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Endocrine Unit, Department of Clinical Physiopathology, Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies’ (DENOThe), University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy¹ Department of Haematology, Careggi Hospital, 50139 Florence, Italy Departments of² , Physiological Sciences³ Anatomy, Histology, and Forensic Medicine, University of Florence, 50139 Florence, Italy⁴ Section of Endocrinology, Department of Endocrinology and Metabolism, AMBISEN Center, High Technology Center for the Study of the Environmental Damage of the Endocrine and Nervous Systems, University of Pisa, 56100 Pisa, Italy

(Correspondence should be addressed to A Peri; Email: a.peri{at}dfc.unifi.it)

^* (S Benvenuti and P Luciani equally contributed to this work)

Thyroid hormones (TH) play an important role in the development of human brain, by regulating the expression of specific genes. Selective Alzheimer's disease indicator-1 (seladin-1) is a recently discovered gene with neuroprotective properties, which has been found to be down-regulated in brain regions affected by Alzheimer's disease. Seladin-1 has anti-apoptotic properties mainly due to the inhibition of the activation of caspase 3. The aim of this study was to determine whether seladin-1 may be regarded as a new mediator of the effects of TH in the developing brain. In order to demonstrate this hypothesis, the effects of TH both on cell differentiation and on the expression of seladin-1 were assessed in two different cell models, i.e. fetal human neuroepithelial cells (FNC) and human mesenchymal stem cells (hMSC), which can be differentiated into neurons. 3,3',5-Triiodothyronine (T₃) determined different biological responses (inhibition of cell adhesion, induction of migration, and increase in the expression of the neuronal marker neurofilament-M and Na⁺ and Ca²⁺ channel functionality) in both FNC and hMSC, which express TH receptors. Then, we showed that TH significantly increase the expression levels of seladin-1, and that T₃ effectively prevents camptothecin-induced apoptosis. However, in hMSC-derived neurons the expression of seladin-1 was not affected by TH. Our results demonstrated for the first time that seladin-1 is a novel TH-regulated gene in neuronal precursors. In view of its anti-apoptotic activity, it might be hypothesized that one of the functions of the increased seladin-1 levels in the developing brain may be to protect neuronal precursor cells from death.