The Rhythmicity of Clock Genes is Disrupted in the Choroid Plexus of the APP/PS1 Mouse Model of Alzheimer’s Disease
Autor: | Eva Carro, Rosario Astaburuaga, Angela Relógio, José Cipolla-Neto, Ana Paula Cabral Seixas Costa, Isabel Gonçalves, Telma Quintela, Manuel C. Lemos, Cecília R.A. Santos, Ana Catarina Duarte, André Furtado |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Periodicity endocrine system medicine.medical_specialty Transgene Circadian clock CLOCK Proteins Mice Transgenic Stimulus (physiology) Biology Melatonin Amyloid beta-Protein Precursor Mice 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Internal medicine Presenilin-1 medicine Animals Humans Circadian rhythm Cell Line Transformed General Neuroscience EXPRESSÃO GÊNICA ARNTL Transcription Factors General Medicine Circadian Rhythm Rats CLOCK PER2 Psychiatry and Mental health Clinical Psychology 030104 developmental biology Endocrinology Choroid Plexus Female Choroid plexus Geriatrics and Gerontology 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
ISSN: | 1875-8908 1387-2877 |
DOI: | 10.3233/jad-200331 |
Popis: | Background: The choroid plexus (CP), which constitutes the blood-cerebrospinal fluid barrier, was recently identified as an important component of the circadian clock system. Objective: The fact that circadian rhythm disruption is closely associated to Alzheimer’s disease (AD) led us to investigate whether AD pathology can contribute to disturbances of the circadian clock in the CP. Methods: For this purpose, we evaluated the expression of core-clock genes at different time points, in 6- and 12-month-old female and male APP/PS1 mouse models of AD. In addition, we also assessed the effect of melatonin pre-treatment in vitro before amyloid-β stimulus in the daily pattern of brain and muscle Arnt-like protein 1 (Bmal1) expression. Results: Our results showed a dysregulation of circadian rhythmicity of Bmal1 expression in female and male APP/PS1 transgenic 12-month-old mice and of Period 2 (Per2) expression in male mice. In addition, a significant circadian pattern of Bmal1 was measured the intermittent melatonin pre-treatment group, showing that melatonin can reset the CP circadian clock. Conclusion: These results demonstrated a connection between AD and the disruption of circadian rhythm in the CP, representing an attractive target for disease prevention and/or treatment. |
Databáze: | OpenAIRE |
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