Fig. 2: Tyrosine (Y) shows antidepressive effects in chronic immobilization stress (CIS)-induced depressive mice via activation of glutamine synthetase (GS) in the medial prefrontal cortex (mPFC).

a and b Denitrative effect of Y on human recombinant GS and mouse mPFC lysate. c Scheme for Y diet supplementation, CIS, and behavioral tests. Changes in body weight and food intake during the experiment among groups (normal diet control group: CTL-N, Y diet control group: CTL-Y, normal diet stress group: STR-N, Y diet stress group: STR-Y, n = 7 per group). d–g Behavioral test results: open field test (d and e), tail suspension test (f), and sucrose preference test (g). h Plasma corticosterone level. i and j Reactive oxygen species (ROS)/reactive nitrogen species (RNS) levels in plasma and the mPFC, respectively. k and l Activity and expression levels of GS. m Nitrotyrosine-GS (N-Y-GS) level in the mPFC. n Representative Western blot images for GS, N-Y-GS, and α-tubulin. o–r Glutamate (Glu), glutamine (Gln), Tyr, and γ-aminobutyric acid (GABA) levels in the mPFC. s Amino acid (Glu, Gln, Tyr, and GABA) levels in plasma. t Traces of spontaneous excitatory postsynaptic currents (sEPSCs) in glutamatergic neurons of the mPFC. The changes of frequency (u), amplitude (v), and cumulative amplitude (w) among groups. Data are presented as the mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 (multiple comparisons test), and #P < 0.05 (individual comparison test) vs. CTL-N or STR-N groups.