Our body is tuned to function in a synchronous manner with a
“circadian” or day-and-night rhythm. Alterations to daily lifestyles due
to the current stressful routines people follow can disrupt the body’s
day-night cycle for longer periods.
Recent studies in
rats have shown that even chronic light exposure can disrupt the
circadian rhythm and cause memory deficits seen in neurological
disorders such as Alzheimer disease. Interestingly, circadian
rhythm disruption has also been frequently reported in patients
suffering from Alzheimer disease.
However, the cause-and-effect relationship between Alzheimer disease and circadian rhythm disruption remains unclear.
understand the correlation between circadian rhythm disturbances and Alzheimer disease 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.
Explaining the rationale behind their study published in ACS Chemical Neuroscience,
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 Alzheimer disease.”
In a previous study, the team had 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 Alzheimer disease. Building on these findings, they
speculated that longer light exposure may result in circadian rhythm
disruptions that cause an Alzheimer diseaselike phenotype.
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 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.
including glutamate and γ-aminobutyric acid, were dysregulated in the
SCN of rats with circadian rhythm disruption due to chronic light
exposure. Additionally, these animals showed disrupted metabolic
profiles, suggestive that their digestive systems may also have been
adversely affected by the disrupted circadian rhythms.
of soluble Aβ in the brain was also significantly higher in these rats
compared to the controls, and they experienced down-regulation of
anti-aging gene Sirt1 and up-regulation of the neuronal damage markers.
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 Alzheimer disease-like phenotype.
on the above results, their next hypothesis was that fluoxetine, a drug
used for treating anxiety and hyperactivity, could alleviate
physiological and functional abnormalities associated with circadian
rhythm disruption. Sure enough, fluoxetine treatment prevented oxidative
damage, Aβ accumulation, and rescued memory and cognitive deficits in
the treated rats.
Overall, the study suggests that long-term circadian rhythm disruption induces Alzheimer disease-like pathology in rats, which can be prevented by treatment with fluoxetine. Notably, elevation in Aβ, a hallmark of Alzheimer disease, and disturbed circadian rhythms, can each trigger the other, resulting in a cascade of irreversible neurological symptoms. This sets the stage for serious life-long conditions like Alzheimer disease.
The clinical implications of their findings are also evident.
Goyal remarks, “Lifestyle changes that support exposure to natural
light followed by ample rest at night may thus be key to limiting the
risk of neurological disorders. Therapeutic strategies to optimize
circadian timing in prospective patients hold great promise to restrain
the prevalence of Alzheimer disease.”
Better lifestyle practices, following the
traditional Indian discipline of yoga, or maintaining a natural
day-night cycle for work schedules and even dietary practices may make
our bodies healthier and function better.
This study certainly
“sheds light” on the cause-and-effect relationship between circadian
rhythms and Alzheimer disease progression, paving the way for future investigations on
this important topic.
Source: News Release
August 19, 2021