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

Abstract

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.

Milking It for All It’s Worth: The Effects of Environmental Enrichment on Maternal Nurturance, Lactation Quality, and Offspring Social Behavior

“…Milk samples ( n = 8) were placed onto a Mini Tube Rotator (Fisher Scientific catalog #88861051) overnight at 4°C to homogenize before analysis. Following the standard manufacturer’s instructions, commercially available ELISA kits were used to measure lactose content (Sigma-Aldrich catalog #MAK017; diluted 1:500; as outlined by Y. Chen et al, 2017 ; DeRosa et al, 2022 ), triglycerides (Abcam, catalog #ab65336; 1:1000 dilution), protein (Pierce BCA Protein Assay kit; catalog #23227; 1:50 dilution), and IgA (Bethyl Laboratories, catalog #E111-102; diluted to 1:1000) levels in milk. To measure corticosterone, the small sample assay protocol (#ADI-900-097, Enzo Life Sciences) was followed, as recommended by the manufacturer, using a 1:40 dilution ( DeRosa et al, 2022 ).…”

“…The fat layer of breastmilk is known to contain epithelial RNA ( Lemay et al, 2013 ; Alsaweed et al, 2015 ). To investigate maternal milk at the genome-wide level, total RNA ( n = 4–5 per housing group) was isolated from the milk fat layer from a subset of P10 milk samples using a previously published procedure ( Y. Chen et al, 2017 ; DeRosa et al, 2022 ). Milk was centrifuged for 5 min at 1000 × g (4°C) and the fat layer isolated.…”

Milking it for all it’s worth: The effects of environmental enrichment on maternal nurturance, lactation quality, and offspring social behavior

“…Following the standard manufacturer’s instructions, commercially available ELISA kits were used to measure lactose content (Sigma-Aldrich Cat. #MAK017; diluted 1:500; as outlined by Chen et al, 2017; DeRosa et al, 2022), triglycerides (Abcam, Cat. #ab65336; 1:1000 dilution), protein (Pierce™ BCA Protein Assay Kit; Cat.…”

“…# E111-102; diluted to 1:1000) levels in milk. To measure corticosterone, the small sample assay protocol (#ADI-900–097, Enzo Life Sciences, Farmingdale, NY) was followed, as recommended by the manufacturer, using a 1:40 dilution (DeRosa et al, 2022). We opted to only evaluate P10 milk samples on these measures because litters were appropriately standardized in size for this time point.…”

“…Total RNA (n=4-5 per housing group) was isolated from a subset of P10 milk samples using a previously published procedure (Chen et al, 2017; DeRosa et al, 2022). Milk was centrifuged for 5 minutes at 1,000 g (4°C) and the fat layer isolated.…”