Maternal gastrointestinal nematode infection enhances spatial memory of uninfected juvenile mouse pups

Abstract

The developing brain is particularly vulnerable to factors including maternal infection during pregnancy. Establishment of neural networks critical for memory and cognition begins during the perinatal period, when Heligmosomoides bakeri, a gastrointestinal (GI) nematode restricted to the maternal mouse intestine, has been shown to upregulate expression of long-term potentiation genes in the young rodent pup brain. We explored the impact of maternal infection during pregnancy and early lactation on the spatial behavior of uninfected male and female juvenile mice. Pre-weaned pups of H. bakeri infected dams exhibited less exploratory behaviour compared to pups of uninfected dams on postnatal day (PD) 16 but not PD 17, possibly reflecting a transient fear of an unfamiliar environment and/or a brief neurodevelopmental delay. Our two spatial memory tests show for the first time an enhancement of spatial memory in response to maternal nematode infection regardless of pup sex. At PD 17, pups of infected dams expressed object location memories after 3 h in the Object Location Test whereas offspring of uninfected mothers did not. In addition, at PD 34, juveniles of infected mothers retained their ability to find the escape hole in the Barnes Maze Test for one week whereas offspring from uninfected mothers did not. This finding is even more striking given that spatial memory was positively associated with pup length, yet this maternal infection impaired linear growth of pups. Thus, the positive impact of maternal infection on spatial memory countered any impairment associated with the shorter length of the pups. Overall, these novel findings indicate that a maternal GI nematode infection during pregnancy and lactation positively influences the spatial memory of uninfected juvenile offspring with potential fitness implications for the next generation.

Maternal gastrointestinal nematode infection alters hippocampal neuroimmunity, promotes synaptic plasticity, and improves resistance to direct infection in offspring.

“…CaMKIIα and β and PKCα have distinct and crucial roles in neuronal plasticity and memory; loss of CaMKIIα, CaMKIIβ [56][57][58][59] or PKCα [55] result in severe LTP and spatial memory impairments. Taken together, higher expression of Gria1 and Grin2a, lower expression of Gria4, with higher expression of Camk2a, Camk2b and Prkca would be expected to promote LTP, as demonstrated here, and facilitate spatial memory in response to maternal infection, as we previously reported [10] .…”

“…Our lab has focused on the in uence of maternal GI nematode infection upon neurodevelopment and cognitive function in offspring, using the murine laboratory model Heligmosomoides bakeri (also known as Heligmosomoides polygyrus), a strictly intestinal nematode with a direct lifecycle [9] . Maternal H. bakeri infection allowed 17 day-old offspring to retain object location memories for 3 hours and three week-old offspring to retain long-term spatial reference memories for 7 days, in contrast to offspring of uninfected dams who could not retain these memories [10] . As rodents are not capable of retaining object location memories for 2 + hours until postnatal day (PD) 24, nor can they retain long-term spatial reference memories for 7 days until PD 60 [11,12] , these ndings suggested that the maturational processes needed to recall these spatial memories were accelerated in response to maternal H. bakeri infection [10] .…”

“…As rodents are not capable of retaining object location memories for 2 + hours until postnatal day (PD) 24, nor can they retain long-term spatial reference memories for 7 days until PD 60 [11,12] , these ndings suggested that the maturational processes needed to recall these spatial memories were accelerated in response to maternal H. bakeri infection [10] . We also reported that maternal H. bakeri infection increased the expression of genes associated with long-term potentiation (LTP) in the brain of uninfected neonates [13,14] , raising the possibility that this could underlie the enhanced spatial memory [10] .…”

“…LTP in the mouse hippocampal slice preparation is found in the second postnatal week [22] ; however depending on strain, this can be delayed until 4-to 5-weeks [23] . Neuroin ammation inhibits LTP, whereas several immunoregulatory factors can promote LTP [24] ; as H. bakeri induces an immunoregulatory response, we hypothesized that maternal H. bakeri infection will induce an immunoregulatory response in the offspring hippocampus, promoting hippocampal LTP to explain the earlier development of spatial memory in the offspring of infected dams [10] .…”

Helminth-host-environment interactions: Looking down from the tip of the iceberg

“…As early as the 1990s, there was interest in whether helminths influenced host cognition (Townsend et al 2022). Recently, maternal infection with H. bakeri was shown to improve spatial memory of uninfected mouse offspring (Noël et al 2022). After a repeated trickle infection during pregnancy and lactation, spatial learning and memory of the uninfected pups were tested beginning at 23 days of age using a Barnes Maze.…”