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.