期刊
NEUROSCIENCE LETTERS
卷 487, 期 2, 页码 199-203出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2010.10.022
关键词
TR; Adult neurogenesis; Subgranular zone; Dentate gyrus; BrdU
资金
- TIFR
- Wellcome Trust Senior Overseas Fellowship in Biomedical Sciences [04082003114133]
- Swedish Research Council
- Swedish Cancer Society
- Wallenberg Foundations
Adult hippocampal neurogenesis is modulated by perturbations in thyroid hormone status; however the role of specific thyroid hormone receptors (TRs) in this process is not completely understood. We show here that loss of the TR beta gene results in a significant increase in the proliferation of adult hippocampal progenitors, without any change in immature neuron number or in the neuronal and glial differentiation of progenitors. Using the mitotic marker 5'-bromo-2-deoxyuridine (BrdU) or the endogenous cell cycle marker, proliferating cell nuclear antigen (PCNA), we find a significant increase in the number of BrdU- and PCNA-immunopositive cells within the subgranular zone (SGZ) of the dentate gyrus subfield in TR beta-/- mice. Further, we find that TR beta mice exhibit a significant increase in the numbers of NeuroD-positive cells within the SGZ, suggesting that the increased numbers of proliferating progenitors translate into enhanced numbers of neuroblasts. Interestingly, the number of BrdU-positive cells that persist 4 weeks post-BrdU injection is unaltered in TR beta-/- mice, indicating that the enhanced proliferation does not result in increased hippocampal neurogenesis. This is also supported by the evidence of no change in the numbers of cells expressing markers of immature neurons such as doublecortin or polysialylated neural cell adhesion molecule. Furthermore, no change is observed in the neuronal or glial differentiation of BrdU-positive cells in the TR beta-/- mice. Taken together, our results provide novel evidence for a role of TR beta in modulating hippocampal progenitor cell division, and implicate this receptor in the effects of thyroid hormone on adult hippocampal neurogenesis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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