Involvement of Nitric Oxide, Neurotrophins and HPA Axis in Neurobehavioural Alterations Induced by Prenatal Stress

Abstract

Several studies suggest that negative emotions during pregnancy generate adverse effects on the cognitive, behavioural and emotional development of the descendants. The psychoneuroendocrine pathways involve the transplacentary passage of maternal glucocorticoids in order to influence directly on fetal growth and brain development.Nitric oxide is a gaseous neurotransmitter that plays an important role in the control of neural activity by diffusing into neurons and participates in learning and memory processes. It has been demonstrated that nitric oxide is involved in the regulation of corticosterone secretion. Thus, it has been found that the neuronal isoform of nitric oxide synthase (nNOS) is an endogenous inhibitor of glucocorticoid receptor (GR) in the hippocampus and that nNOS in the hippocampus may participate in the modulation of hypothalamic-pituitary-adrenal axis activity via GR.Neurotrophins are a family of secreted growth factors consisting of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and NT4. Although initially described in the nervous system, they regulate processes such as cell survival, proliferation and differentiation in several other compartments. It has been demonstrated that the NO-citrulline cycle acts together with BDNF in maintaining the progress of neural differentiation.In the present chapter, we explore the interrelation between nitric oxide, glucocorticoids and neurotrophins in brain areas that are key structures in learning and memory processes. The participation of this interrelation in the behavioural and cognitive alterations induced in the offspring by maternal stress is also addressed.

The brain development of infants with intrauterine growth restriction: role of glucocorticoids

“…When stress affects the expression of GR in the hippocampus, the negative feedback regulation of the HPA axis will be affected. Many experimental studies have also confirmed that the presence of long-term increased GC will reduce the expression of GR, weaken the inhibition of the HPA axis and make the HPA axis stress response persistently, resulting in alterations of the hippocampus structure and function [28]. The GC exerts its physiological and pathological functions by activating GR and GR effects GCs.…”

Socioeconomic Deprivation, Adverse Childhood Experiences and Medical Disorders in Adulthood: Mechanisms and Associations

“…NO regulates a plethora of interactions between neuroimmune and neuroendocrine systems in physiologically normal and pathological conditions and neuronal nitric oxide synthase (nNOS) acts as a major modulator of processes governing the development of learning [241]. NO is involved in the regulation of corticosterone secretion and nNOS inhibits the activity of GR in the hippocampus resulting in the modulation of HPA axis activity [241, 242]. NO, in tandem with prostaglandins, plays a major role in enabling and regulating the activation of the HPA axis by CRH [243] (reviewed in [244]) and high NO levels exert broadly inhibitory effects [245].…”

So-Ochim-Tang-Gamibang, a Traditional Herbal Formula, Ameliorates Depression by Regulating Hyperactive Glucocorticoid Signaling In Vitro and In Vivo

“…It is hypothesized that the application of different stressors and the specific durations of the stress may cause alterations in the GR expression in certain rodent strains [ 7 ]. Furthermore, previous studies have revealed that the levels of neuronal nitric oxide synthase (nNOS), an endogenous inhibitor of GR in the hippocampus, increase upon exposure to stress [ 8 ] and are involved in the regulation of the HPA axis activity via GRs [ 9 ]. Thus, the inhibition of nNOS in the hippocampus leads to the decrease of the CORT concentration in the plasma and reduced CRH expression in the hypothalamus.…”