Publicação
Vascular and glial alterations during aging in wild-type mice and along Alzheimer's disease progression in APP/PS1 mice
| Resumo: | The blood-brain barrier (BBB) is more than a loyal protecting wall of the central nervous system (CNS). The BBB is a dynamic bidirectional interface between the CNS and blood, formed by endothelial cells, basement membrane, pericytes and astrocytes endfeet. Since its unique properties and location, it is a central player in the maintenance of CNS microenvironment. The communication between the BBB and the neurovascular unit components, microglia and neurons, was found to be crucial for the CNS homeostasis, as it was found to be dysfunctional in aged brain and in Alzheimer’s disease (AD) patients brain. Based on this, we aimed to investigate which vascular and glial events are characteristic of AD or/and aging, as well as to establish the temporal evolution of these changes in AD-like APP/PS1 and wild-type (WT) mice. Moreover, we aimed to relate these changes with amyloid-β (Aβ) accumulation. We used hippocampi and cortex to analyze the temporal evolution of selected parameters in a young adult, a middle age and an old age group. Our results show that aging is the main factor contributing to the upregulation of receptor for advanced glycation endproducts and desmin, as well as to the entrance of thrombin and albumin in hippocampus parenchyma. On the other hand, AD was found to be the unique contributing factor to the loss of platelet-derived growth factor receptor-β (PDGFR-β) positive cells, in both studied regions. Both factors contributed to hypovascularization in hippocampus, but in cortex it was just a reflex of the interaction between both factors. Astrogliosis was a result of AD in hippocampus and it is a reflex of both factors in cortex, while microgliosis is a result of AD and the interaction between both factors in both regions. Regarding the relationship between glia-vascular changes and senile plaques, we found that senile plaques precede vascular and glial alterations in hippocampus. Interestingly, in cortex, vascular and glial alterations, specifically loss of PDGFR-β-positive cells and astrogliosis, accompanied the first senile plaques. In sum, this study points to vascular and glial events that can underline AD pathogenesis and age-related brain vulnerabilities. |
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| Autores principais: | Janota, Cátia Alexandra da Silva |
| Assunto: | Endothelial cells Pericytes Blood-brain barrier disruption Glial activation Alzheimer’s disease Aging Teses de mestrado - 2014 |
| Ano: | 2014 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | The blood-brain barrier (BBB) is more than a loyal protecting wall of the central nervous system (CNS). The BBB is a dynamic bidirectional interface between the CNS and blood, formed by endothelial cells, basement membrane, pericytes and astrocytes endfeet. Since its unique properties and location, it is a central player in the maintenance of CNS microenvironment. The communication between the BBB and the neurovascular unit components, microglia and neurons, was found to be crucial for the CNS homeostasis, as it was found to be dysfunctional in aged brain and in Alzheimer’s disease (AD) patients brain. Based on this, we aimed to investigate which vascular and glial events are characteristic of AD or/and aging, as well as to establish the temporal evolution of these changes in AD-like APP/PS1 and wild-type (WT) mice. Moreover, we aimed to relate these changes with amyloid-β (Aβ) accumulation. We used hippocampi and cortex to analyze the temporal evolution of selected parameters in a young adult, a middle age and an old age group. Our results show that aging is the main factor contributing to the upregulation of receptor for advanced glycation endproducts and desmin, as well as to the entrance of thrombin and albumin in hippocampus parenchyma. On the other hand, AD was found to be the unique contributing factor to the loss of platelet-derived growth factor receptor-β (PDGFR-β) positive cells, in both studied regions. Both factors contributed to hypovascularization in hippocampus, but in cortex it was just a reflex of the interaction between both factors. Astrogliosis was a result of AD in hippocampus and it is a reflex of both factors in cortex, while microgliosis is a result of AD and the interaction between both factors in both regions. Regarding the relationship between glia-vascular changes and senile plaques, we found that senile plaques precede vascular and glial alterations in hippocampus. Interestingly, in cortex, vascular and glial alterations, specifically loss of PDGFR-β-positive cells and astrogliosis, accompanied the first senile plaques. In sum, this study points to vascular and glial events that can underline AD pathogenesis and age-related brain vulnerabilities. |
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