Overview of Mouse Models of Parkinson's Disease

Abstract

Parkinson's disease is a neurodegenerative disorder characterized by the loss of neurons in specific regions of the nervous system, notably in the substantia nigra pars compacta and, in most cases, by the deposition of intraneuronal inclusions named Lewy bodies. These pathological alterations have profound effects on the brain function, leading to the progressive development of various symptoms, the most prominent being the impaired initiation of voluntary movements caused by the loss of dopamine signaling in the basal ganglia. Here, we provide an overview of the mouse models of Parkinson's disease, with the goal of guiding selection of the most appropriate model for studying the question at hand. Pharmacological approaches targeting dopamine signaling and toxins leading to selective degeneration of nigral neurons are used to validate symptomatic treatments that aim at restoring effective dopaminergic function for motor control. Alternative mouse models are based on genetic modifications that are meant to reproduce the inherited alterations associated with familial forms of Parkinson's disease. Although genetic models have most often failed to induce overt degeneration of nigral dopaminergic neurons, they provide essential tools to explore the multifactorial etiology of this complex neurodegenerative disorder.

A novel dual GLP-1 and GIP receptor agonist is neuroprotective in the MPTP mouse model of Parkinson′s disease by increasing expression of BNDF

“…However, the MPTP toxin induced animal model of PD has its limitations. The dual analogues will have to be tested in other animal models of PD that use different chemicals to induce PD-like symptoms such as 6-OHDA or LPS injection into the brain (Bertilsson et al, 2008;Harkavyi et al, 2008), and in transgenic mouse models that express human mutated genes that are known to induce Parkinson's disease (Bobela et al, 2014;Giraldez-Perez et al, 2014).…”

Neuroprotective effects of (Val8)GLP-1-Glu-PAL in the MPTP Parkinson’s disease mouse model

“…However, Val(8)GLP--1(glu--PAL) will have to be tested in other animal models of PD that use different chemicals to induce PD--like symptoms such as 6--OHDA or LPS injection into the brain (Bertilsson et al, 2008;Harkavyi et al, 2008), and in transgenic mouse models that express human mutated genes that are known to induce Parkinson's disease (Bobela, Zheng, & Schneider, 2014;Giraldez--Perez, Antolin--Vallespin, Munoz, & Sanchez--Capelo, 2014). Another important test to be conducted is to treat animals after inducing the PD lesion in order to assess the regenerative effect of the novel drugs.…”

Immune Signaling in Neurodegeneration

“…Transgenic overexpression of familial mutations of the human a-synuclein gene in mice can cause toxic fibril buildup and Lewy body formation, but does not specifically target dopaminergic neurons and leads to widespread neuronal pathology outside nigrostriatal circuits (Visanji et al, 2016). Other PD models including mutations in other genetic risk factors and seeding of a-synuclein have been useful for teasing apart other mechanisms of disease pathogenesis and have been reviewed in detail elsewhere (Bobela et al, 2014;Lee et al, 2012;Tieu, 2011;Visanji et al, 2016).…”