Parkinson's Disease

Parkinson’s disease (PD) is a neurodegenerative disease characterized by motor symptoms, but also including various non-motor disturbances, in particular frequent gastrointestinal (GI) dysfunction — namely constipation and delayed gastric emptying — that predate the onset of motor symptoms such as bradykinesia, rigidity, tremor and postural instability. Constipation is one of the most prevalent non-motor symptoms of PD and it has been identified as a predictor of developing PD in a retrospective study. Dr. Lixin Wang investigates the alterations of gut motor functions in different experimental models of Parkinson’s disease and whether the prokinetic hormone ghrelin, through its prokinetic, orexigenic and anti-inflammatory actions, may have beneficial effects.

Approach

  • Genetic mouse model of Parkinson overexpressing α-synclein
  • Chemical rat model of Parkinson with 6-hydroxydopamine injection into medial forebrain bundle
  • Monitoring food and water intake
  • Gastric transit
  • Colonic propulsive motor function
  • Brain activation using Fos immunohistochemistry
  • Myenteric ganglion ganglia assessment in whole mount and immunohistochemical labeling
  • Circulating ghrelin

Grants

  • VA Rehab Grant. Ghrelin Agonists Multiple Beneficial Effects on Parkinson’s Non-motor Symptoms. L. Wang, PI, Y. Taché, Co-Investigator. 06/01/2015-05/31/2019
  • NIH DK-41301 Digestive Diseases Center Grant, Animal Core. Y. Taché, Director, M. Million, Associate Director, L. Wang, Co-Investigator. 11/01/2014-10/31/2019

Publications

  1. Karasawa H, Pietra C, Giuliano C, Garcia-Rubio S, Xu X, Yakabi S, Taché Y, Wang L. New ghrelin agonist, HM01 alleviates constipation and L-dopa-delayed gastric emptying in 6-hydroxydopamine rat model of Parkinson's diseaseNeurogastroenterol Motil. 2014 Dec;26(12):1771-82
  2. Wang L, Mogami S, Karasawa H, Yamada C, Yakabi S, Yakabi K, Hattori T, Taché Y. Preventive effect of rikkunshito on gastric motor function inhibited by L-dopa in ratsPeptides. 2014 May;55:136-44
  3. Wang L, Magen I, Yuan PQ, Subramaniam SR, Richter F, Chesselet MF, Taché Y. Mice overexpressing wild-type human alpha-synuclein display alterations in colonic myenteric ganglia and defecationNeurogastroenterol Motil. 2012 Sep;24(9):e425-36
  4. Wang L, Fleming SM, Chesselet MF, Taché Y. Abnormal colonic motility in mice overexpressing human wild-type alpha-synucleinNeuroreport. 2008 May 28;19(8):873-6