Impaired Parasympathetic Activity Research Articles

Autonomic Nervous System Disorders in Parkinson’s Disease

This paper gives a review on the clinical features of autonomic failure which occur in idiopathic Parkinson's disease (PD), mainly based on the recent publications, especially from Japan. In 1817, James Parkinson already mentioned bowel and bladder dysfunctions in his original article. Since then, a number of clinical studies have disclosed the occurrence of autonomic failure in this disease. It is known that relatively minor degrees of orthostatic hypotension are not rare, but other features of autonomic failure are rather uncommon, generally mild in severity and nonprogressive. Orthostatic hypotension is suggested as a possible side effect of L-dopa. Postprandial hypotension is occasionally found, and vasopressin is proven to prevent it remarkably. There is low electrocardiographic R-R interval variability which indicates impaired parasympathetic activity. Thermoregulatory sweating is nearly normal, but its center is functionally impaired. Resting skin temperature is slightly lower. Both salivation and lacrymation are quantitatively within normal limits. Little is known on sexual function in PD.

Focus: The wrong doctors: selection or training at fault?

<h3>Background</h3> Pathogenic variants of <i>GNB5</i> encoding the β₅ subunit of the guanine nucleotide-binding protein cause IDDCA syndrome, an autosomal recessive neurodevelopmental disorder associated with cognitive disability and cardiac arrhythmia, particularly severe bradycardia. <h3>Methods</h3> We used echocardiography and telemetric ECG recordings to investigate consequences of <i>Gnb5</i> loss in mouse. <h3>Results</h3> We delineated a key role of <i>Gnb5</i> in heart sinus conduction and showed that <i>Gnb5</i>-inhibitory signalling is essential for parasympathetic control of heart rate (HR) and maintenance of the sympathovagal balance. <i>Gnb5^−/−</i> mice were smaller and had a smaller heart than <i>Gnb5^+/+</i> and <i>Gnb5^+/−</i>, but exhibited better cardiac function. Lower autonomic nervous system modulation through diminished parasympathetic control and greater sympathetic regulation resulted in a higher baseline HR in <i>Gnb5^−/−</i> mice. In contrast, <i>Gnb5^−/−</i> mice exhibited profound bradycardia on treatment with carbachol, while sympathetic modulation of the cardiac stimulation was not altered. Concordantly, transcriptome study pinpointed altered expression of genes involved in cardiac muscle contractility in atria and ventricles of knocked-out mice. Homozygous <i>Gnb5</i> loss resulted in significantly higher frequencies of sinus arrhythmias. Moreover, we described 13 affected individuals, increasing the IDDCA cohort to 44 patients. <h3>Conclusions</h3> Our data demonstrate that loss of negative regulation of the inhibitory G-protein signalling causes HR perturbations in <i>Gnb5⁻</i>^/− mice, an effect mainly driven by impaired parasympathetic activity. We anticipate that unravelling the mechanism of <i>Gnb5</i> signalling in the autonomic control of the heart will pave the way for future drug screening.