PMID- 23475384 OWN - NLM STAT- MEDLINE DCOM- 20140303 LR - 20211021 IS - 1473-4230 (Electronic) IS - 1473-4222 (Linking) VI - 12 IP - 4 DP - 2013 Aug TI - Effects of perinatal lipopolysaccharide (LPS) exposure on the developing rat brain; modeling the effect of maternal infection on the developing human CNS. PG - 572-86 LID - 10.1007/s12311-013-0465-z [doi] AB - In the present study, we examined the effect of perinatal Escherichia coli lipopolysaccharide (LPS) exposure on the developing rat cerebellum and tested the hypothesis that maternal infections impact brain structure and function by mechanisms involving increase in oxidative stress and changes in brain type 2 iodothyronine deiodinase (D2)- and thyroid hormone (TH)-responsive genes. Spontaneously hypertensive rat (SHR) and Sprague-Dawley (SD) rat dams were challenged with LPS (200 mug/kg body weight) exposure during pregnancy (G10-G15) and lactation (P5-P10), the time periods corresponding, respectively, to the first/second and the third trimesters of human pregnancy. LPS exposure resulted in a significantly decreased motor learning in SD male (29.8 %) and in female (55.0 %) pups (p < 0.05); changes in rollover and startle response showed only a trend. The LPS challenge also resulted in a trend (p = 0.09) toward increased cerebellar levels of the oxidative stress marker 3-nitrotyrosine (3-NT) in SD male (16.2 %) and female (21.2 %) neonates, while 3-NT levels were significantly decreased (p < 0.05) in SHR female pups. D2 activity, responsible for local intra-brain conversion of thyroxine (T4) to the active hormone, 3',3,5-triiodothyronine (T3), was significantly (p < 0.05) decreased in LPS-challenged SHR male (40.3 %) and SD female (47.4 %) pups. Several genes were affected by LPS. Notably, D2 (DIO2) and brain-derived neurotrophic factor (BDNF) were significantly elevated in SHR females, while transthyretin (TTR) expression was decreased in both SD males and females (P < 0.05). In vitro chronic exposure of cerebellar cultures to LPS resulted in decreased arborization of Purkinje cells while D2 was only increased transiently. Our data demonstrate that perinatal LPS exposure impacts the developing cerebellum in strain- and sex-dependent manner via complex mechanisms that involve changes in oxidative stress, enzymes involved in maintaining local TH homeostasis, and downstream gene expression. FAU - Xu, M AU - Xu M AD - Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. FAU - Sulkowski, Z L AU - Sulkowski ZL FAU - Parekh, P AU - Parekh P FAU - Khan, A AU - Khan A FAU - Chen, T AU - Chen T FAU - Midha, S AU - Midha S FAU - Iwasaki, T AU - Iwasaki T FAU - Shimokawa, N AU - Shimokawa N FAU - Koibuchi, N AU - Koibuchi N FAU - Zavacki, A M AU - Zavacki AM FAU - Sajdel-Sulkowska, E M AU - Sajdel-Sulkowska EM LA - eng GR - 096646/Wellcome Trust/United Kingdom GR - DK76117/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Cerebellum JT - Cerebellum (London, England) JID - 101089443 RN - 0 (Lipopolysaccharides) SB - IM MH - Animals MH - Animals, Newborn MH - Bacterial Infections/chemically induced/metabolism MH - Cells, Cultured MH - Cerebellum/drug effects/*growth & development/*metabolism MH - *Disease Models, Animal MH - Female MH - Humans MH - Lipopolysaccharides/*toxicity MH - Male MH - Oxidative Stress/drug effects/physiology MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*chemically induced/*metabolism MH - Rats MH - Rats, Inbred SHR MH - Rats, Sprague-Dawley MH - Sex Factors MH - Species Specificity EDAT- 2013/03/12 06:00 MHDA- 2014/03/04 06:00 CRDT- 2013/03/12 06:00 PHST- 2013/03/12 06:00 [entrez] PHST- 2013/03/12 06:00 [pubmed] PHST- 2014/03/04 06:00 [medline] AID - 10.1007/s12311-013-0465-z [doi] PST - ppublish SO - Cerebellum. 2013 Aug;12(4):572-86. doi: 10.1007/s12311-013-0465-z.