Hyponatremia, or low blood sodium concentration, is usually considered a symptomless condition, but recent research reveals that chronic hyponatremia (CHN) can lead to anxiety-like behaviors in mice by affecting key neurotransmitters in the brain.
A team of researchers from Fujita Health University in Japan, led by Professor Yoshihisa Sugimura, found that CHN alters monoaminergic signaling in the amygdala, a brain region crucial for processing fear and emotion. The study, published in Molecular Neurobiology, sheds light on the impact of low sodium levels on brain chemistry.
Dr. Haruki Fujisawa explains, "While CHN has been linked to cognitive impairments, our study is one of the first to show that it can also result in innate anxiety-like behaviors due to changes 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 known as volume regulatory decrease (VRD), which can have physiological consequences.
This adaptation 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 sustained desmopressin infusion and a liquid diet to mimic SIAD. The mice showed 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 in mood regulation, in the amygdala of mice with CHN. These changes were accompanied by a decrease in extracellular signal-regulated kinase (ERK) phosphorylation, a molecular signal involved in emotional regulation.
Prof. Sugimura notes, "Our findings indicate that CHN disrupts the balance of monoamines, particularly serotonin and dopamine, in the amygdala, leading to altered anxiety responses."
When the researchers corrected the mice's sodium levels by stopping desmopressin infusion and switching to a solid diet, the anxiety-like behaviors subsided, and neurotransmitter levels returned to normal in the amygdala.
Dr. Fujisawa highlights, "This study demonstrates that CHN not only causes anxiety-like symptoms but also shows that these symptoms can be relieved by correcting sodium imbalances."
While the study focused on mice, the implications could extend to humans, especially elderly patients and those with chronic illnesses who are at risk of CHN. Early detection and treatment of its neurological effects could enhance their quality of life.
Prof. Sugimura concludes, "Our research emphasizes that chronic hyponatremia has significant neurological and psychological consequences, underscoring the importance of timely diagnosis and treatment for overall mental well-being."
Source: Medical Xpress
