VEGF Treatment Ameliorates Depression-Like Behavior in Adult Offspring after Maternal Immune Activation

Abstract

Maternal immune activation (MIA) during pregnancy impacts offspring neurodevelopmental trajectories and induces lifelong consequences, including emotional and cognitive alterations. Using the polyinosinic:polycytidilic acid (PIC) MIA model we have previously demonstrated enhanced depression-like behavior in adult MIA offspring, which was associated with reduced expression of the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) in the hippocampus. Since VEGF mediates the effects of various antidepressant agents, we here set out to explore whether VEGF administration could rescue the depression-like behavioral deficits in MIA offspring. To test our hypothesis, control and MIA offspring were intracerebroventricularly (i.c.v.) infused with either VEGF or vehicle solution and depression-related behavior was assessed in the sucrose preference test (SPT) and the tail suspension test (TST). As a surrogate of VEGF activity, the phosphorylation of the extracellular signal-regulated kinase (ERK) in hippocampus was quantified. We found that VEGF treatment reduced depression-related behavioral despair in the TST in MIA offspring but had no effect on anhedonia-like behavior in the SPT. While VEGF administration induced the phosphorylation of ERK in the hippocampus of control offspring, this effect was blunted in the MIA offspring. We conclude that VEGF administration, at the dosage tested, beneficially affects some aspects of the depression-like phenotype in the adult MIA offspring, inviting further studies using different dosage regimes to further explore the therapeutic potential of VEGF treatment in MIA-related changes in brain function and behavior.

Cross Brain–Gut Analysis Highlighted Hub Genes and LncRNA Networks Differentially Modified During Leucine Consumption and Endurance Exercise in Mice with Depression-Like Behaviors

“…Sideromenos and colleagues indicated that VEGF could modulate depression-related behavior and be the candidate antidepressant agent [ 65 ]. In addition, they found that treatment based on VEGF stimulated the phosphorylation of ERK in the hippocampus.…”

Carnitine and Depression

“…Neurotrophic factors are associated with the pathogenesis of depression ( 87 , 88 ). The decreased concentrations of BDNF ( 89 ), glial cell line-derived neurotrophic factor (GDNF), Artemin (ARTN) ( 90 ), nerve growth factor (NGF) ( 91 ), and vascular endothelial growth factor (VEGF) ( 92 ) are a good repetitive finding in depression. Supplementation of LAC can induce neuroprotective and neurotrophic effects of the peripheral nervous system by increasing the level of brain-derived neurotrophic factor (BDNF), especially in the hippocampus and prefrontal cortex ( 93 – 95 ).…”

Vascular Endothelial Growth Factor May Be Involved in the Behavioral Changes of Progeny Rats after Exposure to Ceftriaxone Sodium during Pregnancy

“…Previous studies show that VEGF, a disulfide-bonded glycoprotein dimer promotes endothelial growth, is an important factor in angiogenesis, and has neurotrophic effects on glial and neuronal cells [ 35 ]. VEGF treatment also improves the depression-like behavior of adult offspring due to maternal immune activation [ 36 ]. These findings suggest that S24-7 contributed to the behavioral changes of offspring rats by regulating the level of VEGF.…”