Perinatal exposure to PTU decreases expression of Arc , Homer 1 , Egr 1 and Kcna 1 in the rat cerebral cortex and hippocampus

• Published in: Brain research Vol. 1264; pp. 24 - 32
• Main Authors: Kobayashi, Kumiko, Akune, Haruyo, Sumida, Kayo, Saito, Koichi, Yoshioka, Takafumi, Tsuji, Ryozo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 06.04.2009; Elsevier
• Subjects: Animals; Animals, Newborn; Antithyroid Agents - toxicity; Apoptosis Regulatory Proteins - metabolism; Biochemistry and metabolism; Biological and medical sciences; Carrier Proteins - metabolism; Central nervous system; Cerebral Cortex - drug effects; Cerebral Cortex - growth & development; Cerebral Cortex - metabolism; Disease Models, Animal; DNA microarray; Early Growth Response Protein 1 - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression and Developmental neurotoxicity; Gene Expression Regulation - drug effects; Genes, Immediate-Early - drug effects; Hippocampus - drug effects; Hippocampus - growth & development; Hippocampus - metabolism; Homer Scaffolding Proteins; Hypothyroidism - chemically induced; Kv1.1 Potassium Channel - metabolism; Male; Muscle Proteins - metabolism; Myelin Basic Protein; Myelin Proteins; Myelin Proteolipid Protein - metabolism; Myelin-Associated Glycoprotein - metabolism; Myelin-Oligodendrocyte Glycoprotein; Nerve Tissue Proteins - metabolism; Neurology; Oligonucleotide Array Sequence Analysis; Propylthiouracil; Propylthiouracil - toxicity; Quantitative Real-Time PCR; Rats; RNA, Messenger - metabolism; Transcription Factors - metabolism; Vertebrates: nervous system and sense organs; DNA microarray; Propylthiouracil; Gene expression and Developmental neurotoxicity; Quantitative Real-Time PCR; Gene expression and Developmental; Cerebral cortex; Rat; Rodentia; Central nervous system; DNA chip; Perinatal; Gene expression; Encephalon; Polymerase chain reaction; Vertebrata; Neurotoxicity; Mammalia; Animal; EGR1 transcription factor; Development; Thyroid hormone; Inhibitor; Hippocampus
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.12.029

Abstract 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.