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.
Highlights
VGF nerve growth factor inducible (VGF) is a neuropeptide induced by nerve growth factor and brainderived neurotrophic factor
This neuropeptide was first identified as a nerve growth factor (NGF)-induced protein in PC12 cells[12]
Later studies demonstrated that VGF is upregulated by other neurotrophic factors, including brain-derived neurotrophic factor (BDNF), epidermal growth factor (EGF), and neurotrophin-3 (NT-3) in PC12 cells and in primary cultures of cortical and hippocampal neurons[13, 14]
Summary
VGF nerve growth factor inducible (VGF) is a neuropeptide induced by nerve growth factor and brainderived neurotrophic factor. 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. Patients with depression and bipolar disorder express lower levels of VGF, while patients with schizophrenia and other cohorts of patients with depression express higher levels of VGF20–22 Based on these clinical findings, the phenotype of VGF germline knockout mice was investigated.
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