Oxidative Stress Induces Depression by Altering Central Glutamate Neurotransmission
Depression,a category of mental disorder characterized by core symptoms of anhedonia and depressed mood,seriously influences the physical and psychological health of people worldwide.Clinical and animal studies have been gradually revealing the complicated pathogenic mechanisms involved,and have proposed related hypothesis.The monoamine neurotransmitter deficiency theory has significantly contributed to the development and clinical application of the first-line antidepressants,however,the monoamine targeted drugs generally require more than two weeks of continuous drug treatment,and more-over,are ineffective for approximately one-third of depressed patients.Esketamine is a kind of rapid-act-ing antidepressant mainly targeting the central glutamatergic system,which is only approved by Food and Drug Administration for treating treatment-resistant depression and major depressive patients with severe suicidal tendency,owing to its potential addictive and psychotomimetic side effects.The search for anti-depressants that can rapidly produce effects with minimal side effects remains a key direction for disease treatment,and this endeavor necessitates a deeper understanding of the complex pathogenesis underlying the disease.Recent studies have revealed oxidative stress as a crucial factor in the pathogenesis of de-pression,and natural antioxidant methods such as exercise and composite dietary can effectively alleviate depressive symptoms,which could serve as promising therapeutic antidepressant approaches.Therefore,we review the close relationship between central glutamatergic system and depression onset,the influence of oxidative stress on glutamate neurotransmission,and the underlying molecular mechanisms involved,to provide novel ideas and drug targets for the prevention and treatment of the disease.
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