Aszensionshypothese beim idiopathischen Parkinson-Syndrom

Zusammenfassung

Patienten mit idiopathischem Parkinson-Syndrom (IPS) durchlaufen verschiedene klinische Stadien, wobei nicht-motorische Symptome insbesondere die prodromale Phase der Parkinson-Erkrankung bestimmen, während die motorischen Kardinalsymptome wie die Bradykinese mit Rigidität, Ruhetremor oder posturaler Instabilität zwingend für die klinische Diagnosestellung des IPS notwendig sind. Wichtige frühe nicht-motorische Symptome sind die Riechstörung, Obstipation, Depression und Schlafstörungen. Entsprechend des klinischen Verlaufs postulieren die Braak-Stadien, dass der neuropathologische Prozess der Parkinson-Erkrankung im enterischen Nervensystem (ENS) des gastrointestinalen Systems und im Bulbus olfactorius beginnt. Es kommt anschließend durch transsynaptischen Zell-zu-Zell-Transport zu einem rostrokraniellen Aufstieg der Parkinson-Pathologie via sympathisches und parasympathisches Nervensystem. Mit Erreichen des zentralen Nervensystems treten die für das IPS pathognomischen Veränderungen mit selektiver Degeneration der dopaminergen Neurone in der Substantia nigra pars compacta, dem Nachweis von Lewy-Körperchen, eine reaktive Gliose und eine fortschreitende zentrale Neurodegeneration auf. Die diesen Hypothesen zugrunde liegenden klinischen und pathologischen sowie Tierversuchsstudien werden in diesem Übersichtsartikel dargestellt. So konnte α-Synuclein als die Parkinson-spezifische Pathologie im Bulbus olfactorius, im ENS, in der Glandula submandibularis, im intermediolateralen Nucleus des Rückenmarks und im dorsalen motorischen Nucleus des Nervus vagus nachgewiesen werden. Mittels eines Tiermodelles, bei dem Mäuse chronisch intragastral das Pestizid Rotenon erhalten, konnten wir für das IPS klassische pathologische Veränderungen, die Entwicklung von Parkinson-Symptomen und auch einen spezifischen zeitlichen und räumlichen Ablauf der Parkinson-Pathologie auslösen.

Abstract

Different clinical stages are observed in idiopathic Parkinsonʼs disease (PD). Non-motor symptoms define the prodromal period of PD in particular whereas 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. When the central nervous system is reached, the 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.

Schlüsselwörter

Parkinson-Syndrom - Lewy-Körperchen - Aszensionshypothese - enterisches Nervensystem - nicht-motorische Symptome

Key words

Parkinsonʼs disease - Lewy body - ascension hypothesis - enteric nervous system - non-motor symptoms

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