Rotenone induces non-specific central nervous system and systemic toxicity.
We investigated the dopaminergic (DA) neuronal degeneration in animals subjected to systemic treatment of rotenone via subcutaneous delivery. Behavioral observations revealed a hypokinetic period in rats sacrificed at 3 and 5 days, and dystonic episodes in animals sacrificed at 8 days. Less than 20% of the total number of animals given rotenone depicted brain lesions after 8 days of treatment, as demonstrated by a significant loss of DA fibers in the striatum, but not of DA nigral neurons. Tyrosine hydroxylase-negative striatal territories were characterized by post-synaptic toxicity as demonstrated by a decreased number of interneurons labeled for choline acetyltransferase, NADPH-diaphorase, parvalbumin, and projection neurons labeled for calbindin and nerve growth factor inducible-B (NGFI-B). Post-synaptic neurodegeneration was demonstrated further by abundant striatal staining for Fluoro-Jade. Decrease in the nuclear orphan receptor Nurr1 expression was the only significant change observed at the level of the substantia nigra. Autopsy reports confirmed that animals suffered from severe digestion problems. These data suggest that hypokinesia observed between 3 and 5 days is the result of general health problems rather than a specific motor deficit associated to Parkinson's disease (PD) symptoms. Overall, the effects of rotenone toxicity are widespread, and subcutaneous administration of this toxin does not provide the neuropathological and behavioral basis for a relevant and reliable PD model.
Lapointe
Nicolas
N
Centre de Recherche en Neurosciences, CHUL, Sainte-Foy, Québec, Canada.
St-Hilaire
Michel
M
Martinoli
Maria-Grazia
MG
Blanchet
Julie
J
Gould
Peter
P
Rouillard
Claude
C
Cicchetti
Francesca
F
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D051381:Rats; D012402:Rotenone / Q000633:toxicity*
D012402:Rotenone; D004298:Dopamine