The Rhythmicity of Clock Genes is Disrupted in the Choroid Plexus of the APP/PS1 Mouse Model of Alzheimer’s Disease

Aug 4, 2020Journal of Alzheimer's disease : JAD

Daily Patterns of Biological Clock Genes Are Disrupted in the Fluid-Making Brain Region of an Alzheimer's Mouse Model

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Abstract

Dysregulation of circadian rhythmicity of Bmal1 expression was observed in 12-month-old APP/PS1 transgenic mice.

Circadian rhythm disruption is closely associated with Alzheimer's disease pathology.
Core-clock gene expression was evaluated in APP/PS1 mouse models at different ages.
A significant dysregulation of Bmal1 expression was found in both female and male transgenic mice.
Male APP/PS1 mice also exhibited a dysregulation of Period 2 (Per2) expression.
Melatonin pre-treatment influenced the circadian expression pattern of Bmal1 in the brain.

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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.

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The Rhythmicity of Clock Genes is Disrupted in the Choroid Plexus of the APP/PS1 Mouse Model of Alzheimer’s Disease

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