title: Developmental changes in hypothalamic toll-like-receptor 4 mRNA expression and the effects of lipopolysaccharide on such changes in female rats.
abstract: Hypothalamic pro-inflammatory cytokine expression exhibits a weaker response to lipopolysaccharides (LPS) during the early neonatal period than during the later developmental period. Although toll-like receptor 4 (TLR4), which recognizes bacterial molecules, activates pro-inflammatory cytokine responses, the developmental changes in hypothalamic TLR4 expression have not been evaluated. In this study, the hypothalamic TLR4 mRNA levels of saline-injected and LPS-injected rats were measured during the neonatal, pre-pubertal, and post-pubertal periods. The rats' hypothalamic TLR4 mRNA levels gradually increased from the neonatal to pubertal period and were altered by the injection of LPS at all examined ages (postnatal day (PND) 5, 15, 25, and 42). LPS injection resulted in decreased hypothalamic TLR4 mRNA expression at PND5, whereas it increased hypothalamic TLR4 mRNA expression at PND15, 25, and 42. After the injection of LPS, the hypothalamic mRNA levels of the pro-inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor α, and IL-6 were attenuated during the early developmental period and increased acutely on PND42. The expression profiles of these pro-inflammatory cytokines exhibited similar, but not entirely consistent, changes to those displayed by TLR4 during the developmental period. Hypothalamic TLR4 mRNA expression gradually increased throughout the developmental period, whereas the mRNA expression levels of the pro-inflammatory cytokines increased acutely at PND42. Thus, it is assumed that hypothalamic TLR4 hypoactivity contributes to the low sensitivity of pro-inflammatory cytokines to LPS during the early developmental period.
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan. Electronic address: iwasa.takeshi@tokushima-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwasa
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Matsuzaki
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Altankhuu
authors.initials: A
authors.lastname: Tungalagsuvd
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Munkhsaikhan
authors.initials: M
authors.lastname: Munkhzaya
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Kawami
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Yamasaki
authors.affiliation: Department of Obstetrics and Gynecology, Shikoku Medical Center for Children and Adults, Senyu-cho 2-1-1, Zentsuji City, Kagawa 765-8507, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kuwahara
authors.affiliation: Department of Reproductive Technology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yasui
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Irahara
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D007031:Hypothalamus / Q000254:growth & development / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4
keywords: Hypothalamus; IL-1β; IL-6; TLR4; TNF-α