Chronic hyponatremia causes neurologic and psychologic impairments

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 cancermay 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.

Original languageEnglish
Pages (from-to)766-780
Number of pages15
JournalJournal of the American Society of Nephrology
Volume27
Issue number3
DOIs
Publication statusPublished - 03-2016

Fingerprint

Hyponatremia
Gait
Nervous System
Long-Term Potentiation
Glutamic Acid
Sodium
Quality of Life
Ions
Inappropriate ADH Syndrome
Adrenal Insufficiency
Mortality
Microdialysis
Brain
Neurologic Manifestations
Astrocytes
Liver Cirrhosis
Synapses
Electrolytes
Fear
Hippocampus

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Fujisawa, H., Sugimura, Y., Takagi, H., Mizoguchi, H., Takeuchi, H., Izumida, H., ... Oiso, Y. (2016). Chronic hyponatremia causes neurologic and psychologic impairments. Journal of the American Society of Nephrology, 27(3), 766-780. https://doi.org/10.1681/ASN.2014121196
Fujisawa, Haruki ; Sugimura, Yoshihisa ; Takagi, Hiroshi ; Mizoguchi, Hiroyuki ; Takeuchi, Hideyuki ; Izumida, Hisakazu ; Nakashima, Kohtaro ; Ochiai, Hiroshi ; Takeuchi, Seiji ; Kiyota, Atsushi ; Fukumoto, Kazuya ; Iwama, Shintaro ; Takagishi, Yoshiko ; Hayashi, Yoshitaka ; Arima, Hiroshi ; Komatsu, Yukio ; Murata, Yoshiharu ; Oiso, Yutaka. / Chronic hyponatremia causes neurologic and psychologic impairments. In: Journal of the American Society of Nephrology. 2016 ; Vol. 27, No. 3. pp. 766-780.
@article{cba213701d4b473ebb70f5093f3ec557,
title = "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 cancermay 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.",
author = "Haruki Fujisawa and Yoshihisa Sugimura and Hiroshi Takagi and Hiroyuki Mizoguchi and Hideyuki Takeuchi and Hisakazu Izumida and Kohtaro Nakashima and Hiroshi Ochiai and Seiji Takeuchi and Atsushi Kiyota and Kazuya Fukumoto and Shintaro Iwama and Yoshiko Takagishi and Yoshitaka Hayashi and Hiroshi Arima and Yukio Komatsu and Yoshiharu Murata and Yutaka Oiso",
year = "2016",
month = "3",
doi = "10.1681/ASN.2014121196",
language = "English",
volume = "27",
pages = "766--780",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "3",

}

Fujisawa, H, Sugimura, Y, Takagi, H, Mizoguchi, H, Takeuchi, H, Izumida, H, Nakashima, K, Ochiai, H, Takeuchi, S, Kiyota, A, Fukumoto, K, Iwama, S, Takagishi, Y, Hayashi, Y, Arima, H, Komatsu, Y, Murata, Y & Oiso, Y 2016, 'Chronic hyponatremia causes neurologic and psychologic impairments', Journal of the American Society of Nephrology, vol. 27, no. 3, pp. 766-780. https://doi.org/10.1681/ASN.2014121196

Chronic hyponatremia causes neurologic and psychologic impairments. / Fujisawa, Haruki; Sugimura, Yoshihisa; Takagi, Hiroshi; Mizoguchi, Hiroyuki; Takeuchi, Hideyuki; Izumida, Hisakazu; Nakashima, Kohtaro; Ochiai, Hiroshi; Takeuchi, Seiji; Kiyota, Atsushi; Fukumoto, Kazuya; Iwama, Shintaro; Takagishi, Yoshiko; Hayashi, Yoshitaka; Arima, Hiroshi; Komatsu, Yukio; Murata, Yoshiharu; Oiso, Yutaka.

In: Journal of the American Society of Nephrology, Vol. 27, No. 3, 03.2016, p. 766-780.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Chronic hyponatremia causes neurologic and psychologic impairments

AU - Fujisawa, Haruki

AU - Sugimura, Yoshihisa

AU - Takagi, Hiroshi

AU - Mizoguchi, Hiroyuki

AU - Takeuchi, Hideyuki

AU - Izumida, Hisakazu

AU - Nakashima, Kohtaro

AU - Ochiai, Hiroshi

AU - Takeuchi, Seiji

AU - Kiyota, Atsushi

AU - Fukumoto, Kazuya

AU - Iwama, Shintaro

AU - Takagishi, Yoshiko

AU - Hayashi, Yoshitaka

AU - Arima, Hiroshi

AU - Komatsu, Yukio

AU - Murata, Yoshiharu

AU - Oiso, Yutaka

PY - 2016/3

Y1 - 2016/3

N2 - 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 cancermay 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.

AB - 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 cancermay 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.

UR - http://www.scopus.com/inward/record.url?scp=84959877886&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959877886&partnerID=8YFLogxK

U2 - 10.1681/ASN.2014121196

DO - 10.1681/ASN.2014121196

M3 - Article

C2 - 26376860

AN - SCOPUS:84959877886

VL - 27

SP - 766

EP - 780

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 3

ER -