Kinetics of microglial activation and degeneration of dopamine-containing neurons in a rat model of Parkinson disease induced by 6-hydroxydopamine.
In both Parkinson disease and in animal models of Parkinson disease, there is a microglial reaction in addition to the loss of dopaminergic neurons in the ventral midbrain. To determine the pathological role of this microglial reaction, we analyzed the kinetics of microglial activation and dopaminergic cell death induced in rats with the neurotoxin 6-hydroxydopamine. As early as Day 1 after the injection, there was a decline in the motor performance of the 6-hydroxydopamine-lesioned rats that correlated with a reduction of dopaminergic innervation of the contralateral striatum. Loss of dopaminergic neurons in the ventral midbrain developed a few days later and seemed to follow a specific temporospatial pattern. Degenerating neurons and activated microglia were seen only in areas in which dopaminergic cells were no longer observed, suggesting that the loss of the dopaminergic phenotype preceded the degenerative process. In sham-lesioned rats, there was a transient activation of microglia in the vicinity of the needle tract without any cell degeneration. This chronology of events supports the hypothesis that microglial activation is a secondary rather than primary phenomenon in dopaminergic cell degeneration induced by 6-hydroxydopamine.
Henry
Vincent
V
Institut National de la Santé et de la Recherche Médicale, UMR 643,CHU de Nantes, Nantes Cedex 01, France.
Paillé
Vincent
V
Lelan
Faustine
F
Brachet
Philippe
P
Damier
Philippe
P
D000818:Animals; D016923:Cell Death / Q000502:physiology; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008636:Mesencephalon / Q000473:pathology / Q000503:physiopathology; D017628:Microglia / Q000473:pathology / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D016627:Oxidopamine; D004298:Dopamine