Biochemical and morphological consequences of human α-synuclein expression in a mouse α-synuclein null background

Prasad, Kavita; Tarasewicz, Elizabeth; Ohman‐Strickland, Pamela; O’Neill, Michael; Mitchell, Stephen N.; Merchant, Kalpana; Tep, Samnang; Hilton, Kenneth; Datwani, Akash; Buttini, Manuel; Mueller-Steiner, Sarah; Richfield, Eric K.

doi:10.1111/j.1460-9568.2010.07558.x

Cited by 18 publications

(10 citation statements)

References 85 publications

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“…Although no significant differences between control and α -syn KO mice were found for evoked calcium activity and evoked spiking activity, α -syn KO mice exhibited a nonsignificant trend toward increases in the frequency and amplitude of spontaneous activity and in the fraction of imaged neurons exhibiting calcium alterations. Previous studies in α -syn KO mice reported only a mild synaptic deficit with subtle alterations in dopaminergic transmitter release (Abeliovich et al, 2000; Prasad et al, 2011). However, α -syn plays a role in the normal synaptic assembly.…”

Section: Discussionmentioning

confidence: 94%

In Vivo Alterations in Calcium Buffering Capacity in Transgenic Mouse Model of Synucleinopathy

Reznichenko¹,

Cheng²,

Nizar³

et al. 2012

Journal of Neuroscience

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Abnormal accumulation of α-synuclein is centrally involved in the pathogenesis of many disorders with Parkinsonism and dementia. Previous in vitro studies suggest that α-synuclein dysregulates intracellular calcium. However, it is unclear whether these alterations occur in vivo. For this reason, we investigated calcium dynamics in transgenic mice expressing human WT α-synuclein using two-photon microscopy. We imaged spontaneous and stimulus-induced neuronal activity in the barrel cortex. Transgenic mice exhibited augmented, long-lasting calcium transients characterized by considerable deviation from the exponential decay. The most evident pathology was observed in response to a repetitive stimulation in which subsequent stimuli were presented before relaxation of calcium signal to the baseline. These alterations were detected in the absence of significant increase in neuronal spiking response compared with age-matched controls, supporting the possibility that α-synuclein promoted alterations in calcium dynamics via interference with intracellular buffering mechanisms. The characteristic shape of calcium decay and augmented response during repetitive stimulation can serve as in vivo imaging biomarkers in this model of neurodegeneration, to monitor progression of the disease and screen candidate treatment strategies.

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Section: Discussionmentioning

confidence: 94%

In Vivo Alterations in Calcium Buffering Capacity in Transgenic Mouse Model of Synucleinopathy

Reznichenko¹,

Cheng²,

Nizar³

et al. 2012

Journal of Neuroscience

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“…However, in a model with double mutant (A30P/A53T), apparent neurites dystrophy was reported. This phenotype was accompanied by deterioration in motor activity and neuronal aggregates [61]. These models are useful to elucidate the function of α-Synuclein related neurodegeneration, though the clinical relevance of this model for PD is questionable.…”

Section: α-Synucleinmentioning

confidence: 99%

Historical Perspective: Models of Parkinson’s Disease

Chia

Tan

Chao

2020

IJMS

229

168

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Parkinson’s disease (PD) is the most common movement disorder with motor and nonmotor signs. The current therapeutic regimen for PD is mainly symptomatic as the etio-pathophysiology has not been fully elucidated. A variety of animal models has been generated to study different aspects of the disease for understanding the pathogenesis and therapeutic development. The disease model can be generated through neurotoxin-based or genetic-based approaches in a wide range of animals such as non-human primates (NHP), rodents, zebrafish, Caenorhabditis (C.) elegans, and drosophila. Cellular-based disease model is frequently used because of the ease of manipulation and suitability for large-screen assays. In neurotoxin-induced models, chemicals such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, and paraquat are used to recapitulate the disease. Genetic manipulation of PD-related genes, such as α-Synuclein(SNCA), Leucine-rich repeat kinase 2 (LRRK2), Pten-Induced Kinase 1 (PINK1), Parkin(PRKN), and Protein deglycase (DJ-1) Are used in the transgenic models. An emerging model that combines both genetic- and neurotoxin-based methods has been generated to study the role of the immune system in the pathogenesis of PD. Here, we discuss the advantages and limitations of the different PD models and their utility for different research purposes.

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“…Based on these significant findings, researchers have started to model PD based on the overexpression of the wild type or mutant forms of SNCA in animals. Many α-synuclein transgenic animal models have been proposed based on this model, with the subsequent experimental results revealing the pathology of PD [ 42 , 43 ]. The SNCA transgenic model can reproduce SNCA aggregation similar to that found in human PD.…”

Section: Pd Modelsmentioning

confidence: 99%

Animal Model for Lower Urinary Tract Dysfunction in Parkinson’s Disease

Kitta

Ouchi

Chiba

et al. 2020

IJMS

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Although Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and subsequent motor symptoms, various non-motor symptoms often precede these other symptoms. While motor symptoms are certainly burdensome, a wide range of non-motor symptoms have emerged as the key determinant of the quality of life in PD patients. The prevalence of lower urinary tract symptoms differs according to the study, with ranges between 27% and 63.9%. These can be influenced by the stage of disease, the presence of lower urinary tract-related comorbidities, and parallels with other manifestations of autonomic dysfunction. Animal models can provide a platform for investigating the mechanisms of PD-related dysfunction and for the assessment of novel treatment strategies. Animal research efforts have been primarily focused on PD motor signs and symptoms. However, the etiology of lower urinary tract dysfunction in PD has yet to be definitively clarified. Several animal PD models are available, each of which has a different effect on the autonomic nervous system. In this article, we review the various lower urinary tract dysfunction animal PD models. We additionally discuss techniques for determining the appropriate model for evaluating the development of lower urinary tract dysfunction treatments.

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Biochemical and morphological consequences of human α-synuclein expression in a mouse α-synuclein null background

Cited by 18 publications

References 85 publications

In Vivo Alterations in Calcium Buffering Capacity in Transgenic Mouse Model of Synucleinopathy

In Vivo Alterations in Calcium Buffering Capacity in Transgenic Mouse Model of Synucleinopathy

Historical Perspective: Models of Parkinson’s Disease

Animal Model for Lower Urinary Tract Dysfunction in Parkinson’s Disease

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