• the Korean Society for Brain and Neural Sciences


Original Article

Exp Neurobiol 2019; 28(2): 270-278

Published online April 30, 2019

© The Korean Society for Brain and Neural Sciences

Glutamine Supplementation Ameliorates Chronic Stress-induced Reductions in Glutamate and Glutamine Transporters in the Mouse Prefrontal Cortex

Ji Hyeong Baek, Arul Vignesh, Hyeonwi Son, Dong Hoon Lee, Gu Seob Roh, Sang Soo Kang, Gyeong Jae Cho, Wan Sung Choi, and Hyun Joon Kim*

Department of Anatomy and Convergence Medical Sciences, Institute of Health Sciences, Bio Anti-aging Medical Research Center, Gyeongsang National University School of Medicine, Jinju 52727, Korea.

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-55-772-8034, FAX: 82-55-772-8039
These authors contributed equally to this work.

Received: November 27, 2018; Revised: March 28, 2019; Accepted: April 7, 2019

Chronic immobilization stress (CIS) induces low levels of glutamate (Glu) and glutamine (Gln) and hypoactive glutamatergic signaling in the mouse prefrontal cortex (PFC), which is closely related to the Glu-Gln cycle. A Gln-supplemented diet ameliorates CIS-induced deleterious changes. Here, we investigated the effects of CIS and Gln supplementation on Glu-Gln cycle-related proteins to characterize the underlying mechanisms. Using the CIS-induced depression mouse model, we examined the expression of 11 proteins involved in the Glu-Gln cycle in the PFC. CIS decreased levels of glutamate transporter 1 (GLT1) and sodium-coupled neutral amino acid transporter (SNAT) 1, SANT2, SNAT3, and SNAT5. Gln supplementation did not affect the non-stressed group but significantly increased GLT1 and SNATs of the stressed group. By immunohistochemical analysis, we confirmed that SNAT1 and SNAT2 were decreased in neurons and GLT1, SNAT3, and SNAT5 were decreased in astrocytes in the medial PFC of the stressed group, but Gln-supplemented diet ameliorated these decrements. Collectively, these results suggest that CIS may cause depressive-like behaviors by decreasing Glu and Gln transportation in the PFC and that a Gln-supplemented diet could prevent the deleterious effects of CIS.

Graphical Abstract

Keywords: Depressive disorder, Stress, Glutamate, Glutamine, Prefrontal cortex