Prenatal Exposure To Lipopolysaccharide Result In Specific Neurodevelopmental Damage In Rats

Neruodegenerative disorders ranks among the third causes of morbidity and mortality in adult population in most countries in the worls follwing the cardiovascular disease and tumor. Neurodegenerative disorders mainly refer to Alzheimer's disease, Parkinson's disease and Huntiongton disease. Alzheimer's disease is the most common neurodegenerative disorders in the aged. In our country, there are six million people with the Alzheimer's disease, and the tendency is more and more serious. Up to now, its underlying pathogenetic mechanisms are still not well elucidated, we only can delay the development of the disease in clinical. Thus, it is an important task to find a new etiological factor.In the past research of our own team, we found that prenatal exposure to LPS or zymosan stimulate the induction of proinflammatory cytokines TNF-a and IL-6 in amniotic fluid, placenta, chorioamnion,result in increases in blood pressure and body weight in rats offspring. In addition, our laboratory also found that Nfia, Nfib, Gap43 which might be correlated with efforts of immuno-inflammatory stimulus on embryo's brain development increased compared with control group by Affymetrix's GeneChip Rat Genome 230 Arrays. Based on our research team, this essay intends to study that the effects of intraperitoneal injections of LPS to pregnant rats on offspring's blood pressure, weight, life time and behavioral performance.Methods1. Sixteen pregnant Sprague-Dawley (SD) rats were used. All pregnant rats were treated at gestation days 8,10 and 12. The rats were randomly assigned to one of two groups: 1) Saline injections (i.p.),control group; 2) LPS injections (0.79㎎/㎏, i.p.), LPS group.2. The serums were collected in tail nick at 1 h after the last injection, the serum level of TNF-αwas detected by ELISA method.3. The pups'body weight was measured once every two months since second month until 20th month. Their systolic blood pressure were measured at the same time with tail-cuff method.4. Recorded the number of dead pup.5. Following a full term delivery, all offsprings was given behavioral tests at the age of 3 months,10 months and 20 months. The test included hot plate test,open field task and Morris water maze.6. Histological samples were taken for analysis at ages3,10 and 20months,Changes in synapse and astroglia were also studied using immunohistochemistry.Results1. The dams'serum level of TNF-αin LPS group was higher than that in control group (P<0.01). It showed that there was immuno-inflammatory response after LPS injection in rats.2. There were no significant differences in the number of progeny per dam (P>0.05). Meanwhile, no significant differences were discovered about the ratio of male births to female births in each litter (P>0.05). The body weights of newborn pups did not differ much between the LPS and control groups (P>0.05).3. All offspring of LPS group showed increased systolic blood pressure (P<0.05). They reached the standard of hypertension at the end of 20th month.4. All offspring of LPS group showed heavier body weights at the 2nd month ages, (P<0.05), but have no diffences from 4th month to 20th month.5. There were no significant differences in the survival time between LPS and control group (P>0.05).6. There were significant differences in the ability of learning and memory between LPS and control group (P<0.01), this diffence is more significant with the aging.7. Compared with control group, the offspring with prenatal LPS exposure showed remarkably the activation of astrocytes ,decreased number of neurons and density of synaptophysin in CA region of hippocampus, these deficiency was more obvious with the aging.Conlusion1. Prenatal exposure to LPS lead to increases in blood pressure for a long time. The boold pressure of LPS reached the level of hypertention.2. Prenatal exposure to LPS specifically impaired distinct forms of learning and memory and this change is more serious with aging.3. Prenatal exposure to LPS impaired the structure of CA region of hippocampus, increased the expressiong of GFAP and reduced the expression of Synapse in rats offspring.