| First Author | Kapoor R | Year | 2010 |
| Journal | FASEB J | Volume | 24 |
| Issue | 12 | Pages | 4793-805 |
| PubMed ID | 20709911 | Mgi Jnum | J:166374 |
| Mgi Id | MGI:4844208 | Doi | 10.1096/fj.10-161802 |
| Citation | Kapoor R, et al. (2010) Unliganded thyroid hormone receptor {alpha}1 impairs adult hippocampal neurogenesis. FASEB J 24(12):4793-805 |
| abstractText | Thyroid hormone regulates adult hippocampal neurogenesis, a process involved in key functions, such as learning, memory, and mood regulation. We addressed the role of thyroid hormone receptor TRalpha1 in adult hippocampal neurogenesis, using mice harboring a TRalpha1 null allele (TRalpha1(-/-)), overexpressing TRalpha1 6-fold (TRalpha2(-/-)), and a mutant TRalpha1 (TRalpha1(+/m)) with a 10-fold lower affinity to the ligand. While hippocampal progenitor proliferation was unaltered, TRalpha1(-/-) mice exhibited a significant increase in doublecortin-positive immature neurons and increased survival of bromodeoxyuridine-positive (BrdU(+)) progenitors as compared to wild-type controls. In contrast, the TRalpha1(+/m) and the TRalpha2(-/-) mice, where the overexpressed TRalpha1 acts as an aporeceptor, showed a significant decline in surviving BrdU(+) progenitors. TRalpha1(-/-) and TRalpha2(-/-) mice showed opposing effects on neurogenic markers like polysialylated neural cell adhesion molecule and stathmin. The decreased progenitor survival in the TRalpha2(-/-) and TRalpha1(+/m) mice could be rescued by thyroid hormone treatment, as was the decline in neuronal differentiation seen in the TRalpha1(+/m) mice. These mice also exhibited a decrease in NeuroD(+) cell numbers in the dentate gyrus, suggesting an effect on early postmitotic progenitors. Our results provide the first evidence of a role for unliganded TRalpha1 in modulating the deleterious effects of hypothyroidism on adult hippocampal neurogenesis.-Kapoor, R., van Hogerlinden, M., Wallis, K., Ghosh, H., Nordstrom, K., Vennstrom, B., Vaidya, V. A. Unliganded thyroid hormone receptor alpha1 impairs adult hippocampal neurogenesis. |
