Low Blood Sodium Levels Disrupt Brain Function, Leading to Anxiety
A study shows that chronic hyponatremia disrupts neurotransmitter function in the brain, leading to anxiety in mice.
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A recent study led by Professor Yoshihisa Sugimura and colleagues at Fujita Health University, Japan, has uncovered a direct link between chronic hyponatremia (CHN) and anxiety-like behaviors in mice. Published in Molecular Neurobiology on May 14, 2025, the research suggests that low blood sodium levels disrupt neurotransmitter function in the brain, particularly in the amygdala, a region involved in emotional regulation.
Chronic hyponatremia (CHN)
A long-term condition where blood sodium levels remain abnormally low, often resulting from conditions like heart failure, liver cirrhosis or SIAD. This imbalance can affect various physiological processes, including brain function.Amygdala
A region of the brain involved in processing emotions, including fear and anxiety. It plays a critical role in regulating emotional responses and is often studied in relation to mood disorders.Hyponatremia and its neurological effects
Hyponatremia, characterized by low sodium levels in the blood, is often seen in patients with conditions like liver cirrhosis, heart failure or syndrome of inappropriate antidiuresis (SIAD). While the condition is traditionally viewed as symptomless, recent findings indicate that CHN can lead to significant neurological consequences, including anxiety-like behaviors. This study provides evidence that chronic low sodium levels may disrupt key neurotransmitter systems, leading to altered emotional responses.How chronic hyponatremia was studied
To investigate the effects of CHN on behavior, the researchers developed a mouse model mimicking the low-sodium environment seen in chronic hyponatremia by using desmopressin, a vasopressin analog, and feeding the animals a liquid diet. The mice displayed significantly reduced serum sodium levels over an extended period, which mirrored chronic hyponatremia in humans. Behavioral tests, including the light/dark transition and open field tests, revealed that the mice exhibited increased anxiety-like behaviors.“While CHN has been associated with cognitive impairments, our study is among the first to provide evidence that it also leads to innate anxiety-like behaviors through changes in brain chemistry."
Dr. Haruki Fujisawa.
Neurotransmitter changes in the amygdala
Further biochemical analysis of the mice's brains showed a reduction in serotonin and dopamine levels in the amygdala, both of which are essential for mood regulation. The study also found decreased phosphorylation of extracellular signal-regulated kinase (ERK), a key molecular signal associated with emotional regulation. These findings suggest that CHN disrupts the balance of neurotransmitters in the amygdala, leading to heightened anxiety-like behaviors.
Extracellular signal-regulated kinase (ERK)
A protein that is involved in the regulation of cellular functions, including those related to emotion and memory. ERK phosphorylation is an important signaling mechanism in the brain that affects emotional responses.Reversal of anxiety-like behaviors
The researchers then tested whether correcting the sodium imbalance could reverse the anxiety-like behaviors. After stopping the desmopressin infusion and reverting the mice to a solid diet, their sodium levels returned to normal. This resulted in a reduction of anxiety-like behaviors and a return to normal levels of serotonin, dopamine and ERK phosphorylation in the amygdala. This suggests that the effects of CHN on anxiety could be reversible with proper treatment of sodium imbalance.
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Implications for human health
Although the study was conducted in mice, the findings have potential relevance for humans, particularly the elderly and individuals with chronic illnesses, who are more susceptible to hyponatremia. Chronic hyponatremia has long been recognized as a metabolic condition, but this study highlights its neurological and psychological consequences. Early detection and treatment of CHN could not only prevent physical harm but also improve the mental well-being of affected individuals.
This study emphasizes the importance of recognizing chronic hyponatremia as more than just a metabolic disorder, but also a condition that can significantly impact brain function and mental health. By improving diagnosis and treatment of CHN, there is potential to enhance the quality of life for individuals suffering from this condition.
Reference: Fujisawa H, Magara N, Nakayama S, et al. Chronic hyponatremia potentiates innate anxiety-like behaviors through the dysfunction of monoaminergic neurons in mice. Mol Neurobiol. 2025. doi: 10.1007/s12035-025-05024-y
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