title: Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol.
abstract: BACKGROUND
  Impairment of the enteric nervous system has been suggested to occur within the pathogenesis of neurodegenerative diseases. Thus, in the current study, we consider salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, SAL) as a substance that can potentially induce myenteric neurodegen-eration.
  
  
  METHODS
  Male Wistar rats were subjected to continuous intraperitoneal dosing of salsolinol (200 mg/kg in total) with osmotic mini-pumps for either two or four weeks. An equivalent group of rats served as the control. Jejunal myenteric neurons were subjected to immunofluorescence staining to detect neuron specific protein - protein gene product (pan-neuronal marker, PGP 9.5), nitric oxide synthase (NOS), choline acetyltransferase (ChAT), Bax-protein and alpha-synuclein. In search of any functional impairment within the gastrointestinal tract, gut motility was assessed by determining the residual solid food contents in the stomach and the small and large intestine transit.
  
  
  RESULTS
  The myenteric neuron count, the mean size of the neuron body, the area of ganglia and the diameter of nerve strands were decreased in both of the salsolinol-treated groups compared with the controls. The number of NOS-positive cells was lower in the salsolinol-treated groups, while the number of ChAT-positive cells remained unchanged in comparison with the controls. Neurons expressing the pro-apoptotic Bax protein and alpha-synuclein deposits were observed among the myenteric neurons of the salsolinol-treated rats.
  
  
  CONCLUSIONS
  Salsolinol evokes enteric neuronal cell death via initiation of apoptosis and leads to the formation of pathological aggregates of alpha-synuclein. Impairment of myenteric neurons, mainly the inhibitory motor neurons, might be responsible for the abnormal intestinal transit. Thus, salsolinol might be regarded as a suitable compound for inducing experimental enteric neurodegeneration in rats.
authors: Department of Pathophysiology, Jagiellonian University Medical College, Krakow, Poland. magdalena.kurnik@uj.edu.pl.
authors: Magdalena
authors: M
authors: Kurnik
authors: Krzysztof
authors: K
authors: Gil
authors: Mariusz
authors: M
authors: Gajda
authors: Piotr
authors: P
authors: Thor
authors: Andrzej
authors: A
authors: Bugajski
mesh_terms: D000818:Animals; D017209:Apoptosis; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007418:Intestinal Pseudo-Obstruction / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D007546:Isoquinolines / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D007546:Isoquinolines; D051844:alpha-Synuclein; D051028:bcl-2-Associated X Protein; C036617:salsolinol; D019001:Nitric Oxide Synthase; D002795:Choline O-Acetyltransferase; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase