Bridging the mood and stress hormone levels between mothers and their babies: The study design and first preliminary results

The neurobiological mechanisms involved in the influence of post-partum maternal mood fluctuations on child development are far from being understood. Here we present the design of an ongoing study aimed to test the hypothesis that the mental state of the mother has an impact on her neonate which is manifested by similarities in the neuroendocrine function of the mother and the child. The hypothesis is being tested under both stress and non-stress conditions in mothers and babies aged 3–4 days and 7–9 months. The focus will be given to correlations with maternal postpartum mood. To confirm the correctness of methodological approaches and the feasibility of the study several preliminary analyses were performed. Salivary alpha-amylase activity as a marker of sympathetic activation and cortisol as the effective hormone of the hypothalamic-pituitary-adrenocortical axis were measured. The obtained results showed the feasibility of saliva sampling in neonates using a sampling time of 120 s. The analysis of cortisol in hair revealed increased concentrations during the third trimester of pregnancy, which is consistent with the knowledge of high cortisol concentrations during pregnancy. A positive correlation was observed between salivary cortisol values before and after the stress test in mother-infant dyads at both the post-partum period and 7–9 months thereafter. Understanding the mechanisms involved in “the bridge” between the mother and her baby will help to develop necessary interventions directed to help mothers in the early postpartum period

Representative pictures of glucocorticoid and mineralocorticoid receptor immunohistochemistry on adult (approx. 3-month-old) and pup (10-day-old) rat hippocampus.

<p>Arrows represent different insensity of immunoreactivity at corresponding areas.</p

Summary of the gluco- and mineralocorticoid differences during development.

<p>Adaptation to stress conditions is fundamental component of survival but the mechanisms seem to be different at different developmental stages (e.g. in adults and in pups). Stressors activate adrenocorticotropin (ACTH) secretion from the pituitary in both adults and pups. However, at the level of the adrenal gland, stimulation of corticosterone secretion is more pronounced in adults compared both to those in pups and to that of aldosterone secretion, while the opposite (namely more pronounced activation of aldosterone secretion) is present in pups. The lower glucocorticoid synthesizing 11β-hydroxysteroid dehydrogenase (11β-HSD1) and gluco- (GR) and mineralocorticoid receptor (MR) mRNA levels in pups seem to be protective mechanisms, preventing the organs (especially the brain) of the pups from excessive glucocorticoid effects. On the other hand, enhanced glucocorticoid degrading 11β-HSD2 expression may enable increased mineralocorticoid effects during the perinatal period.</p

Changes in plasma hormone and glucose concentrations during stress of hypoglycaemia in male Wistar rats (n = 12–16) at 90 minutes after the insulin injection.

<p>A. Blood glucose (mmol/l) – the effect of treatment and age were statistically significant (p<0.01). B. Plasma ACTH (pg/ml) – the effect of treatment was statistically significant (p<0.01). C. Plasma corticosterone (ng/ml) – the effects of age (p<0.01), treatment (p<0.01) and age x treatment (p<0.01) interaction were statistically significant. D. Plasma renin activity (ng/ml/h) – the effect of age (p<0.05) was statistically significant. E. Plasma aldosterone (pg/ml) – the effects of age (p<0.01), treatment (p<0.01) and age × treatment (p<0.05) interaction were statistically significant. Abbreviations: C: control, unstressed; S: stressed; **p<0.01 vs. appropriate control group; ##p<0.01 vs. appropriate adult group.</p

Representative pictures of glucocorticoid receptor immunohistochemistry on adult (approx. 3-month-old) and pup (10-day-old) rat brains.

<p>Selected area of the hypothalamus (PVN: nucleus paraventricularis hypothalami, MBH: mediobasal hypothalamus) and prefrontal cortex (PFC) are presented. Arrows represent different distribution of the GR immunoreactivity in adult and pup PFC regions.</p

In vitro ACTH sensitivity of adult and pup adrenal gland: secretion of corticosterone (A) and aldosterone (B) (n = 4).

<p>After 2 h preincubation we collected 3×15 min fractions with 10⁻¹⁰ M ACTH in the second fraction. AUC: area under the curve; the total secreted amount during the whole observation period. **p<0.01 vs. Control; #p<0.05, ##p<0.01 vs. Adults.</p

Hypoglycaemic stress: sampling 60 min after treatment.

<p>Blood samples were collected 60 minutes after insulin injection. The blood glucose level decreased (treatment p<0.01) and the ACTH level increased in the treated groups (treatment p<0.01). The corticosterone level increased after insulin-induced hypoglycaemia, but this elevation was significantly lower compared to adults (age p<0.01; treatment p<0.01 age × treatment p<0.01; treated adults vs. treated juveniles p<0.01). The aldosterone level was elevated after insulin injection in both age groups (treatment p<0.01). *p<0.05, **p<0.01 vs. Control; ##p<0.01 vs. Adult.</p

Changes in plasma hormone concentrations during stress of immune challenge at 120 minutes after lipopolysaccharid (LPS) treatment in male Wistar rats (n = 8–10).

<p>A. Plasma ACTH (pg/ml) – the effect of treatment was statistically significant (p<0.01). B. Plasma corticosterone (ng/ml) – the effects of age, treatment and age x treatment interaction were statistically significant (p<0.01). C. Plasma renin activity (ng/ml/h) – the effects of age, treatment and age × treatment interaction were significant (p<0.01). D. Plasma aldosterone (pg/ml) – the effects of age, treatment and age × treatment interaction were significant (p<0.01). Abbreviations: C: control, unstressed; S: stressed; **p<0.01 vs. appropriate control group; ##p<0.01 vs. appropriate adult group.</p

Glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11-beta-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD1 and 11β-HSD2) mRNA levels in the hypothalamus, hippocampus, prefrontal cortex, liver and kidney under non-stress conditions (n = 4).

<p>A. GR mRNA – the effect of age was statistically significant on all studied area (p<0.01). B. MR mRNA – the effect of age was significant on all studied area (p<0.01). C. 11β-HSD1 mRNA – the effect of age was statistically significant in the hippocampus, prefrontal cortex and kidney (p<0.01). D. 11β-HSD2 mRNA – the effect of age was significant in the hypothalamus, hippocampus and kidney (p<0.01). Abbreviations: Ht: Hypothalamus; Hc: Hippocampus; Pc: Prefrontal cortex; Lr: Liver; Kd: Kidney; ##p<0.01 vs. appropriate adult group.</p