Chronic Hyponatremia Causes Neurologic and Psychologic Impairments
Chronic Hyponatremia Causes Neurologic and Psychologic Impairments
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DOI：
10.1681/asn.2014121196
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发表时间：
2016-03-01
影响因子：
13.6
通讯作者：
Oiso, Yutaka
中科院分区：
文献类型：
--
作者：
Fujisawa, Haruki;Sugimura, Yoshihisa;Oiso, Yutaka
低钠血症是临床上最常见的电解质紊乱。慢性低钠血症曾被认为是对大脑适应的无症状反应，但最近的证据表明，慢性低钠血症可能与注意力缺陷、步态障碍、福尔斯风险和认知障碍有关。这种神经缺陷与生活质量的降低有关，可能是死亡的重要原因。然而，由于基础疾病如肾上腺功能不全、心力衰竭、肝硬化和癌症也可能影响脑功能，因此低钠血症单独对神经系统表现的贡献及其潜在机制仍不清楚。使用抗利尿激素分泌不当综合征大鼠模型，我们在这里表明，持续降低血清钠离子浓度诱导步态障碍;促进灭绝的上下文恐惧记忆;造成认知障碍，在一个新的物体识别测试;和受损的长时程增强海马CA 3-CA 1突触。在体内微透析揭示了慢性低钠血症大鼠海马细胞外谷氨酸浓度升高。持续的低细胞外钠离子浓度也降低了原代星形胶质细胞培养物对谷氨酸的摄取，证实了长时程增强受损的潜在机制。此外，纠正低钠血症大鼠的步态和记忆表现与对照组大鼠相当。因此，这些结果表明，人类慢性低钠血症可能导致步态障碍和认知障碍，但这些异常是可逆的，仔细纠正这种情况可能会改善生活质量并降低死亡率。
Hyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia may be linked to attention deficits, gait disturbances, risk of falls, and cognitive impairments. Such neurologic defects are associated with a reduction in quality of life and may be a significant cause of mortality. However, because underlying diseases such as adrenal insufficiency, heart failure, liver cirrhosis, and cancer may also affect brain function, the contribution of hyponatremia alone to neurologic manifestations and the underlying mechanisms remain unclear. Using a syndrome of inappropriate secretion of antidiuretic hormone rat model, we show here that sustained reduction of serum sodium ion concentration induced gait disturbances; facilitated the extinction of a contextual fear memory; caused cognitive impairment in a novel object recognition test; and impaired long-term potentiation at hippocampal CA3-CA1 synapses. In vivo microdialysis revealed an elevated extracellular glutamate concentration in the hippocampus of chronically hyponatremic rats. A sustained low extracellular sodium ion concentration also decreased glutamate uptake by primary astrocyte cultures, suggeiting an underlying mechanism of impaired long-term potentiation. Furthermore, gait and memory performances of corrected hyponatremic rats were equivalent to those of control rats. Thus, these results suggest chronic hyponatremia in humans may cause gait disturbance and cognitive impairment, but these abnormalities are reversible and careful correction of this condition may improve quality of life and reduce mortality.