Animal models of Parkinson’s disease in rodents induced by toxins: an update

Abstract

Summary. 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.

TRPC1-mediated Inhibition of 1-Methyl-4-phenylpyridinium Ion Neurotoxicity in Human SH-SY5Y Neuroblastoma Cells

“…ϩ is a metabolic product of MPTP and is known to induce cell death in dopaminergic neurons (1,3). To demonstrate the specific role of TRPC1, we transformed SH-SY5Y cells with either antisense TRPC1 constructs or overexpressed TRPC1 using adenoviral constructs.…”

“…Parkinson's disease is a progressive neurodegenerative disorder associated with selective loss of the dopaminergic neurons in the substantia nigra pars compacta (1). Neurotoxins, such as 1-methyl-4-phenylpyridinium ion (MPP ϩ ), 1 cause selective nigral dopaminergic lesions and cause Parkinsonian syndrome (2)(3)(4)(5).…”

“…Neurotoxins, such as 1-methyl-4-phenylpyridinium ion (MPP ϩ ), 1 cause selective nigral dopaminergic lesions and cause Parkinsonian syndrome (2)(3)(4)(5). Although the underlying cause of dopaminergic cell death or the molecular mechanism by which these cells degenerate is still not fully understood, several molecular mechanisms have been proposed to play a role that includes overproduction of reactive oxygen species, impairment of mitochondrial respiration, disturbances of Ca 2ϩ homeostasis, and excitotoxicity (6 -10).…”

Pharmacological inhibition of neuronal NADPH oxidase protects against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress and apoptosis in mesencephalic dopaminergic neuronal cells

“…Recent studies have demonstrated oxidative stress as the major initiator of apoptotic cell death in several neurodegenerative disorders, including PD (Zigmond et al, 2002;Dawson and Dawson, 2003;Di Monte, 2003;Jenner, 2003;Kanthasamy et al, 2003;Thiruchelvam et al, 2003;Greenamyre and Hastings, 2004;Maguire-Zeiss et al, 2005;Przedborski and Ischiropoulos, 2005;McCormack et al, 2006). The potent dopaminergic toxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydro--pyridine) causes an irreversible PD-like syndrome in humans, non-human primates, and in animals, and reproduces most of the neurochemical and pathological hallmarks, including the substantial degeneration of dopaminergic neurons; consequently, MPTP has been used extensively in experimental PD models (Dauer and Przedborski, 2003;Hirsch et al, 2003b;Przedborski et al, 2004;Bove et al, 2005;Smeyne and Jackson-Lewis, 2005;Watanabe et al, 2005).…”

Ligands of Receptor for Advanced Glycation End-Products Produced by Activated Microglia are Critical in Neurodegenerative Diseases

“…Although the cause of AD progression is unclear, AD is characterized by inflammatory responses to amyloid-β (Aβ), microglia activation, and astrocyte recruitment by Aβ deposits [7]. Parkinson's disease (PD) is occurs by loss of dopaminergic neurons in the substantia nigra (SN) and by many other events and agents, such as, genetic events or toxic drugs or chemicals, such as, 1-methyl-4-phenyl-1,2,3-6 tetrahydropyridine or rotenone [8,9]. Pathologic changes in the PD brain are closely related to microglial activation induced inflammation, which accelerates dopamine (DA)-producing neuron death.…”