title: Thyroid hormones promote cell differentiation and up-regulate the expression of the seladin-1 gene in in vitro models of human neuronal precursors.
abstract: 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.
authors.affiliation: 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', University of Florence, Florence, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Benvenuti
authors.forename: P
authors.initials: P
authors.lastname: Luciani
authors.forename: I
authors.initials: I
authors.lastname: Cellai
authors.forename: C
authors.initials: C
authors.lastname: Deledda
authors.forename: S
authors.initials: S
authors.lastname: Baglioni
authors.forename: R
authors.initials: R
authors.lastname: Saccardi
authors.forename: S
authors.initials: S
authors.lastname: Urbani
authors.forename: F
authors.initials: F
authors.lastname: Francini
authors.forename: R
authors.initials: R
authors.lastname: Squecco
authors.forename: C
authors.initials: C
authors.lastname: Giuliani
authors.forename: G B
authors.initials: GB
authors.lastname: Vannelli
authors.forename: M
authors.initials: M
authors.lastname: Serio
authors.forename: A
authors.initials: A
authors.lastname: Pinchera
authors.forename: A
authors.initials: A
authors.lastname: Peri
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D011988:Receptors, Thyroid Hormone / Q000235:genetics; D012964:Sodium / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D020746:Calcium Channels, L-Type; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D012964:Sodium; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human; D002118:Calcium