Hyponatremia, a condition characterized by low blood sodium levels, has long been considered symptomless. However, recent research led by Professor Yoshihisa Sugimura and his team from Fujita Health University in Japan has revealed that chronic hyponatremia (CHN) can lead to anxiety-like behaviors in mice by disrupting key neurotransmitters in the brain. Their study, published in the journal Molecular Neurobiology, highlights the impact of CHN on monoaminergic signaling in the amygdala, a region of the brain crucial for processing emotions and fear.

Dr. Haruki Fujisawa explains, "While cognitive impairments have been linked to CHN, our research is one of the first to demonstrate that it can also result in innate anxiety-like behaviors due to alterations in brain chemistry."

Hyponatremia is commonly associated with conditions such as liver cirrhosis, heart failure, or syndrome of inappropriate antidiuresis (SIAD). In chronic cases, the brain adapts to the low-sodium environment through a compensatory mechanism called volume regulatory decrease (VRD). However, this adaptation comes with a physiological cost.

The compensatory process involves the loss of organic osmolytes and neurotransmitter precursors that help maintain brain cell volume under low-sodium conditions. This loss may disrupt the production, release, or recycling of essential mood-regulating chemicals over time.

To investigate the neurological effects of CHN, the researchers developed a mouse model using desmopressin infusion and a liquid diet to mimic SIAD. The mice showed significantly lower serum sodium levels, consistent with CHN, and displayed increased anxiety-like behaviors in standard neuroscience behavioral tests.

Further analysis revealed reduced levels of serotonin and dopamine, key neurotransmitters involved in mood regulation, in the amygdala of mice with CHN. These changes were accompanied by decreased extracellular signal-regulated kinase (ERK) phosphorylation, a molecular signal associated with emotional regulation.

Prof. Sugimura notes, "Our findings indicate that CHN disrupts the balance of monoamines, particularly serotonin and dopamine, in the amygdala, influencing innate anxiety." When the researchers corrected the mice's sodium levels, the anxiety-like behaviors diminished, and neurotransmitter levels returned to normal.

While the study focused on mice, the implications could extend to humans, especially elderly individuals and those with chronic illnesses who are prone to CHN. Recognizing and addressing the neurological effects of CHN can enhance the quality of life for affected individuals.

Prof. Sugimura emphasizes, "Chronic hyponatremia is not merely a metabolic abnormality but a condition with significant neurological and psychological implications. Early diagnosis and treatment are crucial not only for brain health but also for mental well-being."