Estudio de alteraciones asociadas al ritmo circadiano en modelo animal de Alzheimer: ratones APP/PS1

Rodríguez Jiménez, María (2019). Estudio de alteraciones asociadas al ritmo circadiano en modelo animal de Alzheimer: ratones APP/PS1. Proyecto Fin de Carrera / Trabajo Fin de Grado, E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM), Madrid.

Description

Title: Estudio de alteraciones asociadas al ritmo circadiano en modelo animal de Alzheimer: ratones APP/PS1
Author/s:
  • Rodríguez Jiménez, María
Contributor/s:
  • Carro Díaz, Eva María
  • Ramírez Castillejo, María del Carmen
Item Type: Final Project
Degree: Grado en Biotecnología
Date: June 2019
Subjects:
Faculty: E.T.S. de Ingeniería Agronómica, Alimentaria y de Biosistemas (UPM)
Department: Biotecnología - Biología Vegetal
Creative Commons Licenses: Recognition - No derivative works - Non commercial

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Abstract

Alzheimer’s disease is a degenerative brain disease and the most common cause of dementia. This disease affects 36 million people worldwide each year. Alzheimer’s disease is considered by the World Health Organization as a public health priority. Microscopically, this pathology is characterized by two typical brain lesions: neuritic plaques and neuronal tangles. The neuritic plaques are extracellular, caused by amyloid-β (Aβ) peptide accumulation. However, the neuronal tangles are intracellular, principally at neuronal level, caused by hyperphosphorylated Tau protein accumulation. Alzheimer’s disease is classified in two types: sporadic and familiar. Although clinical phenotype is similar, each type presents different etiology. Familiar Alzheimer’s disease is caused by mutations in three genes: APP which encodes amyloid precursor protein, PSEN1 encoding presenilin 1 and PSEN2 encoding presenilin 2. Sleep disruptions and disturbances in the wake-sleep cycle are common symptoms of Alzheimer’s disease, and one of the main causes of mortality and morbidity. It is believed that these symptoms appear at moderate level of the disease. The wake-sleep cycle is controlled by the circadian clock that is present in our body. The human circadian clock is a hierarchy of oscillators with the suprachiasmatic nucleus (SCN) of the anterior hypothalamus at the top of this hierarchy. Circadian clock is not only present in the SCN, but also it is present in brain tissues extra-SCN and in the majority of our peripheral tissues. Circadian clock is principally composed by the genes CLOCK, ARNTL, PER1, PER2, PER3, CRY1 and CRY2. Disturbances in the circadian clock system are common in Alzheimer’s disease patients and are related to the wake-sleep cycle, the diary activities and the body thermoregulation. These disturbances are presented as an aggravated form of the common ones of elder people due to the aging. The main objective of this work has been to analyze the levels of two protein encoded by two main circadian system genes, CLOCK and BMAL1. This study was developed at the level of hippocampus, implicated in the memory formation, and cerebral cortex, implicated in sleep control, in an advanced stage of the disease as these areas are the most affected brain areas in Alzheimer’s disease. Therefore, we ix have used an animal model of familiar Alzheimer disease, APP/PS1 mice at the age of 12 months, mimicking an advanced stage of the pathology. Depending on the brain region, we could observe differences in protein levels comparing APP/PS1 mice with WT animals. Our results point to alterations in circadian rhythm in APP/PS1 compared to WT animal.

More information

Item ID: 57556
DC Identifier: http://oa.upm.es/57556/
OAI Identifier: oai:oa.upm.es:57556
Deposited by: Biblioteca ETSI Agrónomos
Deposited on: 18 Dec 2019 13:19
Last Modified: 18 Dec 2019 13:19
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