Maternal high-fat diet impairs cognitive performance by altering hippocampal GRP78/PERK axis and BDNF expression in adult female rat offspring: the potential protective role of N acetylcysteine

Abstract

Maternal high fat diet (HFD) affects the neurodevelopment of offspring and has long-term consequences on cognitive behavior. This study investigated changes occurring in GRP78 and PERK, important markers of endoplasmic reticulum stress (ERS) signaling, in the hippocampus of female adult rats exposed to maternal HFD, and in brain-derived neurotrophic factor (BDNF) signaling, with its important role in the regulation of cognitive behavior, and the potential neuroprotective effects of N-acetylcysteine (NAC) against these changes. A maternal obesity model was created with HFD (60% kcal). NAC (150 mg/kg) was administered intragastrically to both the NAC and HFD + NAC groups. The animals were mated at 12 weeks of age. The same diet was maintained throughout pregnancy and lactation. All female rat pups were subjected to the water maze test at eight weeks of age. Hippocampal GRP78 and PERK expressions increased in the HFD rats. However, maternal HFD suppressed hippocampal BDNF levels and reduced hippocampal neuronal volume. NAC supplementation reduced GRP78 and PERK expressions and increased BDNF and hippocampal volume values in the HFD + NAC group. At behavioral assessments, rats in the HFD group exhibited decreased memory and learning ability, but the HFD + NAC group exhibited stronger responses than the HFD group. Our findings suggest that the decrease in BDNF expression, which plays a role in memory and learning, after maternal HFD exposure may be due to ERS associated with increased GRP78 and PERK expressions. Furthermore, NAC supplementation may ameliorate the impairment in memory and spatial learning ability by attenuating hippocampal ERS in HFD rats.