| Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFβ1 downregulation. | |
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MedLine Citation:
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PMID: 20600816 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Prenatal exposure to inflammatory stimuli is known to influence adult brain function. In addition, adult hippocampal neurogenesis is impaired by a local pro-inflammatory microenvironment. On this basis, we hypothesized that a pro-inflammatory insult during gestation would have negative effects on adult neurogenesis in the offspring. Pregnant Wistar rats received subcutaneous injections of lipopolysaccharide (LPS; 0.5mg/kg) or saline every other day from gestational day 14 to 20. The adult offspring prenatally treated with LPS showed a decrease in the proliferating cells and the newborn neurons of the dentate gyrus. Furthermore, prenatal LPS treatment impaired performance in the neurogenesis-dependent novel object recognition test. Maternal care was impaired by prenatal LPS administration but did not contribute to the effects of prenatal LPS on adult neurogenesis. Persistent microglial activation and downregulated expression of transforming growth factor beta-1 (TGFβ(1)) occurred specifically in the adult hippocampus of animals treated prenatally with LPS. Importantly, chronic hippocampal TGFβ(1) overexpression restored neurogenesis as well as recognition memory performance to control levels. These findings demonstrate that prenatal inflammation triggered by LPS impairs adult neurogenesis and recognition memory. Furthermore, we provide a model of reduced adult neurogenesis with long-lasting defined alterations in the neurogenic niche. Finally, we show that the expression of a single cytokine (TGFβ(1)) in the hippocampus can restore adult neurogenesis and its related behavior, highlighting the role of TGFβ(1) in these processes. |
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Authors:
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Mariana Graciarena; Amaicha M Depino; Fernando J Pitossi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-20 |
Journal Detail:
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Title: Brain, behavior, and immunity Volume: 24 ISSN: 1090-2139 ISO Abbreviation: Brain Behav. Immun. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-04 Completed Date: 2011-01-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8800478 Medline TA: Brain Behav Immun Country: United States |
Other Details:
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Languages: eng Pagination: 1301-9 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Laboratory of Regenerative and Protective Therapies of the Nervous System, Foundation Leloir Institute, IIBBA-CONICET, 435 Av Patricias Argentinas, 1405 Buenos Aires, Argentina. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics Animals Antimetabolites / diagnostic use Behavior, Animal / physiology* Bromodeoxyuridine / diagnostic use Cell Proliferation Cytokines / biosynthesis Down-Regulation / physiology Female Genetic Vectors Hippocampus / cytology, physiology* Lipopolysaccharides / pharmacology Macrophage Activation / physiology Maternal Behavior Memory / physiology* Microglia / physiology Neurogenesis / physiology* Pregnancy Prenatal Exposure Delayed Effects / pathology*, psychology* RNA / biosynthesis, genetics, isolation & purification Rats Rats, Wistar Recognition (Psychology) / physiology Transforming Growth Factor beta1 / biosynthesis*, genetics beta-Galactosidase / biosynthesis, genetics |
| Chemical | |
Reg. No./Substance:
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0/Antimetabolites; 0/Cytokines; 0/Lipopolysaccharides; 0/Transforming Growth Factor beta1; 59-14-3/Bromodeoxyuridine; 63231-63-0/RNA; EC 3.2.1.23/beta-Galactosidase |
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