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 language | English |
|---|---|
| Pages (from-to) | 766-780 |
| Number of pages | 15 |
| Journal | Journal of the American Society of Nephrology |
| Volume | 27 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 03-2016 |
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All Science Journal Classification (ASJC) codes
- Nephrology
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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 journal › Article
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 -