Neuropeptides and the Autonomic Nervous System in Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is a rare, multisymptomatic genetic disorder caused by the absence or dysfunction of specific genes on chromosome 15. The genetic abnormality is anticipated to cause a dysfunction of the hypothalamus, which is also central in the regulation of the autonomic nervous system (ANS). Typical symptoms of PWS indicating a hypothalamic dysfunction include muscular hypotonia, poor growth, short stature, and feeding difficulties in infancy, which in early childhood are replaced by hyperphagia, leading to a high risk of obesity. Other characteristics, such as sleep difficulties, altered pain perception, delayed gastric emptying and constipation, blood pressure irregularities and dysregulated stress response, altered temperature regulation, delayed pupillary reaction, and urine retention and incontinence, all indicate a dysfunction of ANS. The ANS is usually divided into three parts: the sympathetic nervous system (SNS), which activates the fight-or-flight response during stress; the parasympathetic nervous system (PNS), which promotes calm and digestion; and the independent enteric nervous system (ENS), which regulates the gastrointestinal tract. Noradrenaline is the main neurotransmitter for the SNS, and acetylcholine for the PNS, while the ENS is regulated mainly by acetylcholine and serotonin. However, the ENS is modulated by both the SNS and the PNS, as well as many neuropeptides. Peptides regulating behavior, metabolism, appetite, and satiety have been extensively studied in PWS. However, studies of the role of neuropeptides in regulating other autonomic functions are limited and remain poorly understood. This review aims to synthesize current evidence from both animal models and human studies to explore potential mechanisms by which neuropeptides may contribute to autonomic dysfunction in individuals with PWS.