Behavioral abnormalities with disruption of brain structure in mice overexpressing VGF

Abstract

VGF nerve growth factor inducible (VGF) is a neuropeptide induced by nerve growth factor and brain-derived neurotrophic factor. This peptide is involved in synaptic plasticity, neurogenesis, and neurite growth in the brain. Patients with depression and bipolar disorder have lower-than-normal levels of VGF, whereas patients with schizophrenia and other cohorts of patients with depression have higher-than-normal levels. VGF knockout mice display behavioral abnormalities such as higher depressive behavior and memory dysfunction. However, it is unclear whether upregulation of VGF affects brain function. In the present study, we generated mice that overexpress VGF and investigated several behavioral phenotypes and the brain structure. These adult VGF-overexpressing mice showed (a) hyperactivity, working memory impairment, a higher depressive state, and lower sociality compared with wild-type mice; (b) lower brain weight without a change in body weight; (c) increased lateral ventricle volume compared with wild-type mice; and (d) striatal morphological defects. These results suggest that VGF may modulate a variety of behaviors and brain development. This transgenic mouse line may provide a useful model for research on mental illnesses.

Higher serum VGF protein levels discriminate bipolar depression from major depressive disorder

“…In addition to the behavioral phenotypes, Mizoguchi et al (2017) also found that VGF-overexpressing mice showed reduced whole-brain and striatal volume and brain weight, increased lateral ventricle volume and the density of neurons in the dorsal medial region compared with wildtype mice. This may be due to the overexpression of VGF influences brain formation through interacting with Akt and GSK3β, because…”

“…In addition to the behavioral phenotypes, Mizoguchi et al () also found that VGF‐overexpressing mice showed reduced whole‐brain and striatal volume and brain weight, increased lateral ventricle volume and the density of neurons in the dorsal medial region compared with wild‐type mice. This may be due to the overexpression of VGF influences brain formation through interacting with Akt and GSK3β, because GSK3β is critical for brain development and VGF promotes phosphorylation of these proteins (Kim et al, ; Mizoguchi et al, ; Thakker‐Varia et al, ). Jiang et al() also discovered an interesting phenomenon, that adeno‐associated virus (AAV)‐Cre‐mediated vgf ablation in floxed VGF mice, in dorsal hippocampus (dHc) or nucleus accumbens (NAc), led to pro‐depressant or antidepressant behaviors, respectively, while dHc‐ or NAc‐AAV‐VGF overexpression induced opposite outcomes.…”

“…Interestingly, researchers found that compared with wild‐type mice, the VGF‐overexpressing mice also showed working memory impairment and a higher depressive state (Mizoguchi et al, ), the same behaviors as the depression‐like mice induced by VGF reduction. Beyond that, the VGF‐overexpressing mice also exhibited hyperactivity (Mizoguchi et al, ), which is inconsistent with the clinical symptoms of depression. In addition to the behavioral phenotypes, Mizoguchi et al () also found that VGF‐overexpressing mice showed reduced whole‐brain and striatal volume and brain weight, increased lateral ventricle volume and the density of neurons in the dorsal medial region compared with wild‐type mice.…”

“…Luckily, there was a study researching upregulation of VGF affects behavior and brain function in mice. Interestingly, researchers found that compared with wild-type mice, the VGF-overexpressing mice also showed working memory impairment and a higher depressive state (Mizoguchi et al, 2017), the same behaviors as the depression-like mice induced by VGF reduction. Beyond that, the VGFoverexpressing mice also exhibited hyperactivity (Mizoguchi et al, 2017), which is inconsistent with the clinical symptoms of depression.…”

“…Beyond that, the VGF‐overexpressing mice also exhibited hyperactivity (Mizoguchi et al, ), which is inconsistent with the clinical symptoms of depression. In addition to the behavioral phenotypes, Mizoguchi et al () also found that VGF‐overexpressing mice showed reduced whole‐brain and striatal volume and brain weight, increased lateral ventricle volume and the density of neurons in the dorsal medial region compared with wild‐type mice. This may be due to the overexpression of VGF influences brain formation through interacting with Akt and GSK3β, because GSK3β is critical for brain development and VGF promotes phosphorylation of these proteins (Kim et al, ; Mizoguchi et al, ; Thakker‐Varia et al, ).…”