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

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.

Anxiogenic Potential of Experimental Sleep Fragmentation Is Duration‐Dependent and Mediated via Oxidative Stress State

“…Loss of the hippocampal neurons coupled with anxiety-related behavior has been demonstrated in other studies [ 30 , 67 ]. However, it should still be underlined that hippocampal PV+ interneurons [ 68 ] are involved in the behavioral patterns, including fear and anxiety [ 69 ], although they do not influence the mechanism of sleep fragmentation-evoked anxiety-like behavior.…”

Early-life stress alters affective behaviors in adult mice through persistent activation of CRH-BDNF signaling in the oval bed nucleus of the stria terminalis

“…Importantly, the BNST is a critical node of the avoidance circuitry 90 , which has mutual projections to the central amygdala 53 , PVN 91 , ventral tegmental area (VTA) 92 and lateral hypothalamus 93 , whereas it further receives input from the ventral subiculum 94 that is involved in HPA-negative feedback. Although ELS effects on the hippocampus 7 , dorsal raphe 23 , and VTA 95 are well-described, little is known about how ELS affects the BNST. Here we provide data implicating that a hyperactivate CRH circuitry in the ovBNST can result in increased HPA axis activation.…”

Attenuation of Anxiety-Like Behavior by Helichrysum stoechas (L.) Moench Methanolic Extract through Up-Regulation of ERK Signaling Pathways in Noradrenergic Neurons

“…The decrease of BDNF expression in the brain, especially in the hippocampus and PFC is associated with anxiety [ 36 ]. Indeed, the effect of some anxiolytic drugs can include the increase of neurotrophins [ 37 ].…”