Animal models of the non-motor features of Parkinson's disease

McDowell, Kimberly A.; Chesselet, Marie‐Françoise

doi:10.1016/j.nbd.2011.12.040

Cited by 141 publications

(101 citation statements)

References 171 publications

(185 reference statements)

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“…Some of these nonmotor symptoms are improved by dopaminergic therapy, but most are not, and their presence many years before the onset of the dopamine-responsive neurological symptoms suggests that they may be due to the dysfunction of other neuronal systems. This would explain that they are not always reproduced in models based on toxin-induced selective dopaminergic cell loss [48]. Indeed, extensive extra-nigral alphasynuclein pathology is detected in PD brains and may be present even before the onset of motor symptoms [3].…”

Section: Loss Of Striatal Dopamine Is Preceded By Increased Extracellmentioning

confidence: 99%

A Progressive Mouse Model of Parkinson's Disease: The Thy1-aSyn (“Line 61”) Mice

et al. 2012

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Identification of mutations that cause rare familial forms of Parkinson's disease (PD) and subsequent studies of genetic risk factors for sporadic PD have led to an improved understanding of the pathological mechanisms that may cause nonfamilial PD. In particular, genetic and pathological studies strongly suggest that alpha-synuclein, albeit very rarely mutated in PD patients, plays a critical role in the vast majority of individuals with the sporadic form of the disease. We have extensively characterized a mouse model over-expressing full-length, human, wild-type alpha-synuclein under the Thy-1 promoter. We have also shown that this model reproduces many features of sporadic PD, including progressive changes in dopamine release and striatal content, alphasynuclein pathology, deficits in motor and nonmotor functions that are affected in pre-manifest and manifest phases of PD, inflammation, and biochemical and molecular changes similar to those observed in PD. Preclinical studies have already demonstrated improvement with promising new drugs in this model, which provides an opportunity to test novel neuroprotective strategies during different phases of the disorder using endpoint measures with high power to detect drug effects.

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Section: Loss Of Striatal Dopamine Is Preceded By Increased Extracellmentioning

confidence: 99%

A Progressive Mouse Model of Parkinson's Disease: The Thy1-aSyn (“Line 61”) Mice

et al. 2012

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“…Different toxins, such as 6-OHDA (6-hydroksydopamine), MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), paraquat, maneb and rotenone (three commonly used pesticides), are often used to generate enteric Parkinsonian-like neuronal degeneration [12][13][14][15][16]. Morphological and quantitative alternations (especially the presence of pathological alpha-synuclein aggregates) in the ENS neurons, together with gut dysmotility, malabsorption and disrupted excretion, have been observed after the animals were subjected to those different neurotoxins.…”

Section: Introductionmentioning

confidence: 99%

Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol

Kurnik

Gil

Gajda

et al. 2015

Folia Histochem Cytobiol.

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Introduction. Impairment of the enteric nervous system has been suggested to occur within the pathogenesis of neurodegenerative diseases. Thus, in the current study, we consider salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, SAL) as a substance that can potentially induce myenteric neurodegeneration. Material and methods. Male Wistar rats were subjected to continuous intraperitoneal dosing of salsolinol (200 mg/kg in total) with osmotic mini-pumps for either two or four weeks. An equivalent group of rats served as the control. Jejunal myenteric neurons were subjected to immunofluorescence staining to detect neuron specific protein -protein gene product (pan-neuronal marker, PGP 9.5), nitric oxide synthase (NOS), choline acetyltransferase (ChAT), Bax-protein and alpha-synuclein. In search of any functional impairment within the gastrointestinal tract, gut motility was assessed by determining the residual solid food contents in the stomach and the small and large intestine transit. Results. The myenteric neuron count, the mean size of the neuron body, the area of ganglia and the diameter of nerve strands were decreased in both of the salsolinol-treated groups compared with the controls. The number of NOS-positive cells was lower in the salsolinol-treated groups, while the number of ChAT-positive cells remained unchanged in comparison with the controls. Neurons expressing the pro-apoptotic Bax protein and alpha-synuclein deposits were observed among the myenteric neurons of the salsolinol-treated rats. Conclusions. Salsolinol evokes enteric neuronal cell death via initiation of apoptosis and leads to the formation of pathological aggregates of alpha-synuclein. Impairment of myenteric neurons, mainly the inhibitory motor neurons, might be responsible for the abnormal intestinal transit. Thus, salsolinol might be regarded as a suitable compound for inducing experimental enteric neurodegeneration in rats.

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“…MPTP is also used to study certain non-motor features of PD [14]. For example, in a marmoset monkey model, MPTP administration manifests conspicuous sleep changes resembling RBD [29].…”

Section: -Hydroxydopamine-lesioned Modelmentioning

confidence: 99%

“…There are basically 2 broad categories of animal models used to study mechanisms and treatment of PD: the neurotoxic models and the genetic models that utilize the in vivo manipulation of PD-related genes [12][13][14]. Several other models have been also developed to explore the role of UPS and inflammatory or immune effects.…”

Section: Introductionmentioning

confidence: 99%

“…However, transgenic or knockout genetic models may better simulate the pathogenic mechanisms of genetic forms of PD, but their pathological and behavioral phenotype is often quite different from the human condition [13]. Other models may be required to study the non-motor aspects of PD [14]. Therefore, the selection of a particular animal model largely depends on the specific objectives and goals of the experiments.…”

Section: Introductionmentioning

confidence: 99%

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Animal Models of Parkinson's Disease: A Gateway to Therapeutics?

Sayana

Jankovic

2014

Neurotherapeutics

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Parkinson's disease (PD) is a progressive, neurodegenerative disorder of unknown etiology, although a complex interaction between environmental and genetic factors has been implicated as a pathogenic mechanism of selected neuronal loss. A better understanding of the etiology, pathogenesis, and molecular mechanisms underlying the disease process may be gained from research on animal models. While cell and tissue models are helpful in unraveling involved molecular pathways, animal models are much better suited to study the pathogenesis and potential treatment strategies. The animal models most relevant to PD include those generated by neurotoxic chemicals that selectively disrupt the catecholaminergic system such as 6-hydroxydopamine; 1-methyl-1,2,3,6-tetrahydropiridine; agricultural pesticide toxins, such as rotenone and paraquat; the ubiquitin proteasome system inhibitors; inflammatory modulators; and several genetically manipulated models, such as α-synuclein, DJ-1, PINK1, Parkin, and leucine-rich repeat kinase 2 transgenic or knock-out animals. Genetic and nongenetic animal models have their own unique advantages and limitations, which must be considered when they are employed in the study of pathogenesis or treatment approaches. This review provides a summary and a critical review of our current knowledge about various in vivo models of PD used to test novel therapeutic strategies.

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Animal models of the non-motor features of Parkinson's disease

Cited by 141 publications

References 171 publications

A Progressive Mouse Model of Parkinson's Disease: The Thy1-aSyn (“Line 61”) Mice

A Progressive Mouse Model of Parkinson's Disease: The Thy1-aSyn (“Line 61”) Mice

Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol

Animal Models of Parkinson's Disease: A Gateway to Therapeutics?

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