Loss of thyroid hormone receptor β is associated with increased progenitor proliferation and NeuroD positive cell number in the adult hippocampus.
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 TRβ 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 TRβ-/- mice. Further, we find that TRβ-/- 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 TRβ-/- 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 TRβ-/- mice. Taken together, our results provide novel evidence for a role of TRβ in modulating hippocampal progenitor cell division, and implicate this receptor in the effects of thyroid hormone on adult hippocampal neurogenesis.
Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
Richa
R
Kapoor
Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
Himanish
H
Ghosh
Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Kristina
K
Nordstrom
Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Björn
B
Vennstrom
Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
Vidita A
VA
Vaidya
D000367:Age Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002452:Cell Count / Q000379:methods; D002455:Cell Division / Q000502:physiology; D049109:Cell Proliferation; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000378:metabolism*; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000172:deficiency* / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D037042:Thyroid Hormone Receptors beta; C093564:Neurogenic differentiation factor 1