Enhanced sensitivity of dopaminergic neurons to rotenone-induced toxicity with aging.
Rotenone has been reported to induce various degrees of Parkinsonism in rats. We tested whether advancing age alters the sensitivity of dopaminergic neurons to rotenone. A low, systemic dose of rotenone had no effect on young rats, but led to a 20-30% reduction of tyrosine hydroxylase-positive neurons in the substantia nigra of older rats. The effect was specific to nigral dopaminergic neurons and may be associated with the increase of glial cell activation in older rats. These data suggest that age enhances the sensitivity of dopaminergic neurons to rotenone and should be considered when assessing models of Parkinson's disease.
Phinney
Amie L
AL
Department of Medical Pharmacology, Institute for Clinical and Experimental Neurosciences, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Andringa
Gerda
G
Bol
John G J M
JG
Wolters
Erik Ch
ECh
van Muiswinkel
Freek L
FL
van Dam
Anne-Marie W
AM
Drukarch
Benjamin
B
D000375:Aging / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D002452:Cell Count; D004298:Dopamine / Q000502:physiology*; D007150:Immunohistochemistry; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D017628:Microglia / Q000187:drug effects; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D012402:Rotenone / Q000633:toxicity*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
D007306:Insecticides; D018377:Neurotransmitter Agents; D051844:alpha-Synuclein; D012402:Rotenone; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine