Noradrenergic loss enhances MDMA toxicity and induces ubiquitin-positive striatal whorls.
Movement disorders involve a number of neurodegenerative conditions, mostly affecting basal ganglia. Parkinson's disease (PD) is classically defined by the selective loss of dopaminergic neurons in the substantia nigra pars compacta. Administration of specific neurotoxins represents a common tool to reproduce this lesion. Among these, amphetamine derivatives act as powerful monoamine neurotoxins, impairing striatal dopamine (DA) axons in mice. Despite the well-investigated effects on striatal DA terminals, only sporadic studies have focused on the potential toxicity of amphetamines towards post-synaptic neurons within the striatum. In the present work we found that 3,4-methylenedioxymethamphetamine (MDMA) produces ultrastructural alterations in striatal cells, featuring as membraneous whorls, positive for ubiquitin and heat shock protein 70. These morphological alterations were enhanced in locus coeruleus-lesioned mice.
Ferrucci
M
M
Department of Human Morphology and Applied Biology, University of Pisa, Via Roma 55, I-56126 Pisa, Italy.
Gesi
M
M
Lenzi
P
P
Soldani
P
P
Ruffoli
R
R
Pellegrini
A
A
Ruggieri
S
S
Paparelli
A
A
Fornai
F
F
D018759:Adrenergic Uptake Inhibitors / Q000633:toxicity*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D008125:Locus Coeruleus / Q000601:surgery; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009474:Neurons / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D009638:Norepinephrine / Q000172:deficiency*; D025801:Ubiquitin / Q000378:metabolism*; D014463:Ultrasonography
D018759:Adrenergic Uptake Inhibitors; D018840:HSP70 Heat-Shock Proteins; D025801:Ubiquitin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009638:Norepinephrine