Sleep Deprivation May Amplify Cognitive and Emotional Issues in Parkinson’s, Study Finds

Not getting enough sleep may cause memory defects and emotional changes in Parkinson’s disease due to changes in dopamine metabolism, according to a study of zebrafish.

The study, “Sleep Deprivation caused a Memory Defects and Emotional Changes in a Rotenone-based Zebrafish Model of Parkinson’s Disease,” was published in Behavioural Brain Research.

Most Parkinson’s patients experience disease-related non-motor symptoms often preceding the onset of hallmark motor signs. Some of Parkinson’s non-motor symptoms include anxiety, apathy, mood changes, cognitive impairment and emotional disorders, which individually or taken together eventually affect patients’ quality of life.

“In addition to cognitive and emotional disorders, sleep abnormalities are also prevalent in [Parkinson’s disease],” the researchers wrote. “The problem of sleep is not only the characteristics of the disease itself, but also related to medication and dyskinesia such as tremor and rigidity.”

Sleep is an essential physiological process, and lack or shortage of sleep time causes fatigue, increase of mood swings, and can affect learning and memory. Some studies have shown that sleep deprivation can result in emotional and cognitive impairments.

Now, a team of Chinese researchers investigated the effects of sleep deprivation on locomotor activity, memory and emotional behavior in a zebrafish model of Parkinson’s disease.

To mimic the neurodegenerative disorder, animals were given rotenone — a pesticide that inhibits function of mitochondria (cells’ powerhouses) — which leads to cellular death and onset of parkinsonian features. People who come in contact with rotenone are at an increased risk of developing Parkinson’s disease.

Zebrafish were deprived of sleep for four weeks by being in an aquarium with around-the-clock lighting. Of note, fish usually are exposed to 10 hours of “lights off” a day. Rotenone-treated and sleep-deprived animals’ results were compared to control animals who were not given rotenone.

Rotenone-treated zebrafish exhibited parkinsonian-like symptoms, particularly slowness of movement. Motor symptoms’ progression was not aggravated by sleep deprivation.

Rotenone treatment alone impaired the zebrafishs’ memories. Compared to control animals, animals treated with rotenone that were sleep deprived had trouble memorizing and discerning similar objects that were presented to them, suggesting sleep deprivation further damages short-term cognitive deficits.

Not getting enough sleep also was found to worsen anxiety and depression-like behavior in the rotenone treated animals.

Scientists then sought to understand if the observed behavioral changes could  be related to the metabolism of dopamine – the chemical messenger that’s in short supply in Parkinson’s disease.

When compared to control animals, those treated with rotenone had lower levels of dopamine in the brain. However, sleep deprivation did not decrease dopamine concentrations any further. DOPAC, the principal metabolite (i.e., product of metabolism) of dopamine, which was reduced after rotenone treatment alone, had its levels restored upon sleep deprivation.

High levels of two types of dopamine receptors (to which dopamine binds), specifically D2 and D3, were observed in rotenone-treated zebrafish, in comparison to the control group. Interestingly, the levels of those same receptors significantly decreased after sleep deprivation.

Dopamine metabolism appears to be altered in rotenone-treated animals and sleep deprivation seems to play a part in such alteration, however there is not a clear understanding as to how this happens yet.

“[Z]ebrafish displayed an anxiety-depressed mood and a decline in memory after [exposure] to Rotenone, and sleep deprivation caused more severe phenotype [disease characteristics] in this model via altering the [dopamine] metabolism and D2 and D3 receptors,” the researchers wrote. “Our studies not only provided the understanding the roles of [sleep deprivation] in PD non-motor dysfunctions, but also provided a useful model for future pathogenesis and therapeutic studies,” they concluded.