of repeated stress was insufficient to produce dendritic or synaptic remodeling in nondiabetic rats, it potentiated both dendritic atrophy and MFT synaptic vesicle depletion in STZ rats. These changes occurred in concert with adrenal hypertrophy and elevated basal Cort release as well as hypersensitivity and defective shutoff of Cort secretion after stress. Thus, as an endogenous stressor. STZ diabetes not only accelerates the effects of exogenous stress to alter hippocampal morphology; it also produces structural changes that overlap only partially with those produced by stress and Cort in the nondiabetic state.