The Beneficial Impact of Antidepressant Drugs on Prenatal Stress-Evoked Malfunction of the Insulin-Like Growth Factor-1 (IGF-1) Protein Family in the Olfactory Bulbs of Adult Rats.

Ewa Trojan,Władysław Lasoń,Joanna Ślusarczyk,Adam Roman,Katarzyna Głombik,Agnieszka Basta-Kaim,Bogusława Budziszewska,Marta Kubera

doi:10.1007/s12640-015-9575-3

Abstract

Insulin-like growth factor-1 (IGF-1) promotes the growth, differentiation, and survival of both neurons and glial cells, and it is believed to exert antidepressant-like activity. Thus, disturbances in the IGF-1 system could be responsible for the course of depression. To date, there have been no papers showing the impact of chronic antidepressant treatment on the IGF-1 network in the olfactory bulb (OB) in an animal model of depression. Prenatal stress was used as model of depression. Twenty-four 3-month-old male offspring of control and stressed mothers were subjected to behavioral testing (forced swim test). The mRNA expression of IGF-1 and IGF-1 receptor (IGF-1R) and the protein level of IGF-1 and its phosphorylation, as well as the concentrations of IGF-binding proteins (IGFBP-2, -4, -3, and -6), were measured in OBs before and after chronic imipramine, fluoxetine, or tianeptine administration. Adult rats exposed prenatally to stressful stimuli displayed not only depression-like behavior but also decreased IGF-1 expression, dysregulation in the IGFBP network, and diminished mRNA expression, as well as IGF-1R phosphorylation, in the OB. The administration of antidepressants normalized most of the changes in the IGF-1 system of the OB evoked by prenatal stress. These results suggested a beneficial effect of chronic antidepressant drug treatment in the alleviation of IGF-1 family malfunction in OBs in an animal model of depression.

Highlights

Apart from changes in neurotransmitters and the dysregulation of the immune and endocrine systems, studies have postulated that impairments in synaptic plasticity and neurogenesis play important roles in the development of depression (Bredt et al 2015)
These results suggested a beneficial effect of chronic antidepressant drug treatment in the alleviation of Insulin-like growth factor-1 (IGF-1) family malfunction in olfactory bulb (OB) in an animal model of depression
To determine whether chronic imipramine, fluoxetine, or tianeptine administration affected the behavioral changes evoked by the prenatal stress, we assessed the Porsolt test again

Summary

Introduction

Apart from changes in neurotransmitters and the dysregulation of the immune and endocrine systems, studies have postulated that impairments in synaptic plasticity and neurogenesis play important roles in the development of depression (Bredt et al 2015). Data have shown that depression might result from alterations in the Neurotox Res (2016) 29:288–298 neurotrophic factors expression in the central nervous system (CNS) (Branchi et al 2004). IGF-1 has combined effects on neural cell signaling and neurotrophic responses (Hoshaw et al 2008). It plays a crucial role in brain development, mainly through control of cell growth, differentiation, maturation, and survival. Great importance is ascribed to IGFBP-4, the only ‘classic’ binding protein, which does not exert any actions independently of IGF-1 (Mazerbourg et al 2004; Ning et al 2008). Some data have suggested that an appropriate balance between IGFBP-2 and IGFBP-4 is crucial for maintaining proper IGF-1 concentrations and biological activities

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Conclusion