The Rhythmicity of Clock Genes is Disrupted in the Choroid Plexus of the APP/PS1 Mouse Model of Alzheimer's Disease.
ARNTL Transcription Factors
/ genetics
Alzheimer Disease
/ genetics
Amyloid beta-Protein Precursor
/ genetics
Animals
CLOCK Proteins
/ genetics
Cell Line, Transformed
Choroid Plexus
/ pathology
Circadian Rhythm
/ physiology
Female
Humans
Male
Mice
Mice, Transgenic
Periodicity
Presenilin-1
/ genetics
Rats
Alzheimer’s disease
amyloid-β
blood-cerebrospinal fluid barrier
choroid plexus
circadian clock
melatonin
Journal
Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863
Informations de publication
Date de publication:
2020
2020
Historique:
pubmed:
4
8
2020
medline:
10
9
2021
entrez:
4
8
2020
Statut:
ppublish
Résumé
The choroid plexus (CP), which constitutes the blood-cerebrospinal fluid barrier, was recently identified as an important component of the circadian clock system. 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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 32741824
pii: JAD200331
doi: 10.3233/JAD-200331
doi:
Substances chimiques
ARNTL Transcription Factors
0
Amyloid beta-Protein Precursor
0
Bmal1 protein, mouse
0
Presenilin-1
0
CLOCK Proteins
EC 2.3.1.48
Clock protein, mouse
EC 2.3.1.48
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM