Behavioural and neural deficits induced by rotenone in the pond snail Lymnaea stagnalis. A possible model for Parkinson's disease in an invertebrate.
Parkinson's disease is a neurodegenerative disorder, related to the loss of dopamine (DA)-containing neurons in the substantia nigra. In experimental animals, both vertebrates and invertebrates, rotenone, a commercially available organic pesticide, induces symptoms of Parkinson's disease. We found that that rotenone is toxic to the pond snail Lymnaea stagnalis (4-day LC50 0.8 microM). Rotenone, at concentrations from 0.1 to 5 microM, caused progressive and irreversible behavioural deficits in both acute and chronic exposure. Chronic exposure to 0.5 microM rotenone led to a progressive decrease in spontaneous locomotion and in feeding, reaching almost 100% inhibition of both behaviours by the 7th day of rotenone treatment. In the central nervous system preparation made on the 7th day of treatment the postsynaptic potentials evoked by the identified dopaminergic RPeD1 neuron disappeared whereas the synaptic inputs received by the RPeD1 from a peptidergic neuron (VD4) were still functional. Immunostaining revealed that the tyrosine hydroxylase immunoreactivity decreased below the detectable level in both the RPeD1 cell body and its axonal processes. Finally, HPLC assay showed a significant (25%) decrease in DA level in the CNS by the 7th day of rotenone treatment. We conclude that, as in vertebrates, rotenone disrupts feeding and locomotion of the model mollusc Lymnaea stagnalis. One possible target of rotenone is the dopaminergic neurons in the CNS. We therefore suggest that Lymnaea stagnalis is a suitable invertebrate model for the study of Parkinson's disease, allowing direct analysis of the response of dopaminergic systems to rotenone at behavioural, cellular and neuronal levels.
Vehovszky
Agnes
A
Balaton Limnological Research Institute, Hungarian Academy of Sciences, Department of Experimental Zoology, Tihany, PO Box 35, Hungary H-8237. agnes@tres.blki.hu
Szabó
Henriette
H
Hiripi
László
L
Elliott
Christopher J H
CJ
Hernádi
László
L
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002490:Central Nervous System / Q000033:anatomy & histology / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004594:Electrophysiology; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D008195:Lymnaea / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010300:Parkinson Disease / Q000503:physiopathology*; D012402:Rotenone / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D007306:Insecticides; D012402:Rotenone; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine