Thyroid hormones (TH) play a fundamental role during brain development by modulating the expression of different genes involved in neuronal differentiation, proliferation, migration, myelinization, and synapse formation. Seladin-1 (for SELective Alzheimers Disease INdicator-1) is a recently identified anti-apoptotic gene, which has been found to be down-regulated in brain regions affected by Alzheimers disease (AD). We hypothesized that seladin-1 might be a novel mediator of the effects of TH in the developing brain. Thus, in the present study we determined whether TH modulate the expression of seladin-1 in human neuronal precursors and/or in differentiated cells. Two different cell models were used: fetal human neuroepithelial cells (FNC) isolated previously from fetal olfactory epithelium; and human mesenchymal stem cells (hMSC), isolated from bone marrow, which have a demonstrated ability to differentiate into neurons. In our hands, hMSC were differentiated into neurons (hMSC-n), following previously established protocols. The neuronal phenotype was confirmed by the positivity for the specific markers nestin, glypican 4, necdin, neurofilament subunit L, neurofilament subunit M, neurite outgrowth-promoting protein, choline acetyltransferase, neuronal nuclei. Electrophysiological evaluation revealed the presence of inward Na and Ca currents typical of neuronal cells. In basal conditions, the amount of seladin-1 was significantly higher in undifferentiated cells than in mature neurons, as assessed by real-time RT-PCR. T3 and T4 (1 nM) significantly increased the amount of seladin-1 mRNA in both FNC (140% and 66% increase, respectively) and hMSC (61% and 16% increase, respectively), but not in hMSC-n. The amount of the protein, evaluated by Western blotting, changed accordingly. This is the first demonstration that TH stimulate the expression of seladin-1 in human neuronal precursors, but not in terminally differentiated neurons. These results suggest that this neuroprotective factor may play a prevalent role during brain development, together with other well-known TH-dependent factors.
28 Apr - 02 May 2007
European Society of Endocrinology