Hypothesis of Ascension in Idiopathic Parkinson’s Disease

Abstract

AbstractDifferent clinical stages are observed in idiopathic Parkinson’s disease (PD). Non-motor symptoms define in particular the prodromal period of PD whereas primary motor symptoms such as bradykinesia with rigidity, resting tremor or postural instability are mandatory for the diagnosis of PD. Important non-motor symptoms are olfactory dysfunction, constipation, depression and sleep disturbances. Corresponding to the clinical course of PD, the Braak staging system postulates that the neuropathological process of PD starts in the enteric nervous system (ENS) of the gut and in the olfactory bulb. From there, Parkinson pathology spreads by transsynaptic cell-to-cell transfer via the sympathetic and parasympathetic nervous system in a rostrocranial direction. If the central nervous system is reached, typical neuropathological changes of PD with selective degeneration of dopaminergic neurons of the Substantia nigra pars compacta, the formation of Lewy bodies, reactive gliosis and progressive central neurodegeneration appear. Evidence of clinical, pathological and animal studies supporting these hypotheses are summarised in this review article. α-synuclein as PD-specific pathology was found in the olfactory bulb, the ENS, the submandibular gland, the intermediolateral nucleus of the spinal cord and the dorsal motor nucleus of the vagus nerve. In an animal model, in which mice are treated with the pesticide rotenone chronically and intragastrically, we could almost completely reproduce the typical pathological and clinical features of PD as well as their development in a chronological and regional sequence.