| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 2.33 MB | Adobe PDF |
Authors
Advisor(s)
Abstract(s)
O plexo coróide (PC) tem um papel fundamental na remoção do péptido beta-amilóide (Ab),
que é um dos principais factores causadores da doença de Alzheimer (DA), do líquido
cefalorraquidiano (LCR), evitando a sua acumulação e consequente morte neuronal. Na DA, o
PC desenvolve disfunções semelhantes às observadas durante a senescência, nomeadamente a
atrofia acentuada do seu epitélio, alterando significativamente as suas funcionalidades,
culminando com a elevação da concentração de Ab no cérebro. Todas as estratégias de
tratamento da DA têm sido direcionadas para o tratamento de sintomas e não para a sua
prevenção. Por isso, é cada vez mais importante desenvolver estratégias terapêuticas
preventivas no aparecimento desta patologia neurodegenerativa.
O PC é um alvo reconhecido das hormonas sexuais, e estes esteróides afectam a expressão de
genes responsáveis pela eliminação de Ab, podendo ser determinantes na progressão da DA. O
objectivo deste trabalho foi analisar a expressão de genes dos scavengers de Ab no PC de
ratos Wistar Han recém-nascidos e estudar o efeito do tratamento com estradiol (E2) na
expressão destes genes e, portanto, na DA. Principiou-se pela análise de vários genes dos
scavengers de Ab (TTR, MT-2, IDE, GSN e ApoJ), por PCR convencional, em explantes de PC de
ratos Wistar Han recém-nascidos, confirmando-se a sua expressão neste epitélio.
Ulteriormente, a expressão dos genes dos scavengers de Ab, sob tratamento de E2 em
concentrações crescentes (10 nm e 100 nm) foi comparada por PCR em tempo real,
verificando-se que estes genes são diferentemente expressos entre o grupo tratado com E2 e o
grupo de controlo. Por meio desta análise, podemos concluir que os estrogénios influenciam a
expressão de algumas proteínas responsáveis pela depleção de Ab, podendo a terapia
hormonal (TH) ter uma carácter preventivo contra a DA.
The choroid plexus (CP) has a key role on the clearance of amyloid-beta peptide (Ab) from the cerebrospinal fluid (CSF), which is one of the major causative factors of Alzheimer’s disease (AD), there by preventing its accumulation and consequent neuronal death. In this disease, CP develops dysfunctions similar to those seen during aging, including a significantly marked atrophy of the epithelium. Such modifications may alter the CP functions and hence, might increase the concentration of the O-amyloid (AO) peptide in the brain. All treatment strategies of AD have been targeted for the treatment of symptoms and not for its prevention. Therefore, it is increasingly important to develop preventive therapeutic strategies in the onset of this neurodegenerative disease. CP is a recognized target for sex hormones, and these sex hormones affect the expression of several genes responsable for the clearance of Ab and thus may affect the progression o AD. The aim of this work was to analyze the expression of scavenging genes of Ab in rat CP and study the effect of estradiol (E2) treatment in the expression of these genes, which may have an important role in neuroprotection against Ab and hence Alzheimer's disease. We began by analyzing the expression of several genes with Ab-scavenging properties (TTR, MT-2, IDE, GSN and ApoJ), by PCR, in the CP explants of newborn Wistar Han rats, confirming their expression in this epithelia. Later, the expression of TTR, MT-2, IDE, GSN and ApoJ, under treatment E2 (in two concentrations: 10 nm and 100 nm), was compared by Real-time PCR through which it was possible to confirm that these genes are differentially expressed between treated and non-treated rats. From this analysis we conclude that estrogens can influence the expression of some proteins associated with the clearance of Ab, and extrapolate that hormone therapy might have a preventive character against AD.
The choroid plexus (CP) has a key role on the clearance of amyloid-beta peptide (Ab) from the cerebrospinal fluid (CSF), which is one of the major causative factors of Alzheimer’s disease (AD), there by preventing its accumulation and consequent neuronal death. In this disease, CP develops dysfunctions similar to those seen during aging, including a significantly marked atrophy of the epithelium. Such modifications may alter the CP functions and hence, might increase the concentration of the O-amyloid (AO) peptide in the brain. All treatment strategies of AD have been targeted for the treatment of symptoms and not for its prevention. Therefore, it is increasingly important to develop preventive therapeutic strategies in the onset of this neurodegenerative disease. CP is a recognized target for sex hormones, and these sex hormones affect the expression of several genes responsable for the clearance of Ab and thus may affect the progression o AD. The aim of this work was to analyze the expression of scavenging genes of Ab in rat CP and study the effect of estradiol (E2) treatment in the expression of these genes, which may have an important role in neuroprotection against Ab and hence Alzheimer's disease. We began by analyzing the expression of several genes with Ab-scavenging properties (TTR, MT-2, IDE, GSN and ApoJ), by PCR, in the CP explants of newborn Wistar Han rats, confirming their expression in this epithelia. Later, the expression of TTR, MT-2, IDE, GSN and ApoJ, under treatment E2 (in two concentrations: 10 nm and 100 nm), was compared by Real-time PCR through which it was possible to confirm that these genes are differentially expressed between treated and non-treated rats. From this analysis we conclude that estrogens can influence the expression of some proteins associated with the clearance of Ab, and extrapolate that hormone therapy might have a preventive character against AD.
Description
Keywords
Beta-Amilóide Doença de Alzheimer Estrogénios Plexo Coróide Scavenger