To understand the correlation between circadian rhythm disturbances and AD progression, a team of researchers from Shoolini University, India, tested the effect of circadian rhythm disruption caused by chronic light exposure on the physiology and functional abilities of Wistar rats.
‘Disrupted circadian rhythm induces Alzheimer’s Disease pathology in rats, which can be prevented by treatment with fluoxetine.’
Professor Rohit Goyal, who led the study, said, “Cells of various organs in the body are synchronized to the day-night cycle, and release different biochemical substances including hormones in a time-specific manner. Untimely expression of these hormones can trigger anxiety, cognitive impairment, and memory loss, all symptoms of brain disorders such as AD”.
In a previous study, the team reported that upon chronic light exposure for two months, rats exhibit cognitive deficits along with sub-clinical accumulation of amyloid β (Aβ), the pathogenic protein known to form aggregates in AD.
Building on these findings, they speculated that longer light exposure may result in circadian rhythm disruptions that cause an AD-like phenotype. This rationale is published in journal ACS Chemical Neuroscience.
To test this hypothesis, they exposed adult rats to constant light conditions for four months and compared them with rats subjected to a normal light-dark cycle taken as the control group.They found that chronic light exposure disrupted the expression of genes like Per2 that follow circadian rhythms.
Markers of oxidative stress such as peroxiredoxins and neurotransmitters, including glutamate and γ-aminobutyric acid were also dysregulated in the suprachiasmatic nuclei (SCN) region of the brain in these rats, which is the primary controller of circadian rhythms in the body.
Additionally, these animals showed disrupted metabolic profiles, suggesting that their digestive systems may have been adversely affected by the disrupted circadian rhythms.
The researchers also found that circadian rhythm disruption due to chronic light exposure caused memory and cognitive deficits in the rats. Collectively, these findings were suggestive of an AD-like phenotype.
Based on the above results, researchers used fluoxetine, a drug used for treating anxiety and hyperactivity to alleviate physiological and functional abnormalities associated with circadian rhythm disruption.
Fluoxetine treatment prevented oxidative damage, Aβ accumulation, and rescued memory and cognitive deficits in the treated rats.
This study which sheds light on the relationship between disturbed circadian rhythm and AD progression, paving the way for future investigations on this important topic.
Source: Medindia
