Caracterización De Nuevos Modelos Animales Para El Estudio De La Enfermedad De Alzheimer
Caracterización de nuevos modelos animales para el estudio de la enfermedad de alzheimer
| dc.contributor | Inestrosa Cantín, Nibaldo | |
| dc.contributor | PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE | |
| dc.creator | Reyes Zambrano, Ariel Eduardo | |
| dc.date | 2019-01-02T20:28:57Z | |
| dc.date | 2022-08-23T12:52:10Z | |
| dc.date | 2019-01-02T20:28:57Z | |
| dc.date | 2022-08-23T12:52:10Z | |
| dc.date | 2000 | |
| dc.date.accessioned | 2023-08-22T00:08:40Z | |
| dc.date.available | 2023-08-22T00:08:40Z | |
| dc.identifier | 195109 | |
| dc.identifier | https://hdl.handle.net/10533/232843 | |
| dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/8299085 | |
| dc.description | Alzheimer's Disease (AD) is histopathologically characterized by the presence, within the brain, of lesions called senile plaques (SP) and neurofibrillary tangles (NFT). SP are fibrillar deposits mainly composed by beta-amyloid peptide. SP onset is an early event in AD pathogenesis, and for that reason its genesis is of particular interest for the study of the disease. Previous studies in our lab have demonstrated that the enzyme acetylcholinesterase (AChE), that colocalizes within SP, is able to promote, in vitro, fibrillary aggregates of A-beta peptide, increasing its neurotoxicity. In consequence, we decided to evaluate its in vivo effect on the generation of these aggregates. Such a study is complicated by the fact that wild type classic rodents (rats and mice) do not constitute accurate animal models for AD study. This is because the existence of lesions analogous to those found within AD affected human brains has not been documented in them. In view of this, rats were intracerebrally injected with A-beta peptide fibrils assembled in vitro in the presence and absence of AChE. The presence of AChE injected fibrils induces rat endogenous A-beta peptide aggregation, and recruitment of endogenous laminin, generating a lesion resembling a SP. In addition, the injection of AChE-A-beta complexes results in a local neurodegeneration augmented with respect to what is observed when A-beta fibrils are injected. This treatment induces a cognitive impairment detectable by the Morris water maze. To study the effect of an acute local increase of AChE within rat hippocampus, the enzime was injected and the response evaluated from histological and conductual points of view. This treatment induces neuronal loss in a region adjacent to the injection site, correlating with spatial memory impairment. Continuous infusion of AChE within rat hippocampus promotes endogenous A-beta peptide aggregation, in the form of amyloid-like aggregates similar to SP, that are able to recruit endogenous proteins that colocalize with human SP, such as laminin and perlecan. Under these circumstances, we report an increase on the immunodetection of the enzyme glycogen synthase kinase-3beta, responsible for tau-protein hyperphosphorylation, which is the main component of NFT. Evidence is presented indicating that, in response to a known excitotoxic injury, as is ibotenic acid injection, there is an increase in AChE catalytic activity and expression within rat hippocampus. Finally, we characterized an alternative rodent model for AD study (Octodon degu), which exhibits, in native conditions, intra- and extra-cellular amyloid aggregates, as well as tau-protein intracellular aggregates, observations that resemble SP and NFT in early stages of AD. Possible causes of this species-specific observation are discussed. | |
| dc.description | PFCHA-Becas | |
| dc.description | PFCHA-Becas | |
| dc.format | application/pdf | |
| dc.relation | instname: Conicyt | |
| dc.relation | reponame: Repositorio Digital RI2.0 | |
| dc.relation | info:eu-repo/grantAgreement//195109 | |
| dc.relation | info:eu-repo/semantics/dataset/hdl.handle.net/10533/93488 | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.rights | http://creativecommons.org/publicdomain/zero/1.0/ | |
| dc.subject | Ciencias Naturales | |
| dc.subject | Medicina Básica | |
| dc.subject | Biología Celular | |
| dc.title | Caracterización De Nuevos Modelos Animales Para El Estudio De La Enfermedad De Alzheimer | |
| dc.title | Caracterización de nuevos modelos animales para el estudio de la enfermedad de alzheimer | |
| dc.type | Tesis Doctorado | |
| dc.type | info:eu-repo/semantics/doctoralThesis | |
| dc.type | info:eu-repo/semantics/publishedVersion | |
| dc.type | Tesis |