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Neonatal impact of leukemia inhibitory factor on neurobehavioral development in rats

Watanabe, Yuichiro and Hashimoto, Shinya and Kakita, Akiyoshi and Takahashi, Hitoshi and Ko, Jan and Mizuno, Makoto and Someya, Toshiyuki and Patterson, Paul H. and Nawa, Hiroyuki (2004) Neonatal impact of leukemia inhibitory factor on neurobehavioral development in rats. Neuroscience Research, 48 (3). pp. 345-353. ISSN 0168-0102. doi:10.1016/j.neures.2003.12.001.

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Cytokines have been implicated in the etiology or pathology of various psychiatric diseases of developmental origin such as autism and schizophrenia. Leukemia inhibitory factor (LIF) is induced by a variety of brain insults and known to have many influences on mature and immature nervous system. Here, we assessed the neurobehavioral and pathological consequences of peripheral administration of LIF in newborn rats. Subcutaneous LIF injection induced STAT3 phosphorylation in many brain regions and increased glial fibrillary acidic protein (GFAP) immunoreactivity in the neocortex, suggesting that LIF had direct effects in the central nervous system. The LIF-treated rats displayed decreased motor activity during juvenile stages, and developed abnormal prepulse inhibition in the acoustic startle test during and after adolescence. They displayed normal learning ability in active avoidance test, however. Brain neuronal structures and startle responses were grossly normal, except for the cortical astrogliosis during neonatal LIF administration. These results indicate that LIF induction in the periphery of the infant has a significant, but discrete impact on neurobehavioral development.

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Additional Information:© 2003 Elsevier Ireland Ltd and The Japan Neuroscience Society. Received 30 August 2003; accepted 4 December 2003. We thank Dr. M. Tohmi, Dr. H. Sotoyama and Dr. S. Qi for technical assistance. This work was supported by Health Science Research Grant for Research on Human Genome and Regenerative Medicine from Ministry of Health, Labour and Welfare of Japan (TS), a grant-in-aid for Creative Scientific Research (HN), a grant-in-aid for Cancer Research (HN), the McGrath Foundation (PHP) and the Gimble Discovery Fund in Neuroscience (PHP).
Funding AgencyGrant Number
Ministry of Health, Labour and Welfare (Japan)UNSPECIFIED
McGrath FoundationUNSPECIFIED
Gimble Discovery FundUNSPECIFIED
Subject Keywords:LIF; Oncostatin M; CNTF; Astrocyte; Schizophrenia; Autism; PPI
Issue or Number:3
Record Number:CaltechAUTHORS:20160122-105357784
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Official Citation:Yuichiro Watanabe, Shinya Hashimoto, Akiyoshi Kakita, Hitoshi Takahashi, Jan Ko, Makoto Mizuno, Toshiyuki Someya, Paul H Patterson, Hiroyuki Nawa, Neonatal impact of leukemia inhibitory factor on neurobehavioral development in rats, Neuroscience Research, Volume 48, Issue 3, March 2004, Pages 345-353, ISSN 0168-0102, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:63896
Deposited By: Ruth Sustaita
Deposited On:25 Jan 2016 17:27
Last Modified:10 Nov 2021 23:22

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