Animal models of Parkinson's disease in rodents induced by toxins: an update.
The development of animal models of Parkinson's disease is of great importance in order to test substitutive or neuroprotective strategies for Parkinson's disease. Such models should reproduce the main characteristics of the disease, such as a selective lesion of dopaminergic neurons that evolves over time and the presence of neuronal inclusions known as Lewy bodies. Optimally, such models should also reproduce the lesion of non-dopaminergic neurons observed in a great majority of patients with Parkinson's disease. From a behavioral point of view, a parkinsonian syndrome should be observed, ideally with akinesia, rigidity and rest tremor. These symptoms should be alleviated by dopamine replacement therapy, which may in turn lead to side effects such as dyskinesia. In this review, we analyze the main characteristics of experimental models of Parkinson's disease induced by neurotoxic compounds such as 6-hydroxydopamine, MPTP and rotenone. We show that, whereas MPTP and 6-hydroxydopamine induce a selective loss of catecholaminergic neurons that in most cases evolves over a short period of time, rotenone infusion by osmotic pumps can induce a chronically progressive degeneration of dopaminergic neurons and also of non-dopaminergic neurons in both the basal ganglia and the brainstem.
Hirsch
E C
EC
INSERM U289, Experimental Neurology and Therapeutics, Hôpital de la Salpêtrière, Paris, France.
Höglinger
G
G
Rousselet
E
E
Breidert
T
T
Parain
K
K
Feger
J
J
Ruberg
M
M
Prigent
A
A
Cohen-Salmon
C
C
Launay
J M
JM
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D018663:Adrenergic Agents; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents; D009410:Nerve Degeneration / Q000139:chemically induced*; D009474:Neurons / Q000187:drug effects*; D016627:Oxidopamine; D010300:Parkinson Disease; D012377:Rodentia; D012402:Rotenone; D014475:Uncoupling Agents
D018663:Adrenergic Agents; D015259:Dopamine Agents; D014475:Uncoupling Agents; D012402:Rotenone; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine