Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia

Takeshi Y. Hiyama, Shinichi Matsuda, Akihiro Fujikawa, Masahito Matsumoto, Eiji Watanabe, Hiroshi Kajiwara, Fumio Niimura, Masaharu Noda

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Nax is the sodium-level sensor of body fluids in the brain involved in sodium homeostasis. Nax-knockout mice do not stop ingesting salt even when dehydrated. Here we report a case with clinical features of essential hypernatremia without demonstrable hypothalamic structural lesions, who was diagnosed as a paraneoplastic neurologic disorder. The patient had autoantibodies directed against Nax, along with a ganglioneuroma composed of Schwann-like cells robustly expressing Nax. The removal of the tumor did not reduce the autoantibody levels or relieve the symptoms. Intravenous injection of the immunoglobulin fraction of the patient's serum into mice induced abnormalities in water/salt intake and diuresis, which led to hypernatremia. In the brains of these mice, cell death was observed along with focal deposits of complement C3 and inflammatory infiltrates in circumventricular organs where Nax is specifically expressed. Our findings thus provide new insights into the pathogenesis of hypernatremia relevant to the sodium-level-sensing mechanism in humans.

Original languageEnglish
Pages (from-to)508-522
Number of pages15
JournalNeuron
Volume66
Issue number4
DOIs
Publication statusPublished - May 1 2010
Externally publishedYes

Fingerprint

Hypernatremia
Autoimmunity
Sodium
Autoantibodies
Brain
Salts
Ganglioneuroma
Complement C3
Diuresis
Intravenous Immunoglobulins
Schwann Cells
Body Fluids
Nervous System Diseases
Knockout Mice
Intravenous Injections
Drinking
Homeostasis
Cell Death
Serum
Neoplasms

Keywords

  • Cellimmuno
  • Humdisease
  • Molneuro

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hiyama, T. Y., Matsuda, S., Fujikawa, A., Matsumoto, M., Watanabe, E., Kajiwara, H., ... Noda, M. (2010). Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia. Neuron, 66(4), 508-522. https://doi.org/10.1016/j.neuron.2010.04.017

Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia. / Hiyama, Takeshi Y.; Matsuda, Shinichi; Fujikawa, Akihiro; Matsumoto, Masahito; Watanabe, Eiji; Kajiwara, Hiroshi; Niimura, Fumio; Noda, Masaharu.

In: Neuron, Vol. 66, No. 4, 01.05.2010, p. 508-522.

Research output: Contribution to journalArticle

Hiyama, TY, Matsuda, S, Fujikawa, A, Matsumoto, M, Watanabe, E, Kajiwara, H, Niimura, F & Noda, M 2010, 'Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia', Neuron, vol. 66, no. 4, pp. 508-522. https://doi.org/10.1016/j.neuron.2010.04.017
Hiyama TY, Matsuda S, Fujikawa A, Matsumoto M, Watanabe E, Kajiwara H et al. Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia. Neuron. 2010 May 1;66(4):508-522. https://doi.org/10.1016/j.neuron.2010.04.017
Hiyama, Takeshi Y. ; Matsuda, Shinichi ; Fujikawa, Akihiro ; Matsumoto, Masahito ; Watanabe, Eiji ; Kajiwara, Hiroshi ; Niimura, Fumio ; Noda, Masaharu. / Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia. In: Neuron. 2010 ; Vol. 66, No. 4. pp. 508-522.
@article{7ef25a5277cd4cc2bf5cd9141d059e21,
title = "Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia",
abstract = "Nax is the sodium-level sensor of body fluids in the brain involved in sodium homeostasis. Nax-knockout mice do not stop ingesting salt even when dehydrated. Here we report a case with clinical features of essential hypernatremia without demonstrable hypothalamic structural lesions, who was diagnosed as a paraneoplastic neurologic disorder. The patient had autoantibodies directed against Nax, along with a ganglioneuroma composed of Schwann-like cells robustly expressing Nax. The removal of the tumor did not reduce the autoantibody levels or relieve the symptoms. Intravenous injection of the immunoglobulin fraction of the patient's serum into mice induced abnormalities in water/salt intake and diuresis, which led to hypernatremia. In the brains of these mice, cell death was observed along with focal deposits of complement C3 and inflammatory infiltrates in circumventricular organs where Nax is specifically expressed. Our findings thus provide new insights into the pathogenesis of hypernatremia relevant to the sodium-level-sensing mechanism in humans.",
keywords = "Cellimmuno, Humdisease, Molneuro",
author = "Hiyama, {Takeshi Y.} and Shinichi Matsuda and Akihiro Fujikawa and Masahito Matsumoto and Eiji Watanabe and Hiroshi Kajiwara and Fumio Niimura and Masaharu Noda",
year = "2010",
month = "5",
day = "1",
doi = "10.1016/j.neuron.2010.04.017",
language = "English",
volume = "66",
pages = "508--522",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia

AU - Hiyama, Takeshi Y.

AU - Matsuda, Shinichi

AU - Fujikawa, Akihiro

AU - Matsumoto, Masahito

AU - Watanabe, Eiji

AU - Kajiwara, Hiroshi

AU - Niimura, Fumio

AU - Noda, Masaharu

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Nax is the sodium-level sensor of body fluids in the brain involved in sodium homeostasis. Nax-knockout mice do not stop ingesting salt even when dehydrated. Here we report a case with clinical features of essential hypernatremia without demonstrable hypothalamic structural lesions, who was diagnosed as a paraneoplastic neurologic disorder. The patient had autoantibodies directed against Nax, along with a ganglioneuroma composed of Schwann-like cells robustly expressing Nax. The removal of the tumor did not reduce the autoantibody levels or relieve the symptoms. Intravenous injection of the immunoglobulin fraction of the patient's serum into mice induced abnormalities in water/salt intake and diuresis, which led to hypernatremia. In the brains of these mice, cell death was observed along with focal deposits of complement C3 and inflammatory infiltrates in circumventricular organs where Nax is specifically expressed. Our findings thus provide new insights into the pathogenesis of hypernatremia relevant to the sodium-level-sensing mechanism in humans.

AB - Nax is the sodium-level sensor of body fluids in the brain involved in sodium homeostasis. Nax-knockout mice do not stop ingesting salt even when dehydrated. Here we report a case with clinical features of essential hypernatremia without demonstrable hypothalamic structural lesions, who was diagnosed as a paraneoplastic neurologic disorder. The patient had autoantibodies directed against Nax, along with a ganglioneuroma composed of Schwann-like cells robustly expressing Nax. The removal of the tumor did not reduce the autoantibody levels or relieve the symptoms. Intravenous injection of the immunoglobulin fraction of the patient's serum into mice induced abnormalities in water/salt intake and diuresis, which led to hypernatremia. In the brains of these mice, cell death was observed along with focal deposits of complement C3 and inflammatory infiltrates in circumventricular organs where Nax is specifically expressed. Our findings thus provide new insights into the pathogenesis of hypernatremia relevant to the sodium-level-sensing mechanism in humans.

KW - Cellimmuno

KW - Humdisease

KW - Molneuro

UR - http://www.scopus.com/inward/record.url?scp=77953263987&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953263987&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2010.04.017

DO - 10.1016/j.neuron.2010.04.017

M3 - Article

C2 - 20510856

AN - SCOPUS:77953263987

VL - 66

SP - 508

EP - 522

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 4

ER -