Maternal dietary zinc supplementation prevents aberrant behaviour in an object recognition task in mice offspring exposed to LPS in early pregnancy

Abstract

Maternal infection during pregnancy is associated with an increased risk of neurodevelopmental damage. While the mechanism is unclear accumulating evidence suggests that the maternal inflammatory response may be responsible. Metallothionein (MT) is a zinc (Zn)-binding protein that when induced in the mother’s liver during the acute phase response has been found to cause a fetal Zn deficiency. Infection-mediated fetal Zn deficiency in early pregnancy has been shown to cause teratogenicity which can be prevented by dietary Zn supplementation throughout pregnancy. This study examined whether cognitive impairments can be caused by lipopolysaccharide (LPS) administration early in pregnancy and whether dietary Zn supplementation can ameliorate these changes. Maternal inflammation induced by LPS at gestation day (GD) 8 did not affect spatial learning or memory of adult mice offspring in a water cross-maze escape task. However, in an object recognition task, where control mice demonstrated good visual recognition memory by exploring a novel object more than a familiar object, LPS-treated offspring demonstrated abnormal perseverant exploration towards the familiar object that cannot be explained in full by impaired object recognition memory. In comparison, offspring of mice from dams given LPS and dietary Zn supplementation displayed normal object recognition task performance. Microarray analysis on the brain of GD 12 fetuses did not identify any differentially expressed genes between treatment groups. This study demonstrates that LPS administration in early pregnancy can cause an anomaly in object recognition that can be measured in adult offspring. This aberrant behaviour can be prevented by dietary Zn supplementation during pregnancy, thus providing a nutritional strategy to limit neurodevelopmental damage caused by infections early in pregnancy.