Fujisawa Haruki, Magara Nobuhiko, Nakayama Shogo, Fuse Sachiho, Iwata Naoko, Hasegawa Masaya, Kubota Hisayoshi, Shoji Hirotaka, Hattori Satoko, Hagihara Hideo, Fujigaki Hidetsugu, Seino Yusuke, Mouri Akihiro, Miyakawa Tsuyoshi, Nabeshima Toshitaka, Suzuki Atsushi, Sugimura Yoshihisa
Department of Endocrinology, Diabetes and Metabolism, School of Medicine, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-Cho, Toyoake, Aichi, 470-1192, Japan.
Department of Endocrinology and Diabetes, Daido Hospital, Nagoya, Aichi, 457-8511, Japan.
Mol Neurobiol. 2025 May 14. doi: 10.1007/s12035-025-05024-y.
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 (CHN) may induce neurological manifestations, including psychological symptoms. However, the specific psychological symptoms induced by CHN, the mechanisms underlying these symptoms, and their potential reversibility remain unclear. Therefore, this study aimed to determine whether monoaminergic neurotransmission is associated with innate anxiety-like behaviors potentiated by CHN in a mouse model of CHN secondary to the syndrome of inappropriate antidiuresis. In the present study, using a mouse model of the syndrome of inappropriate antidiuresis presenting with CHN, we showed that the sustained reduction of serum sodium ion concentrations potentiated innate anxiety-like behaviors in the light/dark transition and open field tests. We also found that serotonin and dopamine levels in the amygdala were significantly lower in mice with CHN than in controls. Additionally, phosphorylation of extracellular signal-regulated kinase (ERK) in the amygdala was significantly reduced in mice with CHN. Notably, after correcting for CHN, the increased innate anxiety-like behaviors, decreased serotonin and dopamine levels, and reduced phosphorylation of ERK in the amygdala were normalized. These findings further underscore the importance of treating CHN and highlight potential therapeutic strategies for alleviating anxiety in patients with CHN, which will improve their quality of life.
低钠血症是最常见的临床电解质紊乱。曾经认为大脑适应后低钠血症是无症状的，但最近的证据表明，慢性低钠血症（CHN）可能会引发神经学表现，包括心理症状。然而，CHN引发的具体心理症状、这些症状背后的机制及其潜在的可逆性仍不清楚。因此，本研究旨在确定在抗利尿激素分泌失调综合征继发的CHN小鼠模型中，单胺能神经传递是否与CHN增强的先天性焦虑样行为有关。在本研究中，我们使用出现CHN的抗利尿激素分泌失调综合征小鼠模型，发现在明暗转换和旷场试验中，血清钠离子浓度的持续降低增强了先天性焦虑样行为。我们还发现，CHN小鼠杏仁核中的血清素和多巴胺水平显著低于对照组。此外，CHN小鼠杏仁核中细胞外信号调节激酶（ERK）的磷酸化水平显著降低。值得注意的是，纠正CHN后，杏仁核中增强的先天性焦虑样行为、降低的血清素和多巴胺水平以及降低的ERK磷酸化水平均恢复正常。这些发现进一步强调了治疗CHN的重要性，并突出了缓解CHN患者焦虑的潜在治疗策略，这将改善他们的生活质量。
