title: Thyroid hormone promotes BCL-2 expression and prevents apoptosis of early differentiating cerebellar granule neurons.
abstract: Programmed cell death is a basic cellular process that has aroused much interest in recent years. Like immune cells, cultures of cerebellar granule neurons are very homogeneous and provide a unique opportunity for quantifying by flow cytometry one form of programmed cell death in the CNS, the apoptosis, and for studying its regulation by neurotrophic factors. We found that thyroid hormone promoted postmitotic survival by preventing the apoptosis of newly formed and early differentiated granule neurons in a dose-dependent manner. This regulation could be through the protein bcl-2, which is known to prevent cell death. This protein was present at all stages of granule neuron differentiation and appeared to be developmentally regulated. It was underexpressed in apoptotic granule neurons. The protein content of the cerebellum in hypothyroid rats was drastically reduced. In contrast, thyroid hormone caused a marked dose-dependent increase in the amounts of this protein in granule neuron cultures. The possibility that thyroid hormone may be directly or indirectly required to promote cell survival is discussed, in terms of the hormone control of the local delivery of neurotrophins, such as NGF and NT-3, as well as the expression of their low affinity receptors, gp75. We suggest that thyroid hormone has a permissive action on the developing CNS.
authors.affiliation: Laboratoire de Neurobiologie Endocrinologique, URA 1197 CNRS, Université Montpellier II, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Muller
authors.forename: E
authors.initials: E
authors.lastname: Rocchi
authors.forename: J B
authors.initials: JB
authors.lastname: Lazaro
authors.forename: J
authors.initials: J
authors.lastname: Clos
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development*; D004247:DNA / Q000378:metabolism; D005434:Flow Cytometry; D019085:Fluorescent Antibody Technique, Direct; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism; D007150:Immunohistochemistry; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D011441:Propylthiouracil; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000494:pharmacology*
chemical_list: D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013963:Thyroid Hormones; D011441:Propylthiouracil; D004247:DNA; D011505:Protein-Tyrosine Kinases