Sleep disturbances may play a role in Alzheimer’s pathogenesis

Aaradhana Natarajan, 2020

Caption: Mice brains are similar to humans, with study results suggesting that sleep disturbances can lead to the formation of neurodegenerative plaques.

Caption: Mice brains are similar to humans, with study results suggesting that sleep disturbances can lead to the formation of neurodegenerative plaques.

Alzheimer’s Disease is a neurodegenerative condition that has recently become a popular focus for research. As a result, scientists are now aware that the accumulation of amyloid-β-peptide oligomers (AβOs) play a central role in Alzheimer’s pathogenesis. However, the effect of sleep disturbances on Alzheimer’s risk is relatively underknown. This knowledge gap spurred Dr. Grasielle Kincheski and her team at the Federal University of Rio de Janeiro to investigate potential links between sleep disturbances and neurodegeneration.

The research used a cohort of male Swiss mice, divided into three groups. There was a paradoxical sleep deprivation condition (PSD), a chronic sleep restriction condition (CSR), and a control group. The PSD group underwent the multiple platforms deprivation method introduced in Van Hulzen and Coenen’s 1980 study for 72 hours, while the CSR group was restricted from sleeping between 1-4 pm, five days a week, for a month. The CSR group was kept awake by light brushing every time they demonstrated drowsiness. Some of the individuals in each of the three groups were also given injections of AβOs, to see if sleep disturbances impacted plaque growth.

After the period of sleep disturbance, the animals were tested for motor and memory capacity, as well as plasma coticosterone levels and responsiveness to fear stimuli. The PSD mice showed reduced responsiveness to fear stimuli and reduced memory for familiar objects. They also demonstrated a significant increase in corticosterone levels, suggesting an impaired stress response. The CSR mice, on the other hand, only demonstrated an impaired fear response. These mice did not have any significant difference in memory performance or corticosterone levels, compared to control mice. Interestingly, neither the PSD not the CSR mice showed significant changes in motor behaviors.

When considering the injections, researchers noted that PSD mice infused with 100 pmol of AβOs spent less time asleep than other mice. CSR mice also demonstrated a reduction in hippocampal synaptophysin and PSD-95, which are indicators of synaptic density. Decreases in these compounds suggest synaptic degeneration and memory loss. The effect on sleep-deprived mice was greater than those of the controls, with memory impairment persisting even after a week-long recovery period at the end of the restriction period. It is thus likely that sleep deprivation furthers the accumulation of AβOs in the brain, leading to Alzheimer’s.

There were certain limitations to the study. For example, the researchers used only male mice, though there is some indication that both sex and age impact dementia risk. Also, aging in humans can lead to sleep disturbances independent of environment, which could also affect the formation of AβO oligomers in brain tissue. Regardless, the new insight into sleep as a factor in Alzheimer’s risk can lead to more effective therapies and preventive protocols for aging individuals.

 

Sources

  1. Kincheski, G., et al. (2017). Chronic sleep restriction promotes brain inflammation and synapse loss, and potentiates memory impairment induced by amyloid-β oligomers in mice. Brain, Behavior, and Immunity.
  2. Van Hulzen, Z. J. M., & Coenen, A. M. L. (1980). The pendulum technique for paradoxical sleep deprivation in rats. Physiology & behavior25(6), 807-811.
  3. 3. Image retrived from: https://www.flickr.com/photos/e3000/99786620
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