Animal models of Parkinson’s disease progression

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology is not understood. This disease occurs both sporadically and through inheritance of single genes, although the familial types are rare. Over the past decade or so, experimental and clinical data suggest that PD could be a multifactorial, neurodegenerative disease that involves strong interactions between the environment and genetic predisposition. Our understanding of the pathophysiology and motor deficits of the disease relies heavily on fundamental research on animal models and the last few years have seen an explosion of toxin-, inflammation-induced and genetically manipulated models. The insight gained from the use of such models has strongly advanced our understanding of the progression and stages of the disease. The models have also aided the development of novel therapies to improve symptomatic management, and they are critical for the development of neuroprotective strategies. This review critically evaluates these in vivo models and the roles they play in mimicking the progression of PD.

β-arrestin protects neurons by mediating endogenous opioid arrest of inflammatory microglia

“…Second, as SN DA neurons are especially vulnerable to inflammatory insult, presumably because of the higher density of microglia in the SN than in other regions, 41 intracerebral injections of LPS into the SN of mice have proven a well-established animal model to study acute inflammation-induced DA neurodegeneration. 29,42 Supporting these contentions, we detected significant neuronal death only in the neurons cocultured with LPS-treated microglia instead of in the neurons directly treated with LPS (Supplementary Figure S1b). Neuronal death was further enhanced in neurons cultured with the CM from LPS-treated microglia (or from LPS-treated microglia plus astrocytes) derived from Kor À / À mice.…”

“…[8][9][10] Thus, the activation of microglia by an intracerebral injection of an endotoxin such as lipopolysaccharide (LPS) is sufficient to cause the loss of TH þ neurons. 11 However, it has remained elusive how microglial activity is regulated.…”

Acute versus long-term effects of 6-hydroxydopamine on oxidative stress and dopamine depletion in the striatum of mice

“…The currently described methodology might help to distinguish between the several parameters contributing to the hydroxyl radical formation and to further investigate for example the role of microglial activation and the intraneuronal uptake by the DA transporter in oxidative stress. Furthermore, next to toxininduced animal models of Parkinsonism, recent advances in genetic approaches significantly extended the variety of animal models by introducing mouse strains carrying specific genetic alterations (Meredith et al, 2008;Sotnikova and Gainetdinov, 2007).…”

“…Even though the precise etiology of Parkinson's disease remains uncertain, genetic and/or environmental factors are clearly important in its pathogenesis (Aoyama et al, 2008;Meredith et al, 2008;Obeso et al, 2010;Przedborski, 2005) among which oxidative stress (Koutsilieri et al, 2002;Yacoubian and Standaert, 2009) is one of the most commonly accepted mechanisms (Aoyama et al, 2008;Garcia et al, 2000;Jenner, 2003;Schulz et al, 2000). Oxidative stress can be described as a condition in…”

Effect of silybin in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) induced parkinsonism in mice

“…24 The murine MPTP model constitutes the best characterized toxin paradigm for PD, faithfully replicating most of its clinical and pathological hallmarks. 25 Various studies had been done to assess the time course of MPTP induced cell death in mice and have proved that greatest loss of dopaminergic neurons was observed at 7 days. 26 Hence in the present study also swiss male albino mice were used and they were subjected to behavioral, biochemical and histopathological analysis at 7 days after last MPTP dosing.…”