Fig. 6

Overview of the neurobiological processes, associated with HFD-induced and UCMS-induced emotional alterations respectively. In line with the initial expectations, inflammation was selectively reported in the model of HFD-related depression, as shown by increased expression of markers of microglial activation in the HC and PFC. Consistent with this, HFD mice also displayed activation of the KYN and BH4 pathways, which are known to trigger inflammation-driven depression. This activation, which was particularly sustained in the HC, was associated with impaired local monoaminergic neurotransmission, notably the 5-HT system. It concomitantly promoted glutamate excitotoxicity and oxidative stress, favoring in turn neurotoxicity. Of note, these neurobiological changes that likely contribute to emotional alterations were also found in the UCMS depression model, but importantly, upstream triggering mechanisms were in that case independent from inflammation. The two experimental conditions enable, respectively, to dissociate inflammation-related vs. inflammation-unrelated depressive symptoms. Arrows indicate activation and dotted T-bars inhibition/impairment