RESUMO
Thyroid hormones are critical for maturation of the central nervous system. In a previous study, we showed a change in the pattern of mature myelinated nerve fibers by 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in developing hypothyroid animals, which suggests a possible role for thyroid hormones in myelin compaction. The classical myelin markers myelin basic protein (MBP) and proteolipidic protein (PLP) are expressed later in oligodendroglial development, when myelin sheath formation is in progress. A myelin constituent designated myelin-associated/oligodendrocytic basic protein (MOBP) has been identified and related to myelin compaction. We assessed the developmental sequence of appearance of CNPase, MBP, MOPB, and PLP proteins in cerebellum (Cb) and corpus callosum (cc) in an experimental hypothyroidism model. The appearance of both MOBP isoforms occurred at postnatal day (P)25 and P30 in cc and Cb, respectively, followed by an increase with age in the control group. However, all the MOBP isoforms were weakly detectable in both regions at P30 from the hypothyroid (H) group, and the higher molecular weight isoform remains decreased in cc, even at P90. The developmental pattern of expression of CNPase, MBP, and PLP proteins was also delayed in the H group. CNPase and MBP expression was recovered in cc and Cb, whereas PLP remained below control levels at P90 in cc. Our data show that the experimental hypothyroidism affects the developmental pattern of the oligodendrocytic/myelin markers. Furthermore, thyroid hormone may modulate specific genes, as demonstrated by permanent down-regulation of MOBP and PLP expression in adulthood.
Assuntos
2',3'-Nucleotídeo Cíclico Fosfodiesterases/biossíntese , Doenças Fetais/metabolismo , Proteínas Fetais/biossíntese , Regulação da Expressão Gênica no Desenvolvimento , Hipotireoidismo/metabolismo , Proteína Básica da Mielina/biossíntese , Proteína Proteolipídica de Mielina/biossíntese , Glicoproteína Associada a Mielina/biossíntese , 2',3'-Nucleotídeo Cíclico Fosfodiesterases/genética , Animais , Cerebelo/embriologia , Cerebelo/crescimento & desenvolvimento , Cerebelo/metabolismo , Hipotireoidismo Congênito , Corpo Caloso/crescimento & desenvolvimento , Corpo Caloso/metabolismo , Feminino , Doenças Fetais/genética , Proteínas Fetais/genética , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/embriologia , Hipotireoidismo/genética , Metimazol/toxicidade , Proteína Básica da Mielina/genética , Proteínas da Mielina , Proteína Proteolipídica de Mielina/genética , Glicoproteína Associada a Mielina/genética , Glicoproteína Mielina-Oligodendrócito , Gravidez , Complicações na Gravidez , Isoformas de Proteínas/biossíntese , Isoformas de Proteínas/genética , Ratos , Ratos WistarRESUMO
Transferrin (Tf) is a possible regulator of oligodendrocyte development in vitro (Espinosa de los Monteros et al., 1989). At least two different mechanisms may account for the effects of Tf on myelin synthesis. It may act as a trophic factor and enhance the formation of new myelin sheaths. Tf may also induce the synthesis of myelin proteins in the central nervous system. We recently demonstrated that a single intracranial injection of apotransferrin (aTf) in young rats induces an increased myelination (Escobar Cabrera et al., 1994). In the present study, we investigated the in vivo effect of aTf on the expression of mRNAs of specific myelin genes. Three-day-old rats were injected intracranially with aTf and killed at different ages after injection. Total brain RNA was isolated, and the expression of different mRNAs was analyzed by Northern blot. The amount of mRNAs of myelin basic protein and of 2'-3' cyclic nucleotide 3'-phosphohydrolase were markedly increased in the experimental animals, whereas myelin proteolipid protein mRNA did not show differences relative to controls. These results indicate that in the animals treated with aTf, there is a differential effect on the expression of certain specific myelin protein genes. They also suggest that aTf might exert its action at the posttranscriptional level and/or by direct transcriptional regulation of the genes.