Parkinson's disease-like syndrome in rats induced by 2,9-dimethyl-beta-carbolinium ion, a beta-carboline occurring in the human brain.
Regarding the pathogenesis of Parkinson's disease, a neurotoxin hypothesis was proposed following the discovery that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a Parkinson-like syndrome in humans and primates. Since then, researchers have searched for endogenous and exogenous compounds that are structurally similar to this neurotoxin. Such compounds include beta-carbolines, formed from tryptophan and its derivatives. beta-carbolines are present naturally in the human brain and cerebrospinal fluid. The present study examined the effect of bilateral, intranigral administration of 2,9-dimethyl-beta-carbolinium ion on muscle tone, electromyographic activity, dopamine metabolism in the striatum, and the number of tyrosine hydroxylase-immunoreactive neurons and volume of the substantia nigra in rats. We found that the beta-carbolinium ion (15 or 40 nmol per side) caused a significant decrease in the striatal levels of dopamine and its metabolites, which was accompanied by an enhancement of muscle tone and electromyographic activity. Stereological counting revealed that the beta-carbolinium caused a significant decrease in the total number of tyrosine hydroxylase-immunoreactive neurons and shrinkage of the substantia nigra. The findings suggest that the methylated beta-carbolinium ion produces a dose-dependent degeneration of nigrostriatal neurons, leading to deficits in dopaminergic neurotransmission and an increase of muscle resistance and electromyographic activity, a syndrome equivalent to muscle rigidity in Parkinson's disease.
Lorenc-Koci
Elzbieta
E
Department of aNeuropsychopharmacology, Institute of Pharmacology, Polish Academy of Science, Kraków, Poland.
Rommelspacher
Hans
H
Schulze
Gert
G
Wernicke
Catrin
C
Kuter
Katarzyna
K
Smiałowska
Maria
M
Wierońska
Joana
J
Zieba
Barbara
B
Ossowska
Krystyna
K
D000818:Animals; D002243:Carbolines / Q000032:analysis / Q000633:toxicity*; D002452:Cell Count; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects; D004292:Dominance, Cerebral; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004576:Electromyography / Q000187:drug effects; D006801:Humans; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009434:Neural Pathways / Q000737:chemistry / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D009498:Neurotoxins / Q000032:analysis / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000737:chemistry* / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D002243:Carbolines; D009498:Neurotoxins; C005986:2,9-dimethyl-beta-carbolinium; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine