Effects of Vitamin C deficiency on increased anxiety-like behavior induced by social-defeat stress in mice Taiga

Background and objectives: We have previously shown that Vitamin C (VC) deficiency for 1 week increases anxiety-like behavior in osteogenic disorder Shionogi rats, which are unable to biosynthesize VC. To investigate the effects of VC deficiency on stress-induced behavioral changes, we measured anxiety-like behavior under social-defeat stress using senescence marker protein–30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice, which are unable to biosynthesize VC. Methods: 3-week-old male SMP30/GNL KO mice were divided into two groups; one was provided with water containing sufficient amount of VC (VC+) and the other with water without VC (VC-) for 42 days. On days 25–34, half of the mice in each group were exposed to social-defeat stress by being repeatedly subjected to larger and aggressive ICR mice (S+), while the other half were not exposed to social-defeat stress (S-). On days 35–38 and 41, anxiety and depression levels were assessed by the elevated plus maze test (EPMT), open field test (OFT), and tail suspension test (TST), respectively. Dissection was performed on day 42; plasma and organs were collected, and the levels of plasma and brain VC, brain neurotransmitters, plasma corticosterone, and brain TBARS were measured. Results: Body weight did not differ significantly among the four groups throughout the experimental period. Total VC levels in plasma and cortex were significantly reduced by VC deficiency. In the EPMT, mice in the VC-/S+ group did not appear in the open arm for the first 5 minutes and demonstrated significantly reduced open arm activity compared with that of the mice in the VC+/S+ group; however, decreased open arm activity due to VC deficiency was not observed in the non-stressed mice. Center area activity in the OFT was decreased and plasma corticosterone level was increased owing to social-defeat stress but was not affected by VC deficiency. In the TST, there were no significant differences in immobility time among groups. Prefrontal cortex dopamine levels were significantly reduced and cerebellar TBARS levels were significantly increased by VC deficiency but were not affected by social-defeat stress. Conclusion: Vitamin C deficiency augments increased anxiety-like behavior with social-defeat stress in the EPM test.