Got Milk? Maternal immune activation during the mid-lactational period affects nutritional milk quality and adolescent offspring sensory processing in male and female rats

The neonatal environment requires a high level of maternal demand in terms of both breastfeeding and other forms of maternal care. Previous studies have underscored the importance of these maternal factors on offspring development and behavior. However, their contribution as dynamic variables in animal models of early life stress are often overlooked. In the present study, we show that lipopolysaccharide (LPS)-induced maternal immune activation (MIA) on postnatal day (P)10 immediately elevated milk corticosterone concentrations, which recovered by P11. In contrast, both milk triglyceride and percent creamatocrit values demonstrated a prolonged decrease following inflammatory challenge. Sustained inflammatory-induced changes to the nutritional quality of milk were also evidenced by its composition of microbial communities associated with inefficient energy and lipid metabolism. Nutritional deficits in early development have been associated with metabolic dysfunction later in life. Indeed, MIA-associated changes in the nutritional profile of milk were reflected by increased adolescent offspring bodyweights. While MIA did not decrease maternal care quality, there was a significant compensatory increase in maternal licking and grooming the day that followed the inflammatory challenge. However, this did not protect against disrupted neonatal huddling or later-life alterations in sensorimotor gating and mechanical allodynia in MIA offspring. Animal models of early life stress can impact both parents and their offspring. One mechanism that can mediate the effects of such stressors is changes to maternal lactation quality which our data show can confer multifaceted and compounding effects on offspring physiology and behavior.

Cumulative Effects of Prenatal and Concurrent Maternal Distress on Psychiatric Disorders in Adolescent Offspring

Background: Mental disorders affect 20% of children and adolescents globally and are among the most chronic and costly problems affecting youth. Offspring exposure to maternal disorders (depression, anxiety, and/or stress) prenatally as well as in adolescence increases the risk of psychopathology in adolescence. Objective: Exposure to maternal distress in pregnancy, as well as in adolescence, has independently been linked to psychopathology in youth. However, our understanding of the cumulative effects of exposure to maternal distress over time remains incomplete. Methods: 1964 participants enrolled in the 2014 Ontario Child Health Study (OCHS) aged 12-17 years completed the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). Maternal prenatal distress was defined as mother-reported depression and/or anxiety during pregnancy requiring treatment. Maternal concurrent distress was self-reported when offspring were 12-17 years of age using the Kessler Psychological Distress Scale (K6). We examined associations between increasing levels of exposure to maternal distress (no exposure, prenatal exposure only, concurrent exposure only, both prenatal and concurrent exposure) and the risk of psychiatric disorder in 12-17-year-olds. Results: The odds of major depressive disorder (OR=1.29, 95% CI: 1.01- 1.67) and ADHD (OR=1.30, 95% CI: 1.02-1.65) increased with increasing exposure to maternal distress. Associations between increasing levels of maternal distress and several psychiatric disorders were amplified in males. Conclusions: The accumulation of exposure to maternal distress over time predicts offspring psychopathology in adolescence and emphasizes the significance of the early detection of maternal distress and ongoing monitoring and intervention to reduce the burden of mental disorders in offspring.

Alteration of the Early Development Environment by Maternal Diet and the Occurrence of Autistic-like Phenotypes in Rat Offspring

Epidemiological and preclinical studies suggest that maternal obesity increases the risk of autism spectrum disorder (ASD) in offspring. Here, we assessed the effects of exposure to modified maternal diets limited to pregnancy and lactation on brain development and behavior in rat offspring of both sexes. Among the studied diets, a maternal high-fat diet (HFD) disturbed the expression of ASD-related genes (Cacna1d, Nlgn3, and Shank1) and proteins (SHANK1 and TAOK2) in the prefrontal cortex of male offspring during adolescence. In addition, a maternal high-fat diet induced epigenetic changes by increasing cortical global DNA methylation and the expression of miR-423 and miR-494. As well as the molecular changes, behavioral studies have shown male-specific disturbances in social interaction and an increase in repetitive behavior during adolescence. Most of the observed changes disappeared in adulthood. In conclusion, we demonstrated the contribution of a maternal HFD to the predisposition to an ASD-like phenotype in male adolescent offspring, while a protective effect occurred in females.