Figure 7 | Scientific Reports

Figure 7

From: Caffeine protects against stress-induced murine depression through activation of PPARγC1α-mediated restoration of the kynurenine pathway in the skeletal muscle

Figure 7

Proposed model for the protective role of caffeine against CMS-induced depression. CMS-exposed mice showed depressive-like behaviour with an increase in plasma levels of kynurenine (KYN). Caffeine supplementation protected against depressive behaviours in CMS-exposed mice, accompanied by restoration of plasma concentrations of BBB-permeable, pro-neurotoxic KYN, and BBB-impermeable KYNA. In addition, caffeine administration activated kynurenine aminotransferase (KAT) which consumed KYN by converting it to KYNA in the skeletal muscles of the mice. Indeed, caffeine stimulated myotubes to sustain PGC-1α, a transcription factor for KAT, by inhibiting their proteasomal degradation. These events converge on KAT-mediated consumption of KYN, eventually leading to a reduction in plasma and brain levels of KYN.

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