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. Author manuscript; available in PMC: 2020 Apr 1.
Published in final edited form as: Mol Psychiatry. 2018 Jul 9;24(10):1523–1532. doi: 10.1038/s41380-018-0076-7

Figure 4. Diagrammatic representation of our major finding on leucine blockade of depression-like behavior in mice with or without inflammation.

Figure 4

A Overview of pathway of inflammation-induced depression and the anti-depressant effects of leucine. B Overview of kynurenine blood-to-brain transport across BMECs. Inflammation increases blood kynurenine resulting in more kynurenine binding to LAT1 and being transported into the brain, which is blocked by the LAT1 specific antagonist BCH. Leucine competitively inhibits kynurenine binding to LAT1 and thus reduces blood-to-brain transport of kynurenine. An efflux transporter predominates kynurenine brain-to-blood transport, which is not LAT1 and is not bound by leucine. This efflux transporter extrudes kynurenine produced locally by inflammation.