Gsk3β aggravates the depression symptoms in chronic stress mouse model

Abstract

Depression caused by genetic and environmental factors is acomplicated disease. Here, it is demonstrated that glycogen synthase kinase-3β is highly expressed and phosphorylated in the brain of a chronic stress mouse. Inhibition of glycogen synthase kinase-3β leads to decreased depression-like symptoms which manifest in open-field test, tail-suspension test, forcedswim test, and a novelty suppressed feeding test. It was also found that β -catenin is attenuated, and its target genes Cyclin D1 and c-Myc are down-regulated. Glycogen synthase kinase-3β was also found to inhibit Erk-Creb-BDNF signaling. These results show that glycogen synthase kinase-3β may promote the progression of depression. Therefore, targeting glycogen synthase kinase-3β may be an effective therapeutic strategy.The chronic stress mouse model was produced via severe metamorphic stress [14,15]. The detailed procedure is illustrated in Fig. 2, stimulations were as follows: 1. fasted for 12 h; 2. no water for 12 h; 3. swimming in cold water (10 • C) for 6 min; 4. tail clamp (clamp at 1 cm away from the caudal root) for 1 min; 5. housed in

Network Pharmacology and Molecular Docking Analyses of Mechanisms Underlying Effects of the Cyperi Rhizoma-Chuanxiong Rhizoma Herb Pair on Depression

“…The target-pathway network illustrated that AKT1, MAPK1, GSK3B, TNF, MTOR, and PTEN were core targets enriched in key signaling pathways that played crucial roles in the treatment of depression by CCHP. GSK3B may be involved in the development of depression by inhibiting Erk-CREB-BDNF signaling [ 99 ], and PI3K/Akt/mTOR/GSK3B signaling may be the mechanism underlying the rapid antidepressant effects [ 100 ]. TNF polymorphisms are associated with depression [ 65 ], and the suppression of TNF- α /TNFR1/NF- κ B signaling alleviated neuroinflammation and depression [ 101 ].…”

Hippocampal PPARα Plays a Role in the Pharmacological Mechanism of Vortioxetine, a Multimodal-Acting Antidepressant

“…In addition to PPARα, there are a lot of other proteins that not only control BDNF biosynthesis and neuroplasticity but also are implicated in depression, such as salt-inducible kinase 2, glycogen synthase kinase 3β and mammalian target of rapamycin ( Zhou et al, 2014 ; Peng et al, 2018 ; Jiang et al, 2019 ). These proteins may also play a role in the antidepressant actions of vortioxetine, and more extensive research will be exhibited in the future.…”

Gene expression in peripheral blood in treatment-free major depression

“…It is a multifunctional serine/threonine protein kinase that contributes to diverse cell functions, including gene expression, neurogenesis, neuroplasticity, cell survival, differentiation, migration, stress responses, and apoptosis, in the immune system, neurotransmitter systems, metabolism, and other functions (Hur and Zhou, 2010;Valvezan and Klein, 2012). GSK-3B has been found to mediate depressive symptoms in a chronic stress mouse model (Peng et al, 2018), and its inhibition has been shown to produce antidepressant-like effects in other animal models of depression (Gould et al, 2004;Kaidanovich-Beilin et al, 2004). Variation in grey matter volume in the hippocampus and superior temporal gyrus of depressed subjects has been associated with GSK3B polymorphisms (Inkster et al, 2009), and, in a post-mortem study of 20 depressed and 20 non-depressed subjects, Karege and collaborators found significant differences in protein levels of GSK-3B and β-catenin (Karege et al, 2012).…”

“…The canonical Wnt signaling pathway has garnered data that make it a promising system to explore in mood disorder research as well (Duman and Voleti, 2012). In psychiatry, evidence has accumulated on the participation on the Wnt signaling pathway in several diseases and related phenotypes (Mulligan and Cheyette, 2017) such as schizophrenia, (Miyaoka, Seno and Ishino, 1999;Levchenko et al, 2015;Hoseth et al, 2018), bipolar disorder (BD) (Matigian et al, 2007;Zandi et al, 2008;Sani et al, 2012;Winham et al, 2014;Pandey et al, 2015;Cuellar-Barboza et al, 2016;Hoseth et al, 2018), anxiety disorders (Zhao et al, 2018;Vidal et al, 2019), and depression (Saus et al, 2010;Enatescu et al, 2016;Peng et al, 2018;Vidal et al, 2019). Several members of the Wnt signaling pathway have been specifically linked to mood disorders.…”