Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFβ1 downregulation
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 ad...
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2010
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paper:paper_08891591_v24_n8_p1301_Graciarena2023-06-08T15:47:04Z Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFβ1 downregulation Cytokines Inflammation Learning and memory Neurogenesis Neurogenic niche Prenatal programming lipopolysaccharide transforming growth factor beta1 adulthood animal experiment animal tissue article behavior brain nerve cell cell proliferation dentate gyrus down regulation embryo female gene overexpression hippocampus inflammation macrophage activation male maternal behavior memory microglia nervous system development newborn nonhuman pregnancy prenatal exposure priority journal progeny rat recognition short term memory Adenoviridae Animals Antimetabolites Behavior, Animal beta-Galactosidase Bromodeoxyuridine Cell Proliferation Cytokines Down-Regulation Female Genetic Vectors Hippocampus Lipopolysaccharides Macrophage Activation Maternal Behavior Memory Microglia Neurogenesis Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Wistar Recognition (Psychology) RNA Transforming Growth Factor beta1 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 (TGFβ1) occurred specifically in the adult hippocampus of animals treated prenatally with LPS. Importantly, chronic hippocampal TGFβ1 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 (TGFβ1) in the hippocampus can restore adult neurogenesis and its related behavior, highlighting the role of TGFβ1 in these processes. © 2010 Elsevier Inc. 2010 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08891591_v24_n8_p1301_Graciarena http://hdl.handle.net/20.500.12110/paper_08891591_v24_n8_p1301_Graciarena |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Cytokines Inflammation Learning and memory Neurogenesis Neurogenic niche Prenatal programming lipopolysaccharide transforming growth factor beta1 adulthood animal experiment animal tissue article behavior brain nerve cell cell proliferation dentate gyrus down regulation embryo female gene overexpression hippocampus inflammation macrophage activation male maternal behavior memory microglia nervous system development newborn nonhuman pregnancy prenatal exposure priority journal progeny rat recognition short term memory Adenoviridae Animals Antimetabolites Behavior, Animal beta-Galactosidase Bromodeoxyuridine Cell Proliferation Cytokines Down-Regulation Female Genetic Vectors Hippocampus Lipopolysaccharides Macrophage Activation Maternal Behavior Memory Microglia Neurogenesis Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Wistar Recognition (Psychology) RNA Transforming Growth Factor beta1 |
| spellingShingle |
Cytokines Inflammation Learning and memory Neurogenesis Neurogenic niche Prenatal programming lipopolysaccharide transforming growth factor beta1 adulthood animal experiment animal tissue article behavior brain nerve cell cell proliferation dentate gyrus down regulation embryo female gene overexpression hippocampus inflammation macrophage activation male maternal behavior memory microglia nervous system development newborn nonhuman pregnancy prenatal exposure priority journal progeny rat recognition short term memory Adenoviridae Animals Antimetabolites Behavior, Animal beta-Galactosidase Bromodeoxyuridine Cell Proliferation Cytokines Down-Regulation Female Genetic Vectors Hippocampus Lipopolysaccharides Macrophage Activation Maternal Behavior Memory Microglia Neurogenesis Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Wistar Recognition (Psychology) RNA Transforming Growth Factor beta1 Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFβ1 downregulation |
| topic_facet |
Cytokines Inflammation Learning and memory Neurogenesis Neurogenic niche Prenatal programming lipopolysaccharide transforming growth factor beta1 adulthood animal experiment animal tissue article behavior brain nerve cell cell proliferation dentate gyrus down regulation embryo female gene overexpression hippocampus inflammation macrophage activation male maternal behavior memory microglia nervous system development newborn nonhuman pregnancy prenatal exposure priority journal progeny rat recognition short term memory Adenoviridae Animals Antimetabolites Behavior, Animal beta-Galactosidase Bromodeoxyuridine Cell Proliferation Cytokines Down-Regulation Female Genetic Vectors Hippocampus Lipopolysaccharides Macrophage Activation Maternal Behavior Memory Microglia Neurogenesis Pregnancy Prenatal Exposure Delayed Effects Rats Rats, Wistar Recognition (Psychology) RNA Transforming Growth Factor beta1 |
| description |
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 (TGFβ1) occurred specifically in the adult hippocampus of animals treated prenatally with LPS. Importantly, chronic hippocampal TGFβ1 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 (TGFβ1) in the hippocampus can restore adult neurogenesis and its related behavior, highlighting the role of TGFβ1 in these processes. © 2010 Elsevier Inc. |
| title |
Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFβ1 downregulation |
| title_short |
Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFβ1 downregulation |
| title_full |
Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFβ1 downregulation |
| title_fullStr |
Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFβ1 downregulation |
| title_full_unstemmed |
Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFβ1 downregulation |
| title_sort |
prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal tgfβ1 downregulation |
| publishDate |
2010 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08891591_v24_n8_p1301_Graciarena http://hdl.handle.net/20.500.12110/paper_08891591_v24_n8_p1301_Graciarena |
| _version_ |
1768543710103994368 |