Dihydromyricetin ameliorates social isolation-induced anxiety by modulating mitochondrial function, antioxidant enzymes, and BDNF

Stress has been implicated in the etiology of neurological and psychological illnesses. Chronic social isolation (SI) is a psychological stressor that provokes neurobehavioral changes associated with psychiatric disorders, including anxiety disorders. Mitochondria dysfunction and oxidative stress are hallmarks of anxiety pathogenesis. Here we demonstrate the effects of SI-induced stress on mitochondrial function, antioxidative enzymes, autophagy, and brain derivative neurotrophic factor (BDNF). SI induced a reduction in electron transport chain subunits C–I, C-II, and C-VI and an increase in hydrogen peroxide. Treatment with dihydromyricetin (DHM), extracted from Ampelopsis grossedentata, counteracted these changes. A dramatic increase in several primary mitochondrial antioxidative enzymes such as superoxide dismutase 2 (SOD2), heme oxygenase-1 (HO-1), peroxiredoxin-3 (PRDX3), and glutathione peroxidase 4 (GPX4) was observed after SI and a repeated episode of SI. Both SI and repeated SI induced a reduction in sequestosome 1 (SQSTM1/p62). However, only repeated SI modulated autophagy primary protein beclin-1 (Bcl-1). In addition, SI and repeated SI modulated the BDNF-TrkB signaling pathway and the phosphorylation of the downstream extracellular signal-regulated MAP kinase1/2 (p-Erk p42 and p-Erk p44) cascade. DHM treatment ameliorated these changes. Collectively, we demonstrated that DHM treatment counteracted the effects of SI and repeated SI on antioxidative enzymes, autophagy, and the BDNF-TrkB signaling pathway. These findings highlight the molecular mechanisms that partially explain the anxiolytic effects of DHM.

Abstract licence: CC BY-NC-ND

1. 28.

   Brain-Derived Neurotrophic Factor (BDNF) protein levels in anxiety disorders: systematic review and meta-regression analysis · 2013

2. 39.

   Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice · 2016

3. 40.

   Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness · 2016

4. 49.

   Loneliness in the general population: prevalence, determinants and relations to mental health · 2017

5. 68.

   Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic · 2021

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