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 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.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan;
authors.forename: Haruki
authors.initials: H
authors.lastname: Fujisawa
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan; sugiyosi@med.nagoya-u.ac.jp.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Sugimura
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan;
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takagi
authors.affiliation: Futuristic Environmental Simulation Center, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan;
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizoguchi
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan;
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan;
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Izumida
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan;
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Nakashima
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan;
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ochiai
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan;
authors.forename: Seiji
authors.initials: S
authors.lastname: Takeuchi
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan;
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kiyota
authors.affiliation: Futuristic Environmental Simulation Center, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan;
authors.forename: Kazuya
authors.initials: K
authors.lastname: Fukumoto
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan; Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan;
authors.forename: Shintaro
authors.initials: S
authors.lastname: Iwama
authors.affiliation: Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; and.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Takagishi
authors.affiliation: Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; and.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan;
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arima
authors.affiliation: Department of Neuroscience, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Komatsu
authors.affiliation: Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan; and.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Murata
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan;
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000503:physiopathology; D056654:CA3 Region, Hippocampal / Q000503:physiopathology; D002478:Cells, Cultured; D002908:Chronic Disease; D003072:Cognition Disorders / Q000097:blood / Q000209:etiology; D004195:Disease Models, Animal; D005239:Fear / Q000502:physiology; D020233:Gait Disorders, Neurologic / Q000097:blood / Q000209:etiology*; D018698:Glutamic Acid / Q000378:metabolism; D007010:Hyponatremia / Q000097:blood / Q000150:complications* / Q000523:psychology; D007177:Inappropriate ADH Syndrome / Q000150:complications / Q000503:physiopathology* / Q000523:psychology; D008297:Male; D008569:Memory Disorders / Q000097:blood / Q000209:etiology*; D017551:Microdialysis; D009473:Neuronal Plasticity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000097:blood / Q000494:pharmacology; D013569:Synapses / Q000502:physiology
chemical_list: D018698:Glutamic Acid; D012964:Sodium
keywords: dementia; electrolytes; hyponatremia; osmolality; vasopressin; water-electrolyte balance