How Oxidative Stress Induces Depression?

Area of Science:

• Neuroscience
• Biochemistry
• Psychiatry

Background:

• Depression is a global health issue with complex pathogenesis.
• Current antidepressants targeting monoamine systems have limitations like slow onset and treatment resistance.
• Novel antidepressants like esketamine target the glutamatergic system but have side effects.

Purpose of the Study:

• To explore novel depression pathogenesis involving oxidative stress (OS).
• To elucidate the downstream pathways of OS-induced depression.
• To identify new therapeutic targets for safer and more effective depression treatments.

Main Methods:

• Review of accumulating clinical and animal studies.
• Summary and exposition of OS downstream pathways.
• Elaboration on molecular mechanisms and interactions between pathways.

Main Results:

• Oxidative stress is critically involved in depression.
• Key downstream pathways include mitochondrial impairment, neuroinflammation, glutamate excitotoxicity, BDNF/TrkB dysfunction, serotonin deficiency, microbiota-gut-brain axis, and HPA axis dysregulation.
• Intricate interactions and molecular mechanisms mediating these pathways were analyzed.

Conclusions:

• Oxidative stress is a significant factor in depression.
• Understanding OS-induced pathways provides insights into depression mechanisms.
• This review offers potential novel targets for developing more effective and safer depression therapies.