4.4 Article

Effect of experimental genital mycoplasmosis on gene expression in the fetal brain

Journal

JOURNAL OF REPRODUCTIVE IMMUNOLOGY
Volume 93, Issue 1, Pages 9-16

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.jri.2011.11.005

Keywords

Preterm birth; Infection; Cerebral palsy; Neurodevelopmental disorders; Autism

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Neurodevelopmental disorders may have their origins during intrauterine development. We used a well-defined animal model to test whether hematogenous infection with genital mycoplasma would alter the expression of genes associated with autism spectrum disorders (ASD). In a preliminary experiment, rats were exposed at 14 days gestation (GD14) to Mycoplasma pulmonis or sterile broth and sacrificed at GD18. Infection and inflammation status of the pups was ascertained by culture and cytokine ELISA. Intra-cardiac injection of 10(6) CFU M. pulmonis resulted in amniotic infection of 100% of the pups and was accompanied by higher levels of IL-1 beta in amniotic fluids. In a second experiment, animals were infected in a similar manner but dams and their litters were sacrificed at GD18, GD21 or postpartum day 3 (PPD3). Expression of proinflammatory cytokines and neurodevelopmental genes in the fetal brains was evaluated. M. pulmonis infection significantly increased the expression of IL-1 beta, TNF-alpha and COX-2 in fetal and neonatal brains. Expression of GFAP and CD11b, markers for activation on astrocytes and microglial cells, respectively, was also increased for infected animals. M. pulmonis significantly increased SHANK-3 gene expression at GD21 and PPD3 and PCP-2 expression at GD21. No effect of M. pulmonis infection on Reelin. PTEN, BDNF or HGF was detected. These data suggest that M. pulmonis infection at GD14 increases the expression of proinflammatory genes in the perinatal brain. Further studies with earlier time-points of infection and ones that use behavioral outcomes are needed to better understand the potential role of genital mycoplasmosis on pychopathology. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

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