title: Effect of thyroid hormone T3 on myosin-Va expression in the central nervous system.
abstract: Thyroid hormones (THs) are essential for brain development, where they regulate gliogenesis, myelination, cell proliferation and protein synthesis. Hypothyroidism severely affects neuronal growth and establishment of synaptic connections. Triiodothyronine (T3), the biologically active form of TH, has a central function in these activities. So, Myosin-Va (Myo-Va), a molecular motor protein involved in vesicle and RNA transport, is a good candidate as a target for T3 regulation. Here, we analyzed Myo-Va expression in euthyroid and hypothyroid adult rat brains and synaptosomes. We observed a reduction of Myo-Va expression in cultured neural cells from newborn hypothyroid rat brain, while immunocytochemical experiments showed a punctate distribution of this protein in the cytoplasm of cells. Particularly, Myo-Va co-localized with microtubules in neurites, especially in their varicosities. Myo-Va immunostaining was stronger in astrocytes and neurons of controls when compared with hypothyroid brains. In addition, supplementation of astrocyte cultures with T3 led to increased expression of Myo-Va in cells from both euthyroid and hypothyroid animals, suggesting that T3 modulates Myo-Va expression in neural cells both in vivo and in vitro. We have further analyzed Myo-Va expression in U373 cells, a human glioblastoma line, and found the same punctate cytoplasmic protein localization. As in normal neural cells, this expression was also increased by T3, suggesting that the modulatory mechanism exerted by T3 over Myo-Va remains active on astrocyte tumor cells. These data, coupled with the observation that Myo-Va is severely affected in hypothyroidism, support the hypothesis that T3 activity regulates neural motor protein expression, taking Myo-Va as a model. As a consequence, reduced T3 activity could supposedly affect axonal transport and synaptic function, and could therefore explain disturbances seen in the hypothyroid brain.
authors.affiliation: Programa de Anatomia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, CEP 21941-590, Rio de Janeiro, Brazil.
authors.forename: Sheila Cristina
authors.initials: SC
authors.lastname: de Souza Martins
authors.forename: Luciana Ferreira
authors.initials: LF
authors.lastname: Romão
authors.forename: Jane Cristina
authors.initials: JC
authors.lastname: Faria
authors.forename: Rosenilde Carvalho
authors.initials: RC
authors.lastname: de Holanda Afonso
authors.forename: Samantha Angel
authors.initials: SA
authors.lastname: Murray
authors.forename: Claudia Helena
authors.initials: CH
authors.lastname: Pellizzon
authors.forename: John A
authors.initials: JA
authors.lastname: Mercer
authors.forename: Luiz-Claudio
authors.initials: LC
authors.lastname: Cameron
authors.forename: Vivaldo
authors.initials: V
authors.lastname: Moura-Neto
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018995:Myosin Heavy Chains / Q000096:biosynthesis*; D024701:Myosin Type V / Q000096:biosynthesis*; D011247:Pregnancy; D051381:Rats; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D014284:Triiodothyronine; C077511:MYO5A protein, human; D024701:Myosin Type V; D018995:Myosin Heavy Chains