Abnormal colonic motility in mice overexpressing human wild-type alpha-synuclein.
The presynaptic protein alpha-synuclein (alphaSyn) has been implicated in both familial and sporadic forms of Parkinson's disease. We examined whether human alphaSyn-overexpressing mice under Thy1 promoter (Thy1-alphaSyn) display alterations of colonic function. Basal fecal output was decreased in Thy1-alphaSyn mice fed ad libitum. Fasted/refed Thy1-alphaSyn mice had a slower distal colonic transit than the wild-type mice, as monitored by 2.2-fold increase in time to expel an intracolonic bead and 2.9-fold higher colonic fecal content. By contrast, Thy1-alphaSyn mice had an increased fecal response to novelty stress and corticotropin releasing factor injected intraperipherally. These results indicate that Thy1-alphaSyn mice display altered basal and stress-stimulated propulsive colonic motility and will be a useful model to study gut dysfunction associated with Parkinson's disease.
Wang
Lixin
L
CURE/Digestive Diseases Center and Center for Neurobiology of Stress, David Geffen School of Medicine, University of California at Los Angeles and VAGLAHS, Los Angeles, California, USA. lixinw@ucla.edu
Fleming
Sheila M
SM
Chesselet
Marie-Françoise
MF
Taché
Yvette
Y
D000818:Animals; D003106:Colon / Q000502:physiology*; D003248:Constipation / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D004195:Disease Models, Animal; D005243:Feces; D005769:Gastrointestinal Motility / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D018800:Thy-1 Antigens / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics / Q000502:physiology*
D018800:Thy-1 Antigens; D051844:alpha-Synuclein; D003346:Corticotropin-Releasing Hormone