Thyroid hormone actions on the microglial development

THYROID HORMONE ACTIONS ON THE MICROGLIAL DEVELOPMENT^*

FLAVIA R. SOUZA LIMA^1,2,3, ANNIE GERVAIS¹, VIVALDO MOURA NETO³AND MICHEL MALLAT¹

¹

²Instituto de Biofisica Carlos Chagas Filho

³Department of Anatomy

Federal University of Rio de Janeiro, 21941-590 Rio de Janeiro, RJ, Brazil.

In addition to infiltration of the CNS by mesodermal precursors, the development of microglia requires that these cells survive, proliferate and develop ramified cell processes. These cellular events are most probably controlled by physiological extracellular or diffusible signals which have not been thoroughly characterized. We have looked for a possible role of thyroid hormone (TH). The distribution of microglial cells was analyzed in the forebrain of developing rats rendered hypothyroid by pre- and postnatal treatment with methyl-thiouracil. TH deprivation markedly altered the growth of microglial cells labeled with isolectin B4 or OX-42 monoclonal antibodies. Microglial processes in forebrain regions from hypothyroid pups were less developed than in age-matched normal animals from post-natal day 4 (P4) up to at least P21. Both a delay in processes extension and a decrease in the number of microglial cell bodies, as shown by cell counts in the developing cingulate cortex of normal and hypothyroid animals, were responsible for these differences. Conversely, neonatal hyperthyroidism obtained by daily injection of rat pups with triiodothyronine (T3) accelerated the extension of microglial processes and increased the number of cortical microglial cell bodies above physiological levels, during the first postnatal week of life. In cultures of rat ameboid microglial cells, the effects of T3 on survival and morphology were consistent with the trophic and morphogenetic effects of TH observed in situ. Cultured microglia degenerated when the cells were kept at low cell density in a medium with low or no TH-free serum content. Addition of T3 to the medium significantly reduced microglial degeneration. In addition to its effects on survival, quantitative morphological assessment of cultured cells indicated that T3 stimulated the in vitro growth of microglial processes. RT-PCR and immunological analyses showed that the cultured microglia expressed nuclear TH receptors. Our results demonstrate that TH contributes to the regulation of microglial growth and differentiation during development. — ( June 27, 2000 ).

Publication Dates

• Publication in this collection
  05 Oct 2000
• Date of issue
  Sept 2000