ONTOGENIC CHANGES IN THE EXPRESSION OF CYTOCHROME-C-OXIDASE SUBUNIT-IGENE IN THE CEREBELLAR CORTEX OF THE PERINATAL HYPOTHYROID RAT

The thyroid hormone plays a critical role in normal development of the mammalian central nervous system. This study was designed to examine the effect of perinatal hypothyroidism on ontogenic change in cytochro me c oxidase subunit I (COX I) gene expression in the rat cerebellum b y using quantitative in situ hybridization histochemistry (ISH). Newbo rn rats were rendered hypothyroid by continuous administration of meth imazole in the mothers' drinking water. The pups were then killed by d ecapitation on 1, 5, 10, 15, 20, and 30 days after birth (P1, P5, P10, P15, P20, and P30). Their cerebella were removed, and frozen sections were cut and processed for ISH with S-35-labeled RNA probe for COX I messenger RNA, After hybridization, emulsion autoradiography was perfo rmed. The numbers of grains within the external granule cell layer, mo lecular layer, and internal granule cell layer were then counted. A si gnificant decrease in grain density was detected in the hypothyroid an imal in all these areas on P5, P10, and P15. On P15, in the molecular layer, a greater hybridization signal was detected in the inner portio n than in the outer potion in the euthyroid animal. No such difference was seen in the hypothyroid animal. Daily T-4 treatment for 15 days r estored the effect of methimazole treatment. The significant effect of perinatal hypothyroidism on COX I gene expression was not detected af ter P20. These results indicate that altered thyroid states affect the COX I gene expression in the cerebellar cortex during development, su ggesting that the COX I gene is one of the key genes regulated by the thyroid hormone and plays an important role in the morphogenetic chang es observed in the perinatal hypothyroid cerebellum.