Lipopolysaccharide exposure during late embryogenesis triggers and drives Alzheimer-like behavioral and neuropathological changes in CD-1 mice.

INTRODUCTION: Infections could contribute to Alzheimer's disease (AD) neuropathology in human. However, experimental evidence for a causal relationship between infections during the prenatal phase and the onset of AD is lacking. METHODS: CD-1 mothers were intraperitoneally received lipopolysaccharide (LPS) with two doses (25 and 50 μg/kg) or normal saline every day during gestational days 15-17. A battery of behavioral tasks was used to assess the species-typical behavior, sensorimotor capacity, anxiety, locomotor activity, recognition memory, and spatial learning and memory in 1-, 6-, 12-, 18-, and 22-month-old offspring mice. An immunohistochemical technology was performed to detect neuropathological indicators consisting of amyloid-β (Aβ), phosphorylated tau (p-tau), and glial fibrillary acidic protein (GFAP) in the hippocampus. RESULTS: Compared to the same-aged controls, LPS-treated offspring had similar behavioral abilities and the levels of Aβ42, p-tau, and GFAP at 1 and 6 months old. From 12 months onward, LPS-treated offspring gradually showed decreased species-typical behavior, sensorimotor ability, locomotor activity, recognition memory, and spatial learning and memory, and increased anxieties and the levels of Aβ42, p-tau, and GFAP relative to the same-aged controls. Moreover, this damage effect (especially cognitive decline) persistently progressed onwards. The changes in these neuropathological indicators significantly correlated with impaired spatial learning and memory. CONCLUSIONS: Prenatal exposure to low doses of LPS caused AD-related features including behavioral and neuropathological changes from midlife to senectitude.