Elsevier

Frontiers in Neuroendocrinology

Volume 41, April 2016, Pages 114-128
Frontiers in Neuroendocrinology

The maternal brain under stress: Consequences for adaptive peripartum plasticity and its potential functional implications

https://doi.org/10.1016/j.yfrne.2016.01.004Get rights and content

Highlights

  • There is a large degree of plasticity in the maternal brain during pregnancy and lactation.

  • Stress can significantly affect plasticity in the maternal brain.

  • Steroid and peptide hormones may mediate changes in maternal brain plasticity under basal and stressed conditions.

  • We discuss the implications of these changes in plasticity.

Abstract

The peripartum period represents a time during which all mammalian species undergo substantial physiological and behavioural changes, which prepare the female for the demands of motherhood. In addition to behavioural and physiological alterations, numerous brain regions, such as the medial prefrontal cortex, olfactory bulb, medial amygdala and hippocampus are subject to substantial peripartum-associated neuronal, dendritic and synaptic plasticity. These changes, which are temporally- and spatially-distinct, are strongly influenced by gonadal and adrenal hormones, such as estrogen and cortisol/corticosterone, which undergo dramatic fluctuations across this period. In this review, we describe our current knowledge regarding these plasticity changes and describe how stress affects such normal adaptations. Finally, we discuss the mechanisms potentially underlying these neuronal, dendritic and synaptic changes and their functional relevance for the mother and her offspring.

Introduction

There is a growing body of literature describing the physiological and behavioural adaptations, which occur across all mammalian species, during the transition from virginity to motherhood. These changes take place at numerous levels, and include neuroendocrine, behavioural, molecular and physiological adaptations, which act in concert to promote reproductive functions and ensure the survival. Thus, the onset of the complex array of maternal behaviours, such as maternal aggression, lactation, and nursing are a direct consequence of these changes. Additionally, towards the end of pregnancy, and into lactation, the response of the hypothalamic–pituitary–adrenal (HPA) axis to a variety of stressors is severely attenuated with a concomitant increase in basal cortisol/corticosterone (Brunton and Russell, 2008, Slattery and Neumann, 2008). Such dampened (re)activity of the HPA axis appears to be essential for the healthy development of the offspring, as high levels of circulating corticosteroids can cross the placenta and have severe consequences on foetal development (Wadhwa et al., 1993). Moreover, there are changes in anxiety-related behaviour, with increased anxiety reported in mid-to-late pregnancy, whereas anxiety is reduced in lactation (Brunton and Russell, 2008, Slattery and Neumann, 2008). There is a growing consensus that these maternal adaptations are not only important for the survival and development of the offspring, but also to protect the mother from the profound hormonal changes that are associated with birth (see below).

In addition to these well-characterised changes, one of the most striking changes that occurs during the peripartum period is a reduction in maternal brain volume; a finding shown in both humans (Oatridge et al., 2002) and rodents (Hillerer et al., 2014). In more detail, Oatridge et al. assessed total brain volume before pregnancy, during pregnancy and up to 13 months postpartum via MR imaging. They revealed that brain size was maximally reduced (on average 4.3% or 50.45 cm3, respectively) during pregnancy, accompanied by an increase in lateral ventricle size, and increased again after birth (Oatridge et al., 2002). Similarly, we were recently able to show that absolute (and relative) brain weights, as well as hippocampal volume were reduced on postpartum day (PD) 14 in rats compared with nulliparous rats (Hillerer et al., 2014).

These observed volumetric changes have been linked to peripartum-associated adaptations in structural and morphological features of maternal neurons since the maternal brain undergoes substantial macroscopic, microscopic, cellular and molecular changes in brain regions that are typically summarised as the “maternal circuitry” (Numan, 2007). This includes the maternal motivational system, which is comprised of brain regions such as the bed nucleus of the stria terminalis (BNST) and the medial preoptic area (MPOA), the non-specific motivational system including the nucleus accumbens (NAc), the ventral tegmental area (VTA), the olfactory bulb (OB), the medial amygdaloid nucleus (MeA), the anterior hypothalamic nucleus (AHN), the periaqueductal grey (PAG) and the paraventricular and supraoptic nuclei of the hypothalamus (PVN and SON, respectively). This “maternal circuitry”, which is conserved across mammals (for review see Swain, 2011), interconnects with the limbic system and the medial prefrontal cortex (mPFC). All of these regions are crucially involved in different aspects of maternal behaviour. It is speculated that these alterations in neuronal plasticity, dendritic morphology and spine characteristics, are necessary for the new mother to deal with the increasing demands of her novel environment. As outlined above, numerous regions within the hypothalamus undergo substantial peripartum plasticity, including glial retraction, altered dendritic length and branching, as well as altered number of axo-somatic and axo-dendritic synapses on oxytocin neurons, these findings have been expertly summarised in numerous reviews. Therefore, we would direct the interested reader to the following reviews (Hillerer et al., 2014, Langle et al., 2002, Oliet and Bonfardin, 2010, Theodosis et al., 2006) and within this review discuss other regions in more detail.

In this review we initially describe our current understanding of peripartum-associated changes in adult neurogenesis, synaptic plasticity and dendritic morphology; focusing particularly within the OB, amygdala, hippocampus and NAc. Thereafter, given the significant impact of stress on different aspects of neural plasticity in both males and females (for reviews see Galea et al., 2014, McEwen, 2013, Pawluski et al., 2015), we focus on the effects of repeated/chronic stress and corticosterone (CORT) exposure on these different forms of neural plasticity during the peripartum period. In the final sections, potential mechanisms underlying such basal- and stress-induced plasticity changes, as well as their functional implications are discussed.

Section snippets

Neurogenesis across the peripartum period

In the mammalian brain, there are two main areas that exhibit a high degree of adult neurogenesis throughout life, namely the granule cell layer (GCL) of the dentate gyrus (DG) and the subventricular zone (SVZ) of the lateral ventricles. Generally, neurogenesis consists of four main stages, namely cell proliferation, migration, differentiation and survival of cells, which can be visualised by the use of specific endogenous or exogenous proteins/markers. Factors that affect cell proliferation

Dendritic and synaptic remodelling across the peripartum period

The transition to motherhood and maternal experience does not only cause significant alterations in cell proliferation and cell survival as discussed above, but moreover leads to complex neuronal structural modifications. These changes include alterations in dendritic architecture, as well as the number and density of spines in different brain regions within the maternal network including the hippocampus, the OB, mPFC, the NAc and the MeA. Again with respect to hypothalamic plasticity, we would

Effect of peripartum stress on the plasticity of the maternal brain

The neural, dendritic and synaptic remodelling described above across the peripartum period are naturally-occurring, and presumably, necessary changes to ensure an adequate transition to motherhood. This may be especially true for rodent species, since the findings come mainly from mice and rats, which do not display high levels of spontaneous maternal behaviour. However, such structural plasticity and remodelling is also associated with stress exposure and stress-related disorders such as

Possible regulatory mechanisms involved in peripartum and stress-induced plasticity changes of the maternal brain

As stated above, the peripartum period is associated with dramatic fluctuations in gonadal (i.e. E2, PROG) and adrenal (i.e. CORT, CBG) steroid hormones (for review see Brunton and Russell, 2008, Galea et al., 2014, Neumann, 2003). While E2 and PROG levels show a sustained rise during pregnancy, with E2/PROG-levels reaching a 100/10-fold increase compared to the non-pregnant state by the end of pregnancy (Hendrick et al., 1998), there is a rapid drop of these hormones upon parturition with the

Functional implications of the peripartum neural plasticity

While the exact functional contributions of the aforementioned plasticity within the maternal brain are largely unknown, the extent of the changes indicate that they play an essential role, and might be fundamental for her physiological and mental health, as well as the survival of her offspring. In this following section, we summarise how the neuronal and morphological plasticity discovered to date may contribute to peripartum-associated changes in behaviour and the impact that stress may have

Summary

In summary, the reviewed literature supports the viewpoint that changes in neuronal plasticity and morphology in the PFC, NAc, MeA and hippocampus should be considered as belonging to the essential peripartum-associated adaptations that ensure the transition to motherhood. Given the importance of these systems in maternal behaviour and mood regulation, it can be speculated that the stress-induced alterations in adult neurogenesis, dendritic morphology and spine characteristics discovered to

Acknowledgments

The authors would like to thank the Deutsche Forschungsgemeinschaft (DFG SL141/4-1; DAS), the promotional program “Prosperamus!” P-12/01/001-FIS (KMH), the RISE-Project R-14/04/062-HIL (KMH) and the Stand-Alone-Project E-14/20/103-HIL (KMH) of the Paracelsus Medical Private University Salzburg Project for funding.

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