Tohoku J. Exp. Med., 2011, 223(3)

Maternal Undernutrition with Vaginal Inflammation Impairs the Neonatal Oligodendrogenesis in Mice

TAKUYA ITO,¹ KAORI HOSHIAI,² KAORI TANABE,³ AI NAKAMURA,³ KIYOE FUNAMOTO,³ AYAKO AOYAGI,³ HIROSHI CHISAKA,² KUNIHIRO OKAMURA,⁴ NOBUO YAEGASHI² and YOSHITAKA KIMURA³

¹Innovation of New Biomedical Engineering Center, Tohoku University, Sendai, Japan
²Division of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan
³International Advanced research and Education Organization, Tohoku University, Sendai, Japan
⁴KKR Tohoku Kousai Hospital, Sendai, Japan

Maternal undernutrition and infection during pregnancy may impair development of oligodendrocytes, thereby increasing risks of neuropsychiatric disorders of their children. We analyzed the effects of those risk factors on oligodendrogenesis in fetal and neonatal brains. Female mice were given low-protein or regular food for 2 weeks before their pregnancy. On the 14th day of pregnancy, they received a transvaginal injection of lipopolysaccharide to induce inflammation or control solution, consisting of four groups, depending on nutritional conditions with or without vaginal inflammation. We collected fetal brains on embryonic day (E) 17 for evaluating oligodendrocyte precursor cells (OPCs) and neonatal brains on postnatal day (P) 7 for evaluating mature oligodendrocytes. OPCs and mature oligodendrocytes were identified as positive immunostaining for oligodendrocyte-lineage transcription factor 2 and myelin basic protein, respectively. There was no difference in the number of OPCs in E17 brains among the four groups, suggesting that nutritional restriction with or without inflammation exerts no noticeable influence on the differentiation of OPCs. However, the number of mature oligodendrocytes was decreased in P7 brains obtained from nutrient-restricted mice with inflammation, suggesting that their combination impairs oligodendrogenesis in the neonatal brain. We also analyzed reactive astrocytes that express both glial fibrillary acidic protein and nestin for evaluating brain inflammation. The population of reactive astrocytes was increased in P7 brains derived from mice with LPS injection, irrespective of nutritional restriction, indicating that maternal vaginal inflammation induces neonatal brain inflammation. The maternal management of both nutrition and infection is crucial to prevent neuropsychiatric disorders of the children.

keywords —— undernutrition; intrauterine infection; oligodendrocyte; neuropsychiatric disorders; neonatal period

© 2011 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2011, 223, 215-222

Correspondence: Takuya Ito, Innovation of New Biomedical Engineering Center, Tohoku University, 1-1 Seiryou-machi, Aoba-ku, Sendai 980-8574, Japan.

e-mail: i-takuya@med.tohoku.ac.jp