Effect of lipopolysaccharide-mediated infection during pregnancy on the expression of mineralocorticoid receptor and dendritic spines in hippocampus of rat offspring

Abstract

Objective To observe the effect of lipopolysaccharide (LPS)-mediated infection during pregnancy on the expression of mineralocorticoid receptor (MR) and density of dendritic spines in CA1 region of the dorsal hippocampus of rat offspring, so as to explore the mechanisms for learning and memory injury of rat offspring which were infected during prenatal period, then to provide scientific experimental evidence for the prevention of prenatal infection-induced delayed neuropsychiatric sequelae which contributed to learning and memory dysfunction. Methods Ten-week-old female Sprague-Dawley rats (n=30) were matched with male rats (11). Pregnant rats were randomly divided into a control group (n=10) and an experimental group (n=20). The pregnant rats in experimental group were treated with LPS (66 μg/kg, intraperitoneally), and the pregnant rats in control group were intraperitoneally injected with same volume of saline on gestational day 10.On postnatal day 48, Morris water maze was used to estimate the ability of learning and memory; the brain tissues of offspring were taken and paraffin sections were stained with hemato-xylin eosin (HE) for histological observation of CA1 region of the dorsal hippocampus; frozen sections were treated with indirect immunofluorescence to observe the expression of MR in CA1 region of the dorsal hippocampus; Golgi-Cox method was used to observe the density of dendritic spines of CA1 region. Results In Morris water maze test, from the third day the time of escape latency in experimental group [the 3rd day: (42.603±9.837) s; the 4th day: (30.222±9.789) s; the 5th day: (28.808±12.526) s] was significantly higher than that of the control group [the 3rd day: (28.078±14.088) s; the 4th day: (20.692±13.099) s; the 5th day: (14.632±11.624) s] (the 3rd day: t=-3.274, P<0.01; the 4th day: t=-2.257, P<0.05; the 5th day: t=-3.213, P<0.01); the swimming time in the target quadrant [(14.660±7.337) times] and the number of crossing platform [(0.933±0.704) times] in experimental group were significantly decreased compared with those of the control group [time: (23.820±6.321) s; numbers: (2.000±0.756) times](t=3.663, 4.000, all P<0.01). Hematoxylin eosin staining showed that the nerve cells of the hippocampus in the control group distributed in order, nucleuses were round or oval, nucleoli were obvious, and chromatins were homogeneous; but the cells in the experimental group distributed in disorder and pathological changes were detected, such as cellular swelling, necrosis and obvious nuclear pyknosis.By immunofluorescence staining, the average optical density (AOD) of MR in CA1 region decreased significantly in the experimental group (0.067±0.017) compared with that of the control group (0.083±0.009)(t=2.644, P<0.05). In Golgi-Cox method, the density of dendritic spines in experimental group [(7.705±0.791)/10 μm] was below that of the control group [(9.655±1.391)/10 μm](t=3.852, P<0.01). Conclusions LPS-mediated infection during pregnancy might lead to hippocampus-dependent learning and memory dysfunction which might be associated with the reduced expression of MR and the low density of dendritic spines in CA1 region of the dorsal hippocampus. Key words: Lipopolysaccharide; Hippocampus; Mineralocorticoid receptor; Dendritic spine