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Publication : Loss of thyroid hormone receptor β is associated with increased progenitor proliferation and NeuroD positive cell number in the adult hippocampus.

First Author  Kapoor R Year  2011
Journal  Neurosci Lett Volume  487
Issue  2 Pages  199-203
PubMed ID  20959135 Mgi Jnum  J:168644
Mgi Id  MGI:4889160 Doi  10.1016/j.neulet.2010.10.022
Citation  Kapoor R, et al. (2011) Loss of thyroid hormone receptor beta is associated with increased progenitor proliferation and NeuroD positive cell number in the adult hippocampus. Neurosci Lett 487(2):199-203
abstractText  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 TRbeta 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 TRbeta-/- mice. Further, we find that TRbeta-/- 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 TRbeta-/- 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 TRbeta-/- mice. Taken together, our results provide novel evidence for a role of TRbeta in modulating hippocampal progenitor cell division, and implicate this receptor in the effects of thyroid hormone on adult hippocampal neurogenesis.
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