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

Depression is a major challenge to diagnose and treat. Among the factors that influence the onset and severity of depression, there is growing evidence of chemical imbalances that produce oxidative stress throughout the body. To address this issue, researchers Report In the journal Langmuir We developed an antioxidant carbon dot nanozyme (a synthetic enzyme-like substance) that reduced oxidative stress, balanced gut bacteria, and alleviated stress-induced depression in rats.

Mental illnesses such as depression not only reduce the quality of life of affected individuals, but also have adverse effects on public health and economic prosperity. One of the underlying hallmarks of depression is the accumulation of reactive oxygen and nitrogen-containing compounds, which can overwhelm the body’s natural defenses. The resulting oxidative stress can disrupt microbial balance, affect gut health, cause inflammation, and alter brain and neuronal function.

To solve this problem, Jihong Huang, Weiwei He and colleagues synthesized an enzyme-like substance with strong antioxidant ability, which could reduce reactive species and restore the balance of gut bacteria, thus alleviating depression.

To ensure antioxidant activity while maintaining biocompatibility, the researchers polymerized glucose and the amino acid histidine to create carbon dot nanozymes (CDzymes), which neutralized a range of reactive species in solution and in cultured mouse neuronal cells without any signs of toxicity.

The researchers next moved on to a rat model of depression known as chronic unpredictable mild stress (CUMS). They compared four groups of animals: healthy rats, untreated CUMS rats, and CUMS rats that were given either gamma-aminobutyric acid (GABA), an antidepressant that blocks nerve signaling, or CDzymes.

Rats receiving either treatment showed 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 were also consistent with improved levels of several depression-related neurotransmitters isolated from brain tissue.

The researchers then investigated the impact of CUMS and treatment on the rodents’ gut microbiome by analyzing fecal microbes. Depressed animals experienced a significant decrease in microbial richness and diversity, while GABA or CDzymes treatment largely restored this decrease to a similar extent.

Moreover, the microbial populations present in the faeces of treated rats were very similar to those of healthy rats, highlighting a link between gut health and mental health. Restoration of this microbiome also improved the metabolism of several amino acids important for neuronal signaling.

Taken together, these results indicate that CDzyme has similar effects to GABA in animal studies and may represent a new therapeutic option for addressing depression.