Prenatal Androgenization Induces Anxiety-Like Behavior in Female Rats, Associated with Reduction of Inhibitory Interneurons and Increased BDNF in Hippocampus and Cortex.

Bojana Rankov Petrovic,Djuro Macut,Dragan Hrncic,Milica Velimirovic,Nela Puskas,Dusan Mladenovic,Valentina Cirkovic,Olivera Stanojlovic,Tatjana Simic,Sonja Suvakov,Ivan Zaletel,Aleksandra Rasic-Markovic,Djurdja Jovanovic

doi:10.1155/2019/3426092

Abstract

Anxiety is one of the most frequent psychiatric disorders. Despite the fact that most studies describe an anxiolytic effect of testosterone, hyperandrogenemia in mothers is assumed to be related to an increased risk of mood disorders in their offspring. An increasing body of scientific evidence suggests that an altered expression of interneuronal markers of the hippocampus may be the cause of anxiety. The aim of this study was to examine the influence of maternal hyperandrogenemia on behavioral parameters of anxiety-like behavior, neuropeptide Y (NPY) and parvalbumin (PV) expression in the hippocampus, and the level of the brain-derived neurotrophic factor (BDNF) in the hippocampus and cerebral cortex. Pregnant female Wistar albino rats were treated with testosterone undecanoate on the 20th day of gestation. Anxiety-like behavior in adult female offspring was evaluated by the elevated plus maze test and the open field. The number of PV and NPY immunoreactive cells in the hippocampus was determined immunohistochemically. The level of BDNF expression in the hippocampus and cerebral cortex was analyzed with the Western blot test. Prenatal hyperandrogenization increased anxiety-like behavior in female offspring and decreased expression of NPY+ and PV+ in the CA1 region of the hippocampus as compared to the control group. BDNF expression in the hippocampus and cerebral cortex of prenatally androgenized female offspring was significantly increased in comparison with the controls. Prenatal hyperandrogenization may be the cause of anxiety-like behavior in female offspring. Decrease in NPY and PV expression in the hippocampus may explain the possible mechanism of hyperandrogenization induced anxiety.

Highlights

Genetic sex predisposes the endogenous hormonal milieu which further on causes fine variances in the structure and functioning of the central nervous system [1]
The relation between brainderived neurotrophic factor (BDNF), the survival of inhibitory interneurons and anxiety is still not established. Based on this background the aim of the present study was to determine the effects of prenatal androgenization on anxiety-like behavior, neuropeptide Y (NPY) and PV immunoreactivity in the hippocampus, and BDNF levels in the hippocampus and the cerebral cortex in female offspring
Prenatal treatment with testosterone undecanoate significantly reduced time spent in the open arms as compared to the control group (U=25.5, Z=2.17, p < 0.05) (Figure 1), while the number of entries in the open arms was not affected by T treatment (U=37.5, Z=1.37, p> 0.05)

Summary

Introduction

Genetic sex predisposes the endogenous hormonal milieu which further on causes fine variances in the structure and functioning of the central nervous system [1]. A larger hippocampus in males is evident in early life and correlates with larger number of neurons and glial cells [5, 6] Much of these is ascribed to effects of testosterone through induction of spines and spine synapses on the dendrites of CA1 pyramidal neurons, BioMed Research International as well as alterations in long-term synaptic plasticity (LTP) and hippocampally dependent cognitive behaviors [7]. How these effects occur remains largely unknown

Objectives

Methods

Results

Conclusion