title: Prenatal exposure to bacterial endotoxin reduces the number of GAD67- and reelin-immunoreactive neurons in the hippocampus of rat offspring.
abstract: Epidemiological studies implicate prenatal infection as a risk factor for the development of schizophrenia and autism. Subjects with schizophrenia and autism are reported to exhibit reduced levels of glutamic acid decarboxylase 67 (GAD67), a marker for GABA neurons, in various brain regions. Reduced levels of reelin, a secretory glycoprotein present in a subpopulation of GABA neurons, have also been found in these disorders. To test if prenatal infection can cause abnormalities in GAD67 and reelin in the brains of offspring, this study used a rat model of prenatal exposure to the bacterial endotoxin, lipopolysaccharide (LPS), and assessed numbers of GAD67-immunoreactive (GAD67+) and reelin-immunoreactive (reelin+) neurons in the hippocampus of offspring. In offspring at postnatal day 14 (PD14), GAD67+ cell counts were reduced in the dentate gyrus of the prenatal LPS group compared to prenatal saline controls, while at PD28, GAD67+ cells counts were reduced in the prenatal LPS group in both the dentate gyrus and the CA1. There was a decrease in the number of reelin+ cells in the prenatal LPS offspring compared to controls in the dentate gyrus at PD14. However using Western blotting, no significant effects of prenatal LPS on levels of GAD67 or reelin protein were observed in various brain regions at PD14. These findings support the idea that prenatal infection can cause reductions in postnatal expression of GAD67 and reelin, and in this way, possibly contribute to the pathophysiology of schizophrenia or autism.
authors: Department of Psychiatry, McGill University, Douglas Mental Health University Institute, Montreal, Canada.
authors: Dominique
authors: D
authors: Nouel
authors: Melissa
authors: M
authors: Burt
authors: Ying
authors: Y
authors: Zhang
authors: Louise
authors: L
authors: Harvey
authors: Patricia
authors: P
authors: Boksa
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002452:Cell Count / Q000706:statistics & numerical data; D018891:Dentate Gyrus / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717129:Reln protein, rat; C000717127:RELN protein, human; D012697:Serine Endopeptidases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1