Publicação
Analysis of the expression of taste and olfactory receptors in choroid plexus and orbitofrontal cortex of Alzheimer’s disease patients
| Resumo: | Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by progressive memory loss and cognitive deterioration, attributed to neuropathological lesions within specific regions in the brain. However, other areas of the brain such as the choroid plexus and the orbitofrontal cortex, have gained much attention since the choroid plexus is a multifunctional tissue responsible for a wide range of functions crucial to the central nervous system and the orbitofrontal cortex is considered among the most polymodal regions of the brain. Previous studies have shown the expression of taste and olfactory transduction pathways in rat choroid plexus as well as taste and olfactory regulation and activation of orbitofrontal cortex. Therefore the present work aimed to study the expression of taste and olfactory receptors in the choroid plexus and orbitofrontal cortex of AD patients. Towards this aim, transcriptomic analysis of these chemoreceptors were performed by means of Real-time quantitative Polymerase Chain Reaction (RT-qPCR), and compared between AD patients (at different Braak stages of the disease) and age-matched controls. Transcriptomic analysis indicated that orbitofrontal cortical olfactory receptors (ORs) and taste receptors (TASRs) are expressed and regulated at different stages of AD in female patients, whereas in male this regulation was not observed. Moreover, olfactory receptors OR2K2, OR2H2, and OR1L8 and taste receptor TAS2R14 were downregulated at Braak stages I, V, VI, compared to age-matched controls in the orbitofrontal cortex of female AD patients. The strongest differences were found at Braak stage I of AD, suggesting that dysregulation of ORs and TASRs is an early event in the pathogenesis of AD in female patients. Also, that ORs and TASRs in the orbitofrontal cortex might be differently affected in male and female AD patients. These receptors we also found to be expressed in choroid plexus, however, due to their low expression we were not able to quantify the relative mRNA levels by RT-qPCR. Nevertheless further studies are needed in order to strengthen these findings and to elucidate their potential physiologic functions in this brain area. |
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| Autores principais: | Alves, Victória da Cunha |
| Assunto: | Alzheimer´S Disease Choroid Plexus Olfactory Receptors Orbitofrontal Cortex Real Time Quantitative Pcr Taste Receptors |
| Ano: | 2016 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade da Beira Interior |
| Idioma: | inglês |
| Origem: | uBibliorum |
| Resumo: | Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by progressive memory loss and cognitive deterioration, attributed to neuropathological lesions within specific regions in the brain. However, other areas of the brain such as the choroid plexus and the orbitofrontal cortex, have gained much attention since the choroid plexus is a multifunctional tissue responsible for a wide range of functions crucial to the central nervous system and the orbitofrontal cortex is considered among the most polymodal regions of the brain. Previous studies have shown the expression of taste and olfactory transduction pathways in rat choroid plexus as well as taste and olfactory regulation and activation of orbitofrontal cortex. Therefore the present work aimed to study the expression of taste and olfactory receptors in the choroid plexus and orbitofrontal cortex of AD patients. Towards this aim, transcriptomic analysis of these chemoreceptors were performed by means of Real-time quantitative Polymerase Chain Reaction (RT-qPCR), and compared between AD patients (at different Braak stages of the disease) and age-matched controls. Transcriptomic analysis indicated that orbitofrontal cortical olfactory receptors (ORs) and taste receptors (TASRs) are expressed and regulated at different stages of AD in female patients, whereas in male this regulation was not observed. Moreover, olfactory receptors OR2K2, OR2H2, and OR1L8 and taste receptor TAS2R14 were downregulated at Braak stages I, V, VI, compared to age-matched controls in the orbitofrontal cortex of female AD patients. The strongest differences were found at Braak stage I of AD, suggesting that dysregulation of ORs and TASRs is an early event in the pathogenesis of AD in female patients. Also, that ORs and TASRs in the orbitofrontal cortex might be differently affected in male and female AD patients. These receptors we also found to be expressed in choroid plexus, however, due to their low expression we were not able to quantify the relative mRNA levels by RT-qPCR. Nevertheless further studies are needed in order to strengthen these findings and to elucidate their potential physiologic functions in this brain area. |
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