S9.2 Autonomic dysfunction in the Parkinson's disease clinic

Abstracts / Autonomic Neuroscience: Basic and Clinical 149 (2009) 1–126

Spinal/vagal fibres: None of the labelled fibres examined contained NOS-immunoreactivity (0 of 52 labelled fibres). Non TH- and NOS-immunoreactive varicosities made en passant contacts with nitrergic myenteric nerve cell bodies (4.5%; 6 of 132 NOS cells from 26 ganglia). Flattened lamellar endings similar to previously described rectal intraganglionic laminar endings [3] were observed. Additionally, specialized nerve endings (non TH- and NOS-immunoreactive) that have not been previously reported in vagal innervation were identified. These included dense and large varicosities forming circular arrangements around an individual myenteric cell body. These specialized endings may represent a subset of spinal sensory neurons that do not contain NOS or from vagal efferents. [1] Tassicker, B.C., Hennig, G.W., Costa, M., Brookes, S.J.H., 1999 Rapid anterograde and retrograde tracing from mesenteric nerve trunks to the guinea-pig small intestine in vitro. Cell Tissue Res 295, 437–452. [2] Tan, L.L., Bornstein, J.C., Anderson, C.R., 2008. Distinct chemical classes of medium-sized transient receptor potential channel vanilloid 1-immunoreactive dorsal root ganglion neurons innervate the adult mouse jejunum and colon. Neuroscience 156, 334–343. [3] Olsson, C., Costa, M., Brookes, S.J.H., 2004. Neurochemical characterization of extrinsic innervation of the guinea pig rectum. J Comp Neurol 470, 357–371. Acknowledgements: The work was supported in part by a grant from the National Health and Medical Research Council of Australia (Grant 400053).

S9.2 Autonomic dysfunction in the Parkinson's disease clinic

doi:10.1016/j.autneu.2009.05.045

doi:10.1016/j.autneu.2009.05.047

S9. Autonomic disorders in Parkinson's disease

S9.3 Autonomic dysfunction in mice overexpressing human wildtype alpha synuclein

S9.1 Neuropathology in the autonomic system in patients with Parkinson's disease G.M. Halliday (Prince of Wales Medical Research Institute and the University of New South Wales, Sydney Australia) Until recently Parkinson's disease (PD) was considered a disorder that mainly affected basal ganglia dopamine systems, as this region consistently degenerates in PD (>70% cell loss) and patients can be effectively treated with dopamine replacement therapies. However, much more widespread pathology occurs in PD with a number of authors suggesting that the autonomic system is affected prior to symptom onset by the pathological deposition of alpha-synuclein protein. It is currently hypothesised that pathology in the dorsal motor nucleus of the vagus nerve spreads both centrally and peripherally to induce the characteristic features of PD. Most patients with PD have significant protein deposition in parasympathetic vagal motor neurons and axons, but cell loss in this area is not pronounced until late in typical PD (50% loss). There is also early cardiac sympathetic dennervation, although robust clinical correlates remain illusive. Widespread protein deposition occurs throughout the peripheral nervous system as well as in the sympathetic intermediolateral cell column of the spinal cord, with skin biopsies in PD patients showing autonomic dennervation of blood vessels, sweat glands and erector pili muscles compared to controls. Careful analysis has shown that autonomic dennervation occurs due to protein aggregation initially in distal axonal processes prior to spreading centrally to the neuronal somata and neurites. Interestingly, neuronal somata remain intact for a considerable period in time following significant distal axonal pathology. The mechanism that spreads alpha-synuclein protein aggregation throughout the autonomic system and then within interconnected brain regions remains elusive, but an age-associated prion-like process cannot be ruled out. doi:10.1016/j.autneu.2009.05.046

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D.B. Rowe (Australian School of Advanced Medicine and Macquarie University, Sydney Australia) Although Parkinson's disease (PD) is principally considered to be a disorder that mainly affects basal ganglia dopaminergic systems, many other central and peripheral systems are involved. While dopamine replacement therapies are the mainstay of therapy including levodopa, dopamine agonists and inhibitors of dopamine metabolism, other approaches need to be considered in the wholistic management of patients with PD. Autonomic dysfunction is common in patients with PD, including postural hypotension, disturbances of bladder, intestinal and sexual function as well as sweating and skin abnormalities. While these autonomic features are usually a manifestation of symptomatic PD present for several years, prominent early dysautonomia should prompt the clinician to reconsider the diagnosis of PD. While the literature on dopamine replacement therapy is considerable, there is very little literature on the therapeutic approaches to autonomic dysfunction in PD. In addition, with the advent of therapeutic options to manage the motor dysfunction in advanced PD, such as deep brain stimulation, the appropriate management of autonomic dysfunction will assume greater importance. An approach to autonomic dysfunction in the PD Clinic, together with the literature underpinning this approach will be presented.

S.M. Fleming (Department of Neurology, University of California Los Angeles, Los Angeles, CA 90095, USA), L. Wang (CURE/Digestive Diseases Center and Center for Neurobiology of Stress, VAGLAHS, Los Angeles, CA 90073, USA), M.C. Jordan (Department of Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA), K.P. Roos (Department of Physiology, University of California Los Angeles, Los Angeles, CA 90095, USA), E. Masliah (Department of Neuroscience, University of California San Diego, La Jolla, CA 92093, USA), Y. Taché (CURE/Digestive Diseases Center and Center for Neurobiology of Stress, VAGLAHS, Los Angeles, CA 90073, USA), M.-F. Chesselet (Department of Neurology, University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Neurobiology, University of California Los Angeles, Los Angeles, CA 90095, USA) Autonomic dysfunction is a common non-motor symptom associated with synucleinopathies such as Parkinson's disease (PD). Both gastrointestinal and cardiovascular autonomic dysfunction occurs frequently in PD and includes impairments in colonic motility, constipation, orthostatic hypotension, and sympathetic denervation. In addition, Lewy body pathology has been shown in both peripheral and central nervous system areas associated with autonomic function. In many cases these symptoms appear to develop prior to the onset of motor symptoms making autonomic dysfunction an ideal target for potential neuroprotective treatments and the development of biomarkers for synucleinopathies. The presynaptic protein alpha synuclein has been implicated in familial forms of PD and is a major component of Lewy bodies, the pathological hallmark of sporadic PD. Transgenic mice that overexpress alpha synuclein under the Thy1 promoter (Thy1-aSyn) have high levels of alpha synuclein expression throughout the brain including the cortex, thalamus, substantia nigra, and brainstem [1], and they exhibit proteinase K-resistant alpha synuclein aggregates in the substantia nigra, locus coeruleus, and olfactory bulb. Behaviorally, they display early and progressive alterations in sensorimotor function [2] and impairments in olfaction [3] another early non-motor symptom