RESUMO
A scheme of complex administration of drugs in the order neuroprotector + neuroactivator + neuroretarder for the treatment of neurodegenerative processes in the brain has been elaborated and tested on a model object representing neurodegenerative mutants of Drosophila melanogaster. The appearance of changes in the brain was delayed when drugs were used separately: donepezil hydrochloride (arisept), 10 - 11 days, epinephrine and nimodipine, 1 - 2 days. The treatment of flies with the same drugs in the order arisept + epinephrine + nimodipine leads to the complete regeneration of D. melanogaster brain tissue to within 15 days of imago life.
Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Epinefrina/uso terapêutico , Indanos/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Nimodipina/uso terapêutico , Nootrópicos/uso terapêutico , Piperidinas/uso terapêutico , Animais , Modelos Animais de Doenças , Donepezila , Drosophila melanogaster , Quimioterapia Combinada , Mutação , Doenças Neurodegenerativas/genéticaRESUMO
Under the influence of ethyl methanesulfonate the series of both morphological and structural mutants with different types of brain changes has been obtained in Drosophila melanogaster Oregon R strain. In the future, this collection of mutants will be used in the investigations of genetic control of brain degeneration and possible ways of brain regeneration.
Assuntos
Encéfalo/citologia , Drosophila melanogaster/efeitos dos fármacos , Metanossulfonato de Etila/farmacologia , Mutagênicos/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Drosophila melanogaster/citologia , Drosophila melanogaster/genética , Feminino , Masculino , Mutação , Cromossomo X/efeitos dos fármacosRESUMO
The genetic instability of Drosophila melanogaster genes induced by the mobile genetic elements is reviewed. The main attention is paid to genetic instability depended on types of crossing. Data on the possibility of genetic instability induction by the chemical and physical (X-rays, heat-shock) agents and their complex effect are cited. It was shown that a number of agents which cause mutagenic effect realize their action by involving of mobile genetic elements.
Assuntos
Drosophila melanogaster/genética , Genes de Insetos/genética , Variação Genética/genética , Sequências Repetitivas Dispersas/genética , Animais , Troca Genética/efeitos dos fármacos , Troca Genética/genética , Troca Genética/efeitos da radiação , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/efeitos da radiação , Genes de Insetos/efeitos dos fármacos , Genes de Insetos/efeitos da radiação , Variação Genética/efeitos dos fármacos , Variação Genética/efeitos da radiação , Sequências Repetitivas Dispersas/efeitos dos fármacos , Sequências Repetitivas Dispersas/efeitos da radiaçãoRESUMO
A novel system of prolonged genetic instability induced by N-ethyl-N-nitrosourea in D. melanogaster was obtained. The instability was associated with the appearance of new mutations in loci yellow, scute, white, cut, singed, miniature, vermilion and extended for 40 generations. Some mutants of locus cut were obtained by the method of Southern blot-hybridisation. The reversion ct+ appeared as a result of excision of gypsy element. The mutation ctpN34 was localized in the second complementation group of cut locus and was the consequent of deletions of gypsy element and small DNA fragment and an insertion of a DNA sequence 7.8 kb in size.
Assuntos
Etilnitrosoureia/farmacologia , Variação Genética/efeitos dos fármacos , Mutagênicos/farmacologia , Animais , DNA/genética , Drosophila melanogaster , Feminino , Variação Genética/genética , Genótipo , Larva , Masculino , Mutação , LinhagemRESUMO
Molecular genetic mechanisms of the white mutations induced by mitomycin C, N-ethyl-N-nitrosourea, and ethidium bromide were studied. Genomic DNA of the original strain and mutants obtained was tested by Southern blot hybridization. The presence of mobile genetic elements was shown to be characteristic of the white locus of the original strain. Mutations of the white gene obtained mainly resulted from excision of DNA sequences involving mobile genetic elements and insertion of unidentified 5-6-kbp DNA fragments.
Assuntos
Mapeamento Cromossômico , Drosophila melanogaster/efeitos dos fármacos , Mitomicina/toxicidade , Mutagênese Insercional , Mutagênicos/toxicidade , Animais , Southern Blotting , Elementos de DNA Transponíveis , Drosophila melanogaster/genética , Etídio/toxicidade , Etilnitrosoureia/toxicidade , GenomaRESUMO
The influence of mitomycin C on the genetic stability of Drosophila laboratory lines was investigated. This mutagen caused one-locus and multi-loci mutations with high frequencies (approximately 10(-2), 10(-3)) in the first and the second generations. It is locus-specific mutagenesis. In situ hybridization experiments indicated the existence of primary and new sites of location of mobile genetic elements mdg 1, mdg 2, mdg 4. This instability was caused by activation of transposition and recombination.
Assuntos
Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Mitomicina/farmacologia , Mutação , Animais , DNA/genética , Elementos de DNA Transponíveis/efeitos dos fármacos , Elementos de DNA Transponíveis/genética , Feminino , Genótipo , Hibridização In Situ , Masculino , Cromossomo X/efeitos dos fármacos , Cromossomo X/genéticaRESUMO
The phenomenon of transpositional bursts-massive simultaneous transpositions of mobile elements belonging to different structural classes and accompanied by multiple mutagenesis were earlier described. Although the mechanisms of this phenomenon are still unclear, it is obvious now that it embraces total genome and includes not only transpositions of different mobile elements but also recombination processes--homologous recombination for LTR's and gene conversion. It is shown in this work that transpositional bursts may be accompanied by appearance of grass chromosomal rearrangements. The chain of closely related mutations which is characterized, as well as pedigrees described earlier, by coordinated mutational transitions and multiple transpositions of mdg1, mdg2 and retrotransposon jokey was analyzed. Spontaneous appearance of mutations in the loci yellow, white (deficiency for 462 kb) and cut (insertion of mdg4, together with jokey) correlates with appearance of inversion In(I), 14A-20B, and the reversions of these mutations to the wild type (y+w+ct+) or to other alleles (ctMR2--insertion of mdg4 without jokey) are accompanied by reversions of inversion. The relationship of all lines analyzed in this work as well as the lines from other pedigrees was proved using analysis of polymorphic restriction sites at the scute and cut loci (5 probes were used). All "y w ctpN"--type mutants are shown to have insertion of about 7 kb at the scute locus which causes no alteration of phenotype. This once again proves multiple and coordinated character of changes taking place during hybrid dysgenesis.
Assuntos
Elementos de DNA Transponíveis , Drosophila melanogaster/genética , Animais , DNA/genética , Cariotipagem , Mutação , Hibridização de Ácido Nucleico , Polimorfismo de Fragmento de Restrição , Mapeamento por RestriçãoRESUMO
The ontogenesis of Drosophila melanogaster displays changes in the activity of LDH and a redistribution of the enzyme electrophoretic fractions. The results obtained show that the changes in the electrophoretic spectrum of LDH occur at the level of isoenzymes and multiple molecular forms, which is in full accord with the assumption on the existence of two genes of LDH and suggests their regulation at both the gene level and posttranslation modifications.