(713) The neuroprotective effect of maternal N-acetylcysteine supplementation during lactation period, on maternal-obese offsprings' cognitive function

Prenatal and lactation exposure to maternal obesity is associated with neurodevelopmental disorders in offspring later in life. During the intrauterine and post-natal developmental window, the fetal brain is particularly vulnerable to inflammation and oxidative stress. We hypothesize that supplementation of antioxidant agent N-acetyl cysteine (NAC), during lactation, a critical brain development period, to an obese mother will reduce oxidative stress of the fatus and prevent the development of cognitive impairment later in life.

Study Design:

15 young female CD1 mice were randomly assigned to different pharmacological groups: control (regular diet), HFD (high-fat diet prior mating, during pregnancy and lactation), HFD+NAC on lactation, CD (high-fat diet prior mating, during pregnancy and regular diet on lactation), and CD+NAC on lactation. NAC dose of 300 mg/Kg/day was given to mothers during lactation period via drinking water until weaning. Serum CRP levels were evaluated at weaning, whereas cognitive function was assessed in adulthood using Morris water maze (MWM) and object recognition tasks.   

Results:

HFD offspring had significantly higher CRP levels compared to control (7445+608 vs. 5473+ 434 ng/ml). NAC administration attenuated offspring CRP levels (5782+ 179) similar to control levels, while changing the diet alone during lactation, had no effect. Behaviorally, HFD offspring performed worse in learning phase of MWM task. Supplementation of NAC or/and diet switch during lactation improved learning ability of  HFD offspring. Probe day evaluation of memory capability showed a diet-dependent performance in MWM.

Conclusion:

Maternal obesity prior pregnancy and during lactation significantly impact offspring's spatial learning ability in adulthood and increase their basic CRP levels. Supplementation of anti-oxidant NAC to mothers during lactation may have a neuroprotective effect on dams learning ability and decrease offspring's basic inflammatory state.