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Abstract:

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.

Registro:

Documento: Artículo
Título:Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFβ1 downregulation
Autor:Graciarena, M.; Depino, A.M.; Pitossi, F.J.
Filiación:Laboratory of Regenerative and Protective Therapies of the Nervous System, Foundation Leloir Institute, IIBBA-CONICET, 435 Av Patricias Argentinas, (1405) Buenos Aires, Argentina
Department of Physiology, Molecular and Cellular Biology, Faculty of Exact and Natural Sciences, University of Buenos Aires, (1428) Buenos Aires, Argentina
Palabras clave: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
Año:2010
Volumen:24
Número:8
Página de inicio:1301
Página de fin:1309
DOI: http://dx.doi.org/10.1016/j.bbi.2010.06.005
Título revista:Brain, Behavior, and Immunity
Título revista abreviado:Brain Behav. Immun.
ISSN:08891591
CODEN:BBIME
CAS:Antimetabolites; Bromodeoxyuridine, 59-14-3; Cytokines; Lipopolysaccharides; RNA, 63231-63-0; Transforming Growth Factor beta1; beta-Galactosidase, 3.2.1.23
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08891591_v24_n8_p1301_Graciarena

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Citas:

---------- APA ----------
Graciarena, M., Depino, A.M. & Pitossi, F.J. (2010) . Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFβ1 downregulation. Brain, Behavior, and Immunity, 24(8), 1301-1309.
http://dx.doi.org/10.1016/j.bbi.2010.06.005
---------- CHICAGO ----------
Graciarena, M., Depino, A.M., Pitossi, F.J. "Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFβ1 downregulation" . Brain, Behavior, and Immunity 24, no. 8 (2010) : 1301-1309.
http://dx.doi.org/10.1016/j.bbi.2010.06.005
---------- MLA ----------
Graciarena, M., Depino, A.M., Pitossi, F.J. "Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFβ1 downregulation" . Brain, Behavior, and Immunity, vol. 24, no. 8, 2010, pp. 1301-1309.
http://dx.doi.org/10.1016/j.bbi.2010.06.005
---------- VANCOUVER ----------
Graciarena, M., Depino, A.M., Pitossi, F.J. Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFβ1 downregulation. Brain Behav. Immun. 2010;24(8):1301-1309.
http://dx.doi.org/10.1016/j.bbi.2010.06.005