Gait and bowel movement analysis - early diagnosis of neurodegenerative diseases via motility analysis of the bowel

Motor changes are one of the cardinal symptoms in patients with Parkinson's disease. Both gait, fine motor skills and facial expressions are significantly impaired. However, this is only the case when a large proportion of the affected nerve cells in the basal ganglia of the brain have already died. This also means that it is too late for a causal therapy. Interestingly, many Parkinson's patients show gastrointestinal symptoms long before their motor skills are impaired or the disease can be diagnosed with certainty. It is therefore likely that the gastrointestinal tract is affected in these patients long before other symptoms appear. In fact, so-called Lewi bodies, aggregates of the pathological peptide synuclein1, have been found in nerve cells of the intestine in intestinal biopsies of Parkinson's patients. In principle, the microbiome and markers for the quality of the mucosal barrier are altered in Parkinson's patients2,3. In a mouse model of Parkinson's disease, young and old mice were subjected to a movement analysis on a "cat walk". The mice walk on an illuminated glass plate so that the footprints can be automatically recorded and analyzed. Step length, speed and a whole range of other parameters can be recorded. These tests showed a clear slowdown in most parameters in the old sick animals, while no significant changes were seen in the 2-month-old animals. In the younger animals, both small and large intestines were removed and 3 cm long intestinal segments were perfused in an organ bath4. The intestine continues to move autonomously in the organ bath and the movement can be continuously recorded via a video recorder. A virtual frame can be placed over relevant sections of the intestine and an upper and lower virtual row of dots can be created. The rows of dots mark the light-dark contrast and are recorded over the measurement period. The difference between the upper and lower rows of dots is used to determine the respective intestinal diameters with spatial and temporal resolution. The data is color-coded from oral to aboral. The darker the color, the stronger the contraction. The frequency and speed of contraction propagation can also be determined mathematically. All these values are strongly altered in Parkinson's mice (psA30P).

Bibliography (APA):

1: Braak, H., De Vos, R. A. I., Bohl, J. & Del Tredici, K. Gastric α-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease- related brain pathology. Neurosci. Lett. (2006) doi:10.1016/j.neulet.2005.11.012.

2:Unger MM, Spiegel J, Dillmann KU, Grundmann D, Philippeit H, Bürmann J, Faßbender K, Schwiertz A, Schäfer KH. Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls. Parkinsonism Relat Disord. 2016 Aug 26. pii: S1353-8020(16)30323-6. doi: 10.1016/j.parkreldis.2016.08.019. PMID: 27591074

3: Schwiertz A, Spiegel J, Dillmann U, Grundmann D, Bürmann J, Faßbender K, Schäfer KH, Unger MM.Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson's disease. Parkinsonism Relat Disord. 2018 May;50:104-107. doi: 10.1016/j.parkreldis.2018.02.022.

4: Schreiber D, Jost V, Bischof M, Seebach K, Lammers WJ, Douglas R, Schäfer KH. Motility patterns of ex vivo intestine segments depend on perfusion mode. World J Gastroenterol. 2014 Dec 28;20(48):18216-27. doi: 10.3748/wjg.v20.i48.18216.