Chronic Hyponatremia Causes Neurologic and Psychologic Impairments.

Abstract

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, suggesting 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.

• Authors: Haruki Fujisawa, Yoshihisa Sugimura, Hiroshi Takagi, Hiroyuki Mizoguchi, Hideyuki Takeuchi, Hisakazu Izumida, Kohtaro Nakashima, Hiroshi Ochiai, Seiji Takeuchi, Atsushi Kiyota, Kazuya Fukumoto, Shintaro Iwama, Yoshiko Takagishi, Yoshitaka Hayashi, Hiroshi Arima, Yukio Komatsu, Yoshiharu Murata, Yutaka Oiso
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 27 Issue 3 Pg. 766-80 (Mar 2016) ISSN: 1533-3450 [Electronic] United States
• PMID: 26376860 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 by the American Society of Nephrology.

Chemical References

• Glutamic Acid
• Sodium

Topics

• Animals
• Astrocytes (drug effects, metabolism)
• CA1 Region, Hippocampal (physiopathology)
• CA3 Region, Hippocampal (physiopathology)
• Cells, Cultured
• Chronic Disease
• Cognition Disorders (blood, etiology)
• Disease Models, Animal
• Fear (physiology)
• Gait Disorders, Neurologic (blood, etiology)
• Glutamic Acid (metabolism)
• Hyponatremia (blood, complications, psychology)
• Inappropriate ADH Syndrome (complications, physiopathology, psychology)
• Male
• Memory Disorders (blood, etiology)
• Microdialysis
• Neuronal Plasticity
• Rats
• Rats, Sprague-Dawley
• Sodium (blood, pharmacology)
• Synapses (physiology)