Antioxidant carbon dot nanozymes alleviate depression in rats by restoring the gut microbiome

Depression is a significant challenge to diagnose and treat. Among the factors influencing depression onset and severity, there is growing evidence for chemical imbalances that generate oxidative stress throughout the body. To address this problem, researchers reporting in the journal Langmuir have developed antioxidant carbon dot nanozymes (synthetic enzyme-like substances) that reduced oxidative stress, rebalanced gut microbes and alleviated stress-induced depression in rats.

Mental health disorders such as depression not only reduce the quality of life for affected individuals, but also challenge public health and economic prosperity. One of the potential hallmarks of depressive disorder is a buildup of reactive oxygen- and nitrogen-containing compounds, which can overwhelm the body’s natural defenses. The resulting oxidative stress impacts gut health by disrupting the balance of microbes, which can trigger inflammation and alter brain and neuronal function.

To correct this problem, Jihong Huang, Weiwei He and colleagues synthesized enzyme-like substances with a strong antioxidant capacity to reduce the reactive species and thereby restore gut microbe balance and alleviate depression.

The researchers created carbon dot nanozymes (CDzymes) by polymerizing glucose and the amino acid histidine to ensure antioxidant activity while maintaining biocompatibility. The CDzymes neutralized a range of reactive species in solution and in cultured mouse nerve cells without signs of toxicity.

The researchers then moved to a rat model of depression known as chronic and unpredictable mild stress (CUMS). They compared animals in four groups—healthy rats, untreated CUMS rats, and CUMS rats treated with either gamma-aminobutyric acid (GABA), an antidepressant drug that inhibits nerve signaling, or CDzymes.

Rats receiving either treatment displayed less depressive behavior than untreated CUMS rats in terms of reward-seeking, curiosity, willingness to explore and resistance to despair. The behavioral improvements observed with GABA or CDzymes treatment also aligned with improved levels of several depression-related neurotransmitters isolated from brain tissues.

The researchers then explored the impact of CUMS and treatment on the rodents’ gut microbiome by analyzing fecal microbes. Although microbial richness and diversity was greatly reduced in the depressed animals, this reduction was largely reversed to the same degree with GABA or CDzymes treatment.

Additionally, the types of microbes present in the feces of treated rats were much closer to that of healthy rats, highlighting the link between gut health and mental health. This microbial restoration also resulted in improved metabolism of several amino acids critical to nerve signaling.

Taken together, these results present CDzymes as effective as GABA in animal studies, making it another potential therapeutic option for addressing depressive disorder.