| Abstract No.: | A-C1114 |
| Country: | Canada |
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| Title: | EFFECTS OF PRENANAL INFECTION ON NEUROGENESIS IN THE HIPPOCAMPAL DENTATE GYRUS |
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| Authors/Affiliations: | 1 Ke CUI*; 1 Giamal N Luheshi; 1 Patricia Boksa;
1 Mental Health University Institute, Montreal, QC, Canada
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| Content: | Background: Maternal infection during pregnancy has been associated with increased risk for schizophrenia in offspring. Many studies indicate that the hippocampus has a critical role in the neuropathology and pathophysiology of schizophrenia. Neurogenesis in the hippocampal dentate gyrus occurs perinatally and has been shown to continue during adult life and affect hippocampal performance.
Objective: To test the hypothesis that maternal infection during pregnancy affects neurogenesis in the hippocampus of offspring, using an animal model. Materials and Methods: The bacterial endotoxin, lipolysaccharide (LPS), was administered intraperitoneally (i.p.) to pregnant rats to mimic maternal infection. Control pregnant rats were injected with saline. LPS or saline was given to the dam (treated or control) once daily on day 15 and 16 (mid gestation) or day 18 and 19 (late gestation) of pregnancy. To determine if hippocampal neurogenesis in offspring is affected by the prenatal infection, bromodeoxyuridine (BrdU), a marker of cell division, was i.p. injected either to the pregnant dams at the time of the infection, or to their male offspring at postnatal day 14, 21 or 60 (P14, P21 or P60). Male offspring were transcardially perfused either two hours after BrdU injection to assess cell proliferation, or four weeks after BrdU injection to assess neuronal survival. Fluorescent immunohistochemistry was performed to identify the newly born cells (BrdU-positive). BrdU-positive cells in the dentate gyrus were counted at six levels representing the anterior, middle and posterior hippocampus. Double fluorescent labelling with BrdU and the neuronal marker, NeuN, was used to assess the differentiation of newly born cells into neurons.
Results: LPS administration during mid gestation resulted in a significant decrease in hippocampal cell proliferation in 14 day old offspring, compared to controls. In addition, the number of newborn cells that survived for four weeks following BrdU injection at P14 was also significantly decreased in pups from treated compared to control dams. When maternal infection was induced during late gestation, survival of hippocampal cells that had been newly born either at the time of the maternal infection or at P14 was significantly decreased in pups from treated compared to control dams. Most of the newborn cells differentiated into neurons in all the groups.
Conclusions: In rat offspring exposed to prenatal infection either at mid or late gestation, we observed abnormal neurogenesis in the hippocampal dentate gyrus during early postnatal life. These findings support the idea that maternal infection during pregnancy may have deleterious effects on hippocampal development in offspring.
Supported by the Canadian Institutes of Health Research, the Canadian Psychiatric Research Foundation, and AstraZeneca Canada.
All procedures were performed in accordance with the guidelines established by the Canadian Council on Animal Care and were approved by the McGill University Animal Care Committee.
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