If the importance of triiodothyronine (T3) on brain development including myelinogenesis has long been recognized, its mechanism of action at the gene level is still not fully elucidated. We studied the effect of T3 on the expression of myelin protein genes in aggregating brain cell cultures. T3 increases the concentrations of mRNA transcribed from the following four myelin protein genes: myelin basic protein (Mbp), myelin-associated glycoprotein (Mag), proteolipid protein (Plp), and 2',3'-cyclic nucleotide 3'-phosphodiesterase (Cnp). T3 is not only a triggering signal for oligodendrocyte differentiation, but it has continuous stimulatory effects on myelin gene expression. Transcription in isolated nuclei experiments shows that T3 increases Mag and Cnp transcription rates. After inhibiting transcription with actinomycin D, we measured the half-lives of specific mRNAs. Our results show that T3 increases the stability of mRNA for myelin basic protein, and probably proteolipid protein. In vitro translation followed by myelin basic protein-specific immunoprecipitation showed a direct stimulatory effect of T3 on myelin basic protein mRNA translation. Moreover, this stimulation was higher when the mRNA was already stabilized in culture, indicating that stabilization is achieved through mRNA structural modifications. These results demonstrate the diverse and multiple mechanisms of T3 stimulation of myelin protein genes.
Penetration of the central nervous system of the adult rat by the CVS strain of rabies virus and its two avirulent derivatives AvOl and AvO2 has been studied by inoculation of the virus into the anterior chamber of the eye. The primary sites of penetration of CVS were (i) the intraocular parasympathetic oculomotor fibers, (ii) the retinopetal fibers of pretectal origin, and (iii) the intraocular fibers of the ophthalmic nerve. The mutant strains, however, lost the capacity to invade the two former groups of fibers, although their penetration into the trigeminal system was not impaired. Neither strain CVS nor the mutants infected primarily the intraocular adrenergic terminals and the optic nerve. Mutant strains, but not CVS, were able to infect the lens. These results indicate that the cholinergic receptor may not be the only receptor for rabies virus and that rabies virus is conveyed in the nervous system by retrograde axoplasmic flow. Strain CVS spread throughout the brain and propagated eventually back to the retina. The mutants penetrated the brain as well, but the infection was slow, involved different cerebral structures, and cleared up completely in 3 weeks, probably because of an efficient immune response.
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