Perinatal exposure to PTU decreases expression of Arc, Homer 1, Egr 1 and Kcna 1 in the rat cerebral cortex and hippocampus.
Environmental chemicals have a potential impact on neuronal development and children's health. The current developmental neurotoxicity (DNT) guideline studies to assess their underlying risk are costly and time-consuming; therefore the more efficient protocol for DNT test is needed. Hypothyroidism in rats induced by perinatal exposure to propylthiouracil (PTU), a thyroid hormone synthesis inhibitor, offers an advantageous model of developmental neurotoxicity (DNT). Understanding the associated alterations in gene expression in brain is a key to elucidate mechanisms and find appropriate molecular markers. The purpose of the present study was to identify PTU treatment-affected transcriptomes in the rat cerebral cortex and the hippocampus using DNA microarrays, and to specify candidate genes linked to DNT. We used an approximately 9000 probe microarray to examine differentially expressed genes between PTU-dosed and vehicle-dosed rats at postnatal days 4, 14, 22 and 70. Expression of immediate early genes (IEGs) such as activity-regulated cytoskeleton-associated protein (Arc), Homer 1, early growth response 1 (Egr 1), myelin-associated genes such as myelin-associated oligodendrocytic basic protein (MOBP), myelin basic protein (MBP) and proteolipid protein (PLP) and Kcna1 was apparently affected by perinatal administration of PTU. The results suggest that the alterations may be responsible for the detrimental effects caused by PTU treatment on the nervous system.
Kobayashi
Kumiko
K
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd. 3-1-98 Kasugade-Naka, Konohana-Ku, Osaka 554-8558, Japan. kobayashik7@sc.sumitomo-chem.co.jp
Akune
Haruyo
H
Sumida
Kayo
K
Saito
Koichi
K
Yoshioka
Takafumi
T
Tsuji
Ryozo
R
D000818:Animals; D000831:Animals, Newborn; D013956:Antithyroid Agents / Q000633:toxicity; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D000072233:Homer Scaffolding Proteins; D007037:Hypothyroidism / Q000139:chemically induced; D051662:Kv1.1 Potassium Channel / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011441:Propylthiouracil / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism
D013956:Antithyroid Agents; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D000072233:Homer Scaffolding Proteins; C489293:Kcna1 protein, rat; C436006:Mbp protein, rat; C560486:Mobp protein, rat; C571328:Mog protein, rat; D009124:Muscle Proteins; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; C491788:Nol3 protein, rat; C489071:Plp1 protein, rat; D012333:RNA, Messenger; D014157:Transcription Factors; D051662:Kv1.1 Potassium Channel; D011441:Propylthiouracil