Ketamine ameliorates depressive-like behaviors in mice through increasing glucose uptake regulated by the ERK/GLUT3 signaling pathway

Abstract

To investigate the effects of ketamine on glucose uptake and glucose transporter (GLUT) expression in depressive-like mice. After HA1800 cells were treated with ketamine, 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino]-2-Deoxyglucose (2-NBDG) was added to the cells to test the effects of ketamine on glucose uptake, production of lactate, and expression levels of GLUT, ERK1/2, AKT, and AMPK. Adult female C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS), 27 CUMS mice were randomly divided into the depression, ketamine (i.p.10 mg/kg), and FR180204 (ERK1/2 inhibitor, i.p.100 mg/kg) + ketamine group. Three mice randomly selected from each group were injected with 18F-FDG at 6 h after treatment. The brain tissue was collected at 6 h after treatment for p-ERK1/2 and GLUTs. Treatment with ketamine significantly increased glucose uptake, extracellular lactic-acid content, expression levels of GLUT3 and p-ERK in astrocytes and glucose uptake in the prefrontal cortex (P < 0.05), and the immobility time was significantly shortened in depressive-like mice (P < 0.01). An ERK1/2 inhibitor significantly inhibited ketamine-induced increases in the glucose uptake in depressive-like mice (P < 0.05), as well as prolonged the immobility time (P < 0.01). The expression levels of p-ERK1/2 and GLUT3 in depressive-like mice were significantly lower than those in normal control mice (P < 0.01). Ketamine treatment in depressive-like mice significantly increased the expression levels of p-ERK1/2 and GLUT3 in the prefrontal cortex (P < 0.01), whereas an ERK1/2 inhibitor significantly inhibited ketamine-induced increases (P < 0.01).Our present findings demonstrate that ketamine mitigated depressive-like behaviors in female mice by activating the ERK/GLUT3 signal pathway, which further increased glucose uptake in the prefrontal cortex.

Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects

“…We indeed observed that the hippocampal HO-1/CO system is involved in the depressive-like state of the animals, and CO-RM-3 administration can reverse the depressive-like symptoms. CO is known for its neuroprotective effects in the cortical amygdala and hippocampal neurons ( Hettiarachchi et al, 2014 ; Wang et al, 2017 ; Riego et al, 2018 ); the brain regions are involved in depression ( Sheline et al, 2002 ; Whalen et al, 2002 ; Liu et al, 2017b ; Seo et al, 2017 ; Du Preez et al, 2021 ; Garro-Martinez et al, 2021 ; Li et al, 2021 ; Ouyang et al, 2021 ; Qin et al, 2021 ; Sindermann et al, 2021 ).…”

Involvement of kynurenine pathway between inflammation and glutamate in the underlying etiopathology of CUMS-induced depression mouse model

“…Lately, the kynurenine pathway has been reported to play a key role. At present, the pharmacological treatment of major depression is often suboptimal and associated with substantial side effects [ 9 – 12 ]. Therefore, it is essential to identify the exact mechanisms of depression.…”

Perspective Chapter: Ketamine, Depression, and Gender Bias

“…Also, in the prefrontal cortex, this expression was modulated by the estrous cycle [61]. The administration of ketamine in female mice exposed to chronic unpredictable mild stress was reported to be mediated via the extracellular-signal-regulated kinase and glucose transporter 3 (ERK/GLUT3) signaling pathway [62].…”