Neurotoxic lesions at the ventral mesopontine junction change sleep time and muscle activity during sleep: An animal model of motor disorders in sleep

• Published in: Neuroscience 2008-06, Vol.154 (2), p.431-443
• Main Authors: Lai, Y.-Y, Hsieh, K.-C, Nguyen, D, Peever, J, Siegel, J.M
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; Brain Stem - physiology; Cats; Data Interpretation, Statistical; Disease Models, Animal; Electric Stimulation; Electroencephalography; Excitatory Amino Acid Agonists - toxicity; Female; Male; Motor Activity - physiology; Movement - physiology; Muscle, Skeletal - physiopathology; N-Methylaspartate - toxicity; Neurology; Parkinsonism; periodic leg movements; Polysomnography; pons; Pons - physiology; REM sleep behavior disorder; retrorubral nucleus; Sleep - drug effects; Sleep Wake Disorders - chemically induced; Sleep Wake Disorders - physiopathology; Sleep Wake Disorders - psychology; substantia nigra
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.03.085

Abstract There is no adequate animal model of restless legs syndrome (RLS) and periodic leg movements disorder (PLMD), disorders affecting 10% of the population. Similarly, there is no model of rapid eye movement (REM) sleep behavior disorder (RBD) that explains its symptoms and its link to Parkinsonism. We previously reported that the motor inhibitory system in the brainstem extends from the medulla to the ventral mesopontine junction (VMPJ). We now examine the effects of damage to the VMPJ in the cat. Based on the lesion sites and the changes in sleep pattern and behavior, we saw three distinct syndromes resulting from such lesions; the rostrolateral, rostromedial and caudal VMPJ syndromes. The change in sleep pattern was dependent on the lesion site, but was not significantly correlated with the number of dopaminergic neurons lost. An increase in wakefulness and a decrease in slow wave sleep (SWS) and REM sleep were seen in the rostrolateral VMPJ-lesioned animals. In contrast, the sleep pattern was not significantly changed in the rostromedial and caudal VMPJ-lesioned animals. All three groups of animals showed a significant increase in periodic and isolated leg movements in SWS and increased tonic muscle activity in REM sleep. Beyond these common symptoms, an increase in phasic motor activity in REM sleep, resembling that seen in human RBD, was found in the caudal VMPJ-lesioned animals. In contrast, the increase in motor activity in SWS in rostral VMPJ-lesioned animals is similar to that seen in human RLS/PLMD patients. The proximity of the VMPJ region to the substantia nigra suggests that the link between RLS/PLMD and Parkinsonism, as well as the progression from RBD to Parkinsonism may be mediated by the spread of damage from the regions identified here into the substantia nigra.