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

Abstract

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.

Effects of Embryonic Inflammation and Adolescent Psychosocial Environment on Cognition and Hippocampal Staufen in Middle-Aged Mice

“…This result was consistent with those of previous studies that indicated that age-related decline in cognitive impairment begins at 12–13 months of age in this strain mouse ( Wang H. et al, 2010 ; Wang et al, 2020 ). Several studies have suggested that embryonic inflammation and adolescent stress can accelerate brain age-associate cognitive impairment ( Li X. W. et al, 2016 ; Bhagya et al, 2017 ; Wang et al, 2020 ). In contrast, an adolescent EE can relieve the deficits in hippocampal synaptic plasticity, memory, and anxiety caused by chronic stress ( Bhagya et al, 2017 ).…”

“…Our results showed that spatial learning and memory were impaired in the middle-aged mice. This result was consistent with those of previous studies that indicated that age-related decline in cognitive impairment begins at 12-13 months of age in this strain mouse Wang et al, 2020). Several studies have suggested that embryonic inflammation and adolescent stress can accelerate brain age-associate cognitive impairment Bhagya et al, 2017;Wang et al, 2020).…”

“…Several studies have indicated that cognitive impairment is associated with impaired synaptic plasticity. For example, embryonic inflammation and adolescent stress are shown to inhibit dendritic growth, induce neuronal remodeling and impaired synaptic transmission and plasticity, and lead to cognitive impairment in the aged mice ( Lesuis et al, 2019 ; Tellez-Merlo et al, 2019 ; Wang et al, 2020 ). In contrast, an adolescent EE can partly reverse behavioral and synaptic abnormalities resulting from embryonic inflammation ( Andoh et al, 2019 ).…”

The Impact of Systemic Inflammation on Alzheimer’s Disease Pathology

“…Moreover, repeated systemic LPS injections even lead to a prolonged elevation of Ab levels and cognitive deficits (38)(39)(40). Strikingly, pregnant mice exposed to repeated systemic LPS causes AD-related features including behavioral and neuropathological changes in their offspring (41).…”

Analysis of the area and the number of pulmonary alveoli through the normal aging process in CD1 mouse

“…Although the mouse strain CD1 has been widely used to examine multiple aspects of the general aging process [15][16][17], its alveolar morphometric analysis has not been reported yet.…”