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Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis.
Brown MK1, Chan MT1, Zimmerman JE1, Pack AI2, Jackson NE1, Naidoo N3.
Author information
1
Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, PA, USA.
2
Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, PA, USA; Division of Sleep Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
3
Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, PA, USA; Division of Sleep Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: naidoo@mail.med.upenn.edu.
Abstract
Alterations in the quality, quantity, and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response. The effectiveness of the adaptive unfolded protein response is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of X-box binding protein 1 and upregulation of phosphorylated elongation initiation factor 2 a, in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged or sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep or sleep debt discharge.
To summarize, our data indicate that the ER stress response is compromised with aging and that the additional challenge of sleep deprivation further exacerbates ER stress and leads to induction of proapoptotic signaling.
Apathy and Depression Linked to Sleep Disorder in Parkinson’s Patients, Study Finds
Symptoms of apathy and depression are more frequent and severe in Parkinson’s patients with rapid eye movement sleep behavior disorder (RBD) than in patients without this disorder, according to a study.
Findings also showed that women with Parkinson’s and RBD are more likely to experience apathy than men.
The study, “Apathy in Parkinson’s disease with REM sleep behavior disorder,” was published in the Journal of the Neurological Sciences.
RBD affects up to half of Parkinson’s patients and often appears several years before motor symptoms. People with Parkinson’s and RBD typically experience more non-motor symptoms such as cognitive impairment, daytime sleepiness, and depression than those without RBD.
Apathy is very common in Parkinson’s patients and affects the treatment and long-term outcomes of the disease. Recent evidence showed a high prevalence of apathy in people with RBD and depression, but studies on the association between these disorders in Parkinson’s patients are still lacking.
Researchers at the University of Bern in Switzerland addressed this shortcoming by analyzing the motor function of 64 Parkinson’s patients, using the modified Hoehn & Yahr stage and the Unified Parkinson’s Disease Rating Scale (on and off dopaminergic medication), prior to deep brain stimulation from 2012 to 2016.
Non-motor assessments included the Starkstein apathy scale (SAS), the Hamilton depression rating scale, the Epworth sleepiness scale, and the mini-mental state examination of cognitive impairment. No patient had relevant cognitive deterioration or dementia.
Of the patients, 26 (40%) fulfilled the criteria for RBD (mean age of 62.6 years, Parkinson’s duration of 12.8 years), while 38 did not (mean age of 63 years, disease duration of 11.4 years). Motor function of the two groups only differed in the UPDRS part 2 score, related to daily living activities. This score was higher in patients with RBD when specifically analyzing the periods they were off medication.
Among the patients with RBD, 52% had apathy, defined as a score of 14 or higher on the SAS, while 50% had more symptoms of depression. In the group without RBD, apathy was observed in 42% of patients and depressive symptoms in 20% of them.
Patients with RBD had significantly higher mean apathy and depression scores, indicating greater severity, than those without this disorder. Higher apathy scores were especially seen in women. In contrast, the results of sleepiness and cognitive function were similar between the two groups.
“In [Parkinson’s], RBD is associated with isolated apathy and increased severity of depressive symptoms, independent of medication, motor and other non-motor symptoms,” the researchers wrote.
As for patients without depression, an increased apathy score was found in 53% of those with RBD and 29% of those without RBD. The data also showed that 58% of those with RBD and 64% of those without RBD had increased depressive symptoms but not an increased apathy score.
According to the researchers, this finding means that although their overlap is well-known, “apathy should not be considered as a mere symptom of depression.”
In the group with RBD, women showed more frequent and more severe apathy, as well as more frequent use of antidepressants than men, but these were not statistically significant. However, gender was the only independent predictor of apathy in the group with RBD, with women having a higher risk. No other gender difference was found.
This study suggests that patients with Parkinson’s and RBD “should receive targeted medical attention to improve diagnosis, monitoring and management of neuropsychiatric symptoms and their consequences,” the researchers concluded.
The post Apathy and Depression Linked to Sleep Disorder in Parkinson’s Patients, Study Finds appeared first on Parkinson’s News Today.
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