A pinboard by
Rachel McQuade

Research Fellow, Florey Institute of Neuroscience and Mental Health


Parkinson's disease (PD) is the second most common neurological disease in Australia, affecting more than 80,000 people annually. Characterized by progressive degeneration of nigrostriatal dopaminergic neurons, PD is associated with motor impairments such as rigidity, resting tremor, postural instability, and bradykinesia as well as autonomic dysfunction, often presenting as gastrointestinal (GI) dysfunction. Between 80-90% of people with PD suffer from GI dysfunction, most commonly constipation which often precedes the onset of motor deficits by decades. GI dysfunction has been correlated with abnormalities in the enteric nervous system (ENS). Studies focusing on the ENS of patients with Lewy body diseases have found α­synuclein in the ENS of nearly every patient with PD. Neuronal loss and neurochemical changes have been observed in the ENS of patients with PD and a positive correlation between gut permeability and intestinal levels of α­synuclein has been observed in untreated patients with early PD. Enteric neurons, therefore, may be involved in gastrointestinal dysfunction and PD initiation and development. However, the relationship between ENS and central nervous system (CNS) deterioration, motor deficits and GI dysfunctions remains unclear. New evidence strongly suggests that the pathogenesis of PD involves trans-synaptic cell-to-cell transmission of PD pathology from the ENS via the vagus nerve to the CNS. The work outlined here aims to use mouse models of PD to systematically investigate structural and functional deterioration in the ENS and CNS to uncover the temporal and causal relations between development of motor symptoms and GI dysfunction. This work will provide key locations in the CNS and ENS at which to target therapy and determine whether enteric neuroprotection is a viable therapeutic for PD.


Parkinson's disease and the gut: a well known clinical association in need of an effective cure and explanation.

Abstract: Parkinson's disease (PD) is a neurodegenerative disorder which leads to severe movement impairment; however, Parkinsonian patients frequently suffer from gastrointestinal (GI) problems which at present are poorly understood, scarcely investigated, and lack an effective cure. Traditionally, PD is attributed to the loss of mesencephalic dopamine-containing neurons; nonetheless, additional nuclei, such as the dorsal motor nucleus of the vagus nerve and specific central noradrenergic nuclei, are now identified as targets of PD. While the effects of PD on the somatic motor systems are well characterized, the influence on the digestive system still needs to be clarified. Recent findings demonstrate the occurrence of pathological alterations within peripheral neuronal networks in the GI tract of Parkinsonian patients. However, it remains unclear whether a real cell loss occurs, and whether this happens specifically for a subclass of autonomic neurons or if it reflects the sole loss of autonomic nerves. This review summarizes the neurochemical and morphological changes which might be responsible for impaired GI motility. Moreover, we focus on the experimental models to reproduce the altered digestive system of Parkinsonian patients since an experimental model able to mimic such features of PD is required. In the last part of the manuscript, we suggest potential therapeutic targets.

Pub.: 19 Jun '08, Pinned: 21 Mar '18