The MPTP neurotoxic lesion model of Parkinson's disease activates the apolipoprotein E cascade in the mouse brain

Domenger, Dorothée; Dea, Doris; Théroux, Louise; Moquin, Luc; Gratton, Alain; Poirier, Judes

doi:10.1016/j.expneurol.2011.11.031

Cited by 21 publications

(14 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…During memory encoding, we found reduced brain activity within the temporo-parietal network and impaired performance in carriers of APOE4 . Although the number of APOE4 carriers was small, this observation is consistent with the literature (Pulkes et al , 2011; Domenger et al , 2012; Federoff et al , 2012; Peplonska et al , 2013; Multhammer et al , 2014). It has been suggested that APOE4 Parkinson’s disease carriers present more severe cortical atrophy (Wakabayashi et al , 1998; Li et al , 2004) and more frequent cognitive decline than patients without an APOE4 allele (Irwin et al , 2012).…”

Section: Discussionsupporting

confidence: 92%

Genetic impact on cognition and brain function in newly diagnosed Parkinson’s disease: ICICLE-PD study

Nombela

Rowe

Winder‐Rhodes

et al. 2014

Brain

135

134

View full text Add to dashboard Cite

See Dujardin (doi:) for a scientific commentary on this article. Nombela et al. present data from the ICICLE-PD study of cognition in newly diagnosed Parkinson’s disease. Consistent with the ‘Dual Syndrome’ hypothesis, impairments in executive function reflect a frontal dopaminergic syndrome modulated by COMT genotype, while visuospatial and memory deficits reflect disruption of temporo-parietal systems modulated by MAPT and APOE.

show abstract

Section: Discussionsupporting

confidence: 92%

Genetic impact on cognition and brain function in newly diagnosed Parkinson’s disease: ICICLE-PD study

Nombela

Rowe

Winder‐Rhodes

et al. 2014

Brain

135

134

View full text Add to dashboard Cite

show abstract

“…The lack of robust behavioral changes may be attributable to the lower absolute dose and/or to the functional recovery that takes place following MPTP lesioning. Indeed, the sprouting and regeneration of new dopaminergic fibers, accompanied by functional recovery, is a well-established phenomenon that has been shown to begin within 24 hours of the last injection (Bezard et al , 2000a; Bezard & Gross, 1998; Bezard et al , 2000b; Bohn et al , 1988; Domenger et al , 2012; Kang et al , 2007; Mitsumoto et al , 1998; Schneider & Yuwiler, 1989). …”

Section: Discussionmentioning

confidence: 99%

Targeted deletion of GD3 synthase protects against MPTP‐induced neurodegeneration

Akkhawattanangkul

Maiti

Xue

et al. 2017

Genes Brain and Behavior

View full text Add to dashboard Cite

Parkinson’s disease is a debilitating neurodegenerative condition for which there is no cure. Converging evidence implicates gangliosides in the pathogenesis of several neurodegenerative diseases, suggesting a potential new class of therapeutic targets. We have shown that interventions that simultaneously increase the neuroprotective GM1 ganglioside and decrease the pro-apoptotic GD3 ganglioside—such as inhibition of GD3 synthase (GD3S) or administration of sialidase—are neuroprotective in vitro and in a number of preclinical models. In the present study we investigated the effects of GD3S deletion on parkinsonism induced by 1-Methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP was administered to GD3S−/− mice or controls using a subchronic regimen consisting of three series of low-dose injections (11 mg/kg/day x 5 days each, 3 weeks apart), and motor function was assessed after each. The typical battery of tests used to assess parkinsonism failed to detect deficits in MPTP-treated mice. More sensitive measures—such as the force-plate actimeter and treadmill gait parameters—detected subtle effects of MPTP, some of which were absent in mice lacking GD3S. In wild-type mice MPTP destroyed 53% of the tyrosine-hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNc) and reduced striatal dopamine 60.7%. In contrast, lesion size was only 22.5% in GD3S−/− mice and striatal dopamine was reduced by 37.2%. Stereological counts of Nissl-positive SNc neurons that did not express TH suggest that neuroprotection was complete but TH expression was suppressed in some cells. These results demonstrate that inhibition of GD3S has neuroprotective properties in the MPTP model may warrant further investigation as a therapeutic target.

show abstract

“…There are fascinating mechanisms that may be relevant, for example, a large clinical study provided evidence that lipids and lipoproteins may affect dopamine neuron–specific signaling cascades . Other studies show that cholesterol recycling may be linked to PD, and related genes are associated with increased PD risk or are affected in animal models of PD or PD itself …”

Section: Contributions From the Basic Sciencesmentioning

confidence: 99%

Understanding the Links Between Cardiovascular Disease and Parkinson's Disease

et al. 2019

View full text Add to dashboard Cite

Studies investigating the associations between genetic or environmental factors and Parkinson's disease (PD) have uncovered a number of factors shared with cardiovascular disease, either as risk factors or manifestations of cardiovascular disease itself. Older age, male sex, and possibly type 2 diabetes are examples. On the other hand, coffee consumption and physical activity are each associated with a lower risk of both PD and cardiovascular disease. This observation raises questions about the underlying pathophysiological links between cardiovascular disease and PD. There is evidence for common mechanisms in the areas of glucose metabolism, cellular stress, lipid metabolism, and inflammation. On the other hand, smoking and total/low‐density lipoprotein cholesterol appear to have opposite associations with cardiovascular disease and PD. Thus, it is uncertain whether the treatment of cardiovascular risk factors will impact on the onset or progression of PD. The available data suggest that a nuanced approach is necessary to manage risk factors such as cholesterol levels once the associations are better understood. Ultimately, the choice of therapy may be tailored to a patient's comorbidity profile. This review presents the epidemiological evidence for both concordant and discordant associations between cardiovascular disease and PD, discusses the cellular and metabolic processes that may underlie these links, and explores the implications this has for patient care and future research. © 2019 International Parkinson and Movement Disorder Society

show abstract

The MPTP neurotoxic lesion model of Parkinson's disease activates the apolipoprotein E cascade in the mouse brain

Cited by 21 publications

References 66 publications

Genetic impact on cognition and brain function in newly diagnosed Parkinson’s disease: ICICLE-PD study

Genetic impact on cognition and brain function in newly diagnosed Parkinson’s disease: ICICLE-PD study

Targeted deletion of GD3 synthase protects against MPTP‐induced neurodegeneration

Understanding the Links Between Cardiovascular Disease and Parkinson's Disease

Contact Info

Product

Resources

About