Exp Neurobiol.  2019 Apr;28(2):270-278. 10.5607/en.2019.28.2.270.

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

• Baek JH
• Vignesh A
• Son H
• Lee DH
• Roh GS
• Kang SS
• Cho GJ
• Choi WS
• Kim HJ

• KMID: 2450218
• DOI: http://doi.org/10.5607/en.2019.28.2.270

Abstract

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.

Keyword

Depressive disorder; Stress; Glutamate; Glutamine; Prefrontal cortex

MeSH Terms

Amino Acid Transport System X-AG
Amino Acid Transport Systems
Animals
Astrocytes
Depression
Depressive Disorder
Diet
Glutamic Acid*
Glutamine*
Immobilization
Mice*
Neurons
Prefrontal Cortex*
Transportation
Amino Acid Transport System X-AG
Amino Acid Transport Systems
Glutamic Acid
Glutamine