The role of orexin in Parkinson's disease.

Emerging evidence has implicated the orexin system in non-motor pathogenesis of Parkinson's disease. It has also been suggested the orexin system is involved in the modulation of motor control, further implicating the orexin system in Parkinson's disease. Parkinson's disease is the second most common neurodegenerative disease with millions of people suffering worldwide with motor and non-motor symptoms, significantly affecting their quality of life. Treatments are based solely on symptomatic management and no cure currently exists. The orexin system has the potential to be a treatment target in Parkinson's disease, particularly in the non-motor stage. In this review, the most current evidence on the orexin system in Parkinson's disease and its potential role in motor and non-motor symptoms of the disease is summarized. This review begins with a brief overview of Parkinson's disease, animal models of the disease, and the orexin system. This leads into discussion of the possible roles of orexin neurons in Parkinson's disease and levels of orexin in the cerebral spinal fluid and plasma in Parkinson's disease and animal models of the disease. The role of orexin is then discussed in relation to symptoms of the disease including motor control, sleep, cognitive impairment, psychological behaviors, and the gastrointestinal system. The neuroprotective effects of orexin are also summarized in preclinical models of the disease.

Role of the Adrenal Medulla in Hypoglycaemia-Associated Autonomic Failure-A Diabetic Perspective.

Hypoglycaemia-associated autonomic failure (HAAF) is characterised by an impairment in adrenal medullary and neurogenic symptom responses following episodes of recurrent hypoglycaemia. Here, we review the status quo of research related to the regulatory mechanisms of the adrenal medulla in its response to single and recurrent hypoglycaemia in both diabetic and non-diabetic subjects with particular focus given to catecholamine synthesis, enzymatic activity, and the impact of adrenal medullary peptides. Short-term post-transcriptional modifications, particularly phosphorylation at specific residues of tyrosine hydroxylase (TH), play a key role in the regulation of catecholamine synthesis. While the effects of recurrent hypoglycaemia on catecholamine synthetic enzymes remain inconsistent, long-term changes in TH protein expression suggest species-specific responses. Adrenomedullary peptides such as neuropeptide Y (NPY), galanin, and proenkephalin exhibit altered gene and protein expression in response to hypoglycaemia, suggesting a potential role in the modulation of catecholamine secretion. Of note is NPY, since its antagonism has been shown to prevent reductions in TH protein expression. This review highlights the need for further investigation into the molecular mechanisms involved in the adrenal medullary response to hypoglycaemia. Despite advancements in our understanding of HAAF in non-diabetic rodents, a reliable diabetic rodent model of HAAF remains a challenge.

Time use and dimensions of healthy sleep: A cross-sectional study of Australian children and adults.

BACKGROUND: Sleep is increasingly recognized as a multidimensional construct that occurs within the 24-hour day. Despite advances in our understanding, studies continue to consider the relationship between sleep, sedentary time and physical activity separately, and not as part of the 24-hour day. AIMS: To determine the association between the 24-hour activity composition and dimensions of healthy sleep. METHODS: This study examined data on 1168 children (mean age 12years; 49% female) and 1360 adults (mean age 44years; 87% female) collected as part of the Child Health CheckPoint study. Participants were asked to wear a GENEActiv monitor (Activinsights, Cambs, UK) on their nondominant wrist for eight consecutive days to measure 24-hour time-use. Compositional data analysis was used to examine the association between time use (actigraphy-derived sleep duration, sedentary time, light physical activity and moderate-vigorous physical activity) and dimensions of healthy sleep. Healthy sleep was conceptualized in terms of continuity/efficiency, timing, alertness/sleepiness, satisfaction/quality, and regularity. Time allocations were also examined. RESULTS: The 24-hour activity composition was significantly associated with all objectively measured and self-report dimensions of healthy sleep in both children and adults. Allocating more time to sleep was associated with earlier sleep onsets, later sleep offsets, less efficient and more consistent sleep patterns for both children and adults. CONCLUSION: This study highlights the integral relationship between daily activities and dimensions of sleep. Considering sleep within the 24-hour day activity composition framework may help inform lifestyle decisions to improve sleep health.