Lithium and glutamine synthetase: Protective effects following stress

•Translation of the protein glutamine synthetase (GS) in the brain can be measured in mice that carry LacZ as a reporter gene fused to the GS-promotor by staining histological slices with beta-galactosidase.•After 7 days of treatment with Lithium, NaCl or no treatment, group differences revealed increased GS-promotor activity in males after NaCl treatment indicating a stress effect of the injection and a protective effect of lithium.•There was no effect of treatment on GS-reporter activity in female mice indicating sex-specific stress coping.•Seven days Lithium treatment seemed to increase cell proliferation in the CA1 region, measured as the number of cells, but only in male mice.•Lithium treatment might protect against stress-induced neurobiological changes. Even though lithium is widely used as treatment for mood disorders, the exact mechanisms of lithium in the brain remain unknown. A potential mechanism affects the downstream target of the Wnt/β-catenin signaling pathway, specifically glutamine synthetase (GS). Here, we investigate the effect of lithium on GS-promoter activity in the brain. Over seven days, B6C3H-Glultm(T2A-LacZ) mice that carry LacZ as a reporter gene fused to the GS-promotor received either daily intraperitoneal injections of lithium carbonate (25 mg/kg) or NaCl, or no treatment. Following histochemical staining of β-galactosidase relative GS-promotor activity was measured by analyzing the intensity of the staining. Furthermore cell counts were conducted. GS-promotor activity was significantly decreased in female compared to male mice. Treatment group differences were only found in male hippocampi, with increased activity after NaCl treatment compared to both the lithium treatment and no treatment. Lithium treatment increased the overall number of cells in the CA1 region in males. Daily injections of NaCl might have been sufficient to induce stress-related GS-promotor activity changes in male mice; however, lithium was able to reverse the effect. Taken together, the current study indicates that lithium acts to prevent stress, rather affecting general GS-promoter activity.