Regulation of microglial development: A novel role for thyroid hormone

The postnatal development of rat microglia is marked by an important increa se in the number of microglial cells and the growth of their ramified proce sses. We studied the role of thyroid hormone in microglial development. The distribution and morphology of microglial cells stained with isolectin B4 or monoclonal antibody ED1 were analyzed in cortical and subcortical forebr ain regions of developing rats rendered hypothyroid by prenatal and postnat al treatment with methyl-thiouracil. Microglial processes were markedly les s abundant in hypothyroid pups than in age-matched normal animals, from pos tnatal day 4 up to the end of the third postnatal week of life. A delay in process extension and a decrease in the density of microglial cell bodies, as shown by cell counts in the developing cingulate cortex of normal and hy pothyroid animals, were responsible for these differences. Conversely, neon atal rat hyperthyroidism, induced by daily injections of 3,5,3'-triiodothyr onine (T3), accelerated the extension of microglial processes and increased the density of cortical microglial cell bodies above physiological levels during the first postnatal week of life. Reverse transcription-PCR and immunological analyses indicated that culture d cortical ameboid microglial cells expressed the alpha1 and beta1 isoforms of nuclear thyroid hormone receptors. Consistent with the trophic and morp hogenetic effects of thyroid hormone observed in situ, T3 favored the survi val of cultured purified microglial cells and the growth of their processes . These results demonstrate that thyroid hormone promotes the growth and mo rphological differentiation of microglia during development.