YY1 (Yin‐Yang 1), a transcription factor regulating systemic inflammation, is involved in cognitive impairment of depression

Abstract

Aim: Clinical and preclinical studies suggest that alterations in the peripheral and brain immune system are associated with the pathophysiology of depression, also leading to changes in local glucose metabolism in the brain. Here, the authors identified Yin-Yang 1 (YY1), a transcription factor closely associated with central and peripheral inflammation.Methods: Plasma levels of YY1, interleukin (IL) 6, and IL-1β in major depressive disorder (MDD) were collected before and after treatment with vortioxetine, and correlation with clinical and cognitive scores was studied. Chronic unpredictable mild stress was treated with vortioxetine. Micropositron emission tomography (microPET) was used to analyze glucose metabolism and mRNA, and the protein level of the YY1-nuclear factor κB (NF-κB)-IL-1β inflammatory pathway were measured in related brain regions.Results: Plasma levels of YY1 and IL-1β were significantly increased in MDD and decreased after treatment with vortioxetine. Meanwhile, the level of YY1 in plasma was negatively correlated with cognitive functions in patients with MDD and positively correlated with the level of IL-1β in plasma. Compared with the control group, in chronic unpredictable mild stress rats, (microPET) analysis showed that the decrease of glucose metabolism in the hippocampus, entorhinal cortex, amygdala, striatum, and medial prefrontal cortex was reversed after treatment. mRNA and protein level of related molecular in YY1-NF-κB-IL-1β inflammatory pathway decreased in the hippocampus and was reversed by vortioxetine. Conclusion:The current study suggests that the YY1-NF-κB-IL-1β inflammatory pathway may play an essential role in both mood changes and cognitive impairment in depression, and may be associated with changes in glucose metabolism in emotion regulation and cognition. These findings provide new evidence for the inflammatory mechanisms of depression.

Integrated Transcriptomic and Proteomic Study of the Mechanism of Action of the Novel Small-Molecule Positive Allosteric Modulator 1 in Targeting PAC1-R for the Treatment of D-Gal-Induced Aging Mice

“…It is accompanied by a decrease in SIRT6 levels and an increase in YY1 levels in aged mice [14]. Data from clinical studies indicate that plasma levels of YY1 are significantly elevated in patients with major depressive disorder [28]. Notably, in a previous study, using chromatin immunoprecipitation, we showed that YY1 may be recruited by nuclear-translocated PAC1-R [21].…”

“…It should be mentioned that the result of the Western blot analysis showed that the effect of 0.1 µmol/kg/day SPAM1 was more significant than that of 100 µmol/kg/day SPAM1. In fact, the positive allosteric modulation site of PAC1-R may be able to detect some type of stress metabolites, such as PACAP (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38), which is a natural metabolite of the stress hormone PACAP38. The working mechanism of SPAM1 involves the imitation (mimicry) of some type of stress metabolites, such as PACAP (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38), to trigger self-defensive responses in the nervous system, including anti-senescence, neuroprotection, and nerve regeneration.…”

YY1 Lactylation Aggravates Autoimmune Uveitis by Enhancing Microglial Functions via Inflammatory Genes

“…[ 61 , 76 , 77 ] Similarly, human YY1 has been reported to participate in cancer development, modulation of neuroinflammation, and Th17 cell differentiation. [ 61 , 78 , 79 ] To further explore the translatability between human and mouse YY1, we compared both YY1 protein sequences on the UniProt website. The result showed that they shared high degree of homology (>98%), suggesting that our findings in mouse YY1 were largely representative of human YY1.…”

USP8 mitigates cognitive dysfunction of mice with sepsis‐associated encephalopathy

“…YY1 is correlated with cognitive impairment seen in depression. 38 Moreover, astrocytic YY1 plays an essential role in normal brain development, locomotor activity, motor coordination, and cognition. 39 After downregulating YY1, the disorders of learning and memory of SAE mice with USP8 overexpression were exacerbated, and behavioural deficits were aggravated.…”

“…YY1 is correlated with cognitive impairment seen in depression 38 . Moreover, astrocytic YY1 plays an essential role in normal brain development, locomotor activity, motor coordination, and cognition 39 .…”