Friday, March 4, 2022

Circadian Rhythm Disruption and Alzheimer’s Disease

There are many different behavioral patterns of organisms that are under the control of 24-hour light-dark cycles called circadian rhythms. These circadian systems are responsible for biological and physiological outputs such as feeding behavior, sleeping, as well as hormone release and regulation. However, the genetic circuitry underlying circadian rhythms can easily be disrupted by factors such as light-noise, jet-lag, blue light, and a variety of other factors (Sharma et al., 2021). Circadian rhythm disruptions are shown to be detrimental to both behavioral output and cognitive function. 

Circadian systems play a large role in hippocampal memory formation, which is influenced by the GABA hormone released from the suprachiasmatic nucleus (SCN) (Ruby et al., 2008). In the article, “Circadian Rhythm Disruption and Alzheimer’s Disease: The Dynamics of a Vicious Cycle.”, Sharma et al. investigate how circadian rhythm disruptions contribute to Alzheimer’s disease (AD). Alzheimer’s is characterized by a loss of memory and cognitive function, with postmortem analysis of AD brains revealing desynchronized central circadian clock expression and disrupted hormone cycles (Cermakian et al., 2011). Transgenic mice mimicking the circadian rhythm disruption of jet-lag exhibited significant memory impairment and hippocampal neurogenesis compared to the memory performance of control mice. Furthermore, realignment of disrupted circadian systems were found to improve some of the cognitive symptoms exhibited in patients with advanced AD (Sharma et al., 2021). This study indicates that the pathology of AD is supported and reinforced by disruptions to the genetic mechanisms underlying circadian rhythms.          

A similar study titled “Central and Peripheral Clock Control of Circadian Feeding Rhythms” by Fulgham et al. explores the effect of molecular circadian clock manipulations on the feeding behavior of fruit flies, or Drosophila melanogaster. The researchers determined that the molecular clocks in both brain and peripheral tissues are largely responsible for feeding rhythms. Central brain clocks were found to dictate the ultimate timing of feeding rhythms, unlike the fat body clocks in peripheral tissue. When the molecular clocks in multiple peripheral cells were disrupted, fruit flies consumed less and had a reduced feeding rhythm strength (Fulgham et al., 2021). Ultimately, this study demonstrates how disruptions to circadian rhythms can be detrimental to important biological processes such as food intake.

Both studies reveal the importance of circadian rhythms and how they can greatly influence the overall health of an organism. While some believe exchanging sleep for another activity may be beneficial, it will ultimately have greater long-term impacts. Circadian rhythm disruptions can have extreme adverse biological and physiological effects, indicating how critical it is to have healthy sleep habits. It is the active implementation of these habits that can potentially realign disrupted circadian rhythms and help improve overall quality of life.   

                           

References

Cermakian, Nicolas et al. “Circadian clock gene expression in brain regions of Alzheimer 's disease patients and control subjects.” Journal of biological rhythms vol. 26,2 (2011): 160-70. doi:10.1177/0748730410395732

Fulgham, C.V., Cavanaugh, D.J., et al. “Central and Peripheral Clock Control of Circadian Feeding Rhythms.” Journal of Biological Rhythms, vol. 36, no. 6, SAGE Publications, 2021, pp. 548–566., https://doi.org/10.1177/07487304211045835.

Ruby, N.F. et al. “Hippocampal-dependent learning requires a functional circadian system.” Proceedings of the National Academy of Sciences of the United States of America vol. 105,40 (2008): 15593-8. doi:10.1073/pnas.0808259105

Sharma, Ashish, et al. “Circadian Rhythm Disruption and Alzheimer’s Disease: The Dynamics of a Vicious Cycle.” Current neuropharmacology 19, no. 2 (2021): 248–264., https://doi.org/10.2174/1570159X18666200429013041.






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