alpha-synuclein and lyoniside

alpha-synuclein has been researched along with lyoniside* in 3 studies

Other Studies

3 other study(ies) available for alpha-synuclein and lyoniside

ArticleYear
Unilateral intranigral administration of β-sitosterol β-D-glucoside triggers pathological α-synuclein spreading and bilateral nigrostriatal dopaminergic neurodegeneration in the rat.
    Acta neuropathologica communications, 2020, 04-22, Volume: 8, Issue:1

    The spreading and accumulation of α-synuclein and dopaminergic neurodegeneration, two hallmarks of Parkinson's disease (PD), have been faithfully reproduced in rodent brains by chronic, oral administration of β-sitosterol β-D-glucoside (BSSG). We investigated whether a single injection of BSSG (6 μg BSSG/μL DMSO) in the left substantia nigra of Wistar rats causes the same effects. Mock DMSO injections and untreated rats formed control groups. We performed immunostainings against the pathological α-synuclein, the dopaminergic marker tyrosine hydroxylase (TH), the neuroskeleton marker β-III tubulin, the neurotensin receptor type 1 (NTSR1) as non-dopaminergic phenotype marker and Fluro-Jade C (F-J C) label for neurodegeneration. Using β-galactosidase (β-Gal) assay and active caspase-3 immunostaining, we assessed cell death mechanisms. Golgi-Cox staining was used to measure the density and types of dendritic spines of striatal medium spiny neurons. Motor and non-motor alterations were also evaluated. The study period comprised 15 to 120 days after the lesion. In the injured substantia nigra, BSSG caused a progressive α-synuclein aggregation and dopaminergic neurodegeneration caused by senescence and apoptosis. The α-synuclein immunoreactivity was also present within microglia cells. Decreased density of dopaminergic fibers and dendritic spines also occurred in the striatum. Remarkably, all the histopathological changes also appeared on the contralateral nigrostriatal system, and α-synuclein aggregates were present in other brain regions. Motor and non-motor behavioral alterations were progressive. Our data show that the stereotaxic BSSG administration reproduces PD α-synucleinopathy phenotype in the rat. This approach will aid in identifying the spread mechanism of α-synuclein pathology and validate anti-synucleinopathy therapies.

    Topics: alpha-Synuclein; Animals; Disease Models, Animal; Dopaminergic Neurons; Injections, Intraventricular; Nerve Degeneration; Parkinson Disease; Rats; Rats, Wistar; Sitosterols; Substantia Nigra

2020
The Progressive BSSG Rat Model of Parkinson's: Recapitulating Multiple Key Features of the Human Disease.
    PloS one, 2015, Volume: 10, Issue:10

    The development of effective neuroprotective therapies for Parkinson's disease (PD) has been severely hindered by the notable lack of an appropriate animal model for preclinical screening. Indeed, most models currently available are either acute in nature or fail to recapitulate all characteristic features of the disease. Here, we present a novel progressive model of PD, with behavioural and cellular features that closely approximate those observed in patients. Chronic exposure to dietary phytosterol glucosides has been found to be neurotoxic. When fed to rats, β-sitosterol β-d-glucoside (BSSG) triggers the progressive development of parkinsonism, with clinical signs and histopathology beginning to appear following cessation of exposure to the neurotoxic insult and continuing to develop over several months. Here, we characterize the progressive nature of this model, its non-motor features, the anatomical spread of synucleinopathy, and response to levodopa administration. In Sprague Dawley rats, chronic BSSG feeding for 4 months triggered the progressive development of a parkinsonian phenotype and pathological events that evolved slowly over time, with neuronal loss beginning only after toxin exposure was terminated. At approximately 3 months following initiation of BSSG exposure, animals displayed the early emergence of an olfactory deficit, in the absence of significant dopaminergic nigral cell loss or locomotor deficits. Locomotor deficits developed gradually over time, initially appearing as locomotor asymmetry and developing into akinesia/bradykinesia, which was reversed by levodopa treatment. Late-stage cognitive impairment was observed in the form of spatial working memory deficits, as assessed by the radial arm maze. In addition to the progressive loss of TH+ cells in the substantia nigra, the appearance of proteinase K-resistant intracellular α-synuclein aggregates was also observed to develop progressively, appearing first in the olfactory bulb, then the striatum, the substantia nigra and, finally, hippocampal and cortical regions. The slowly progressive nature of this model, together with its construct, face and predictive validity, make it ideal for the screening of potential neuroprotective therapies for the treatment of PD.

    Topics: alpha-Synuclein; Animals; Brain; Disease Models, Animal; Motor Activity; Neurons; Parkinson Disease, Secondary; Rats; Rats, Sprague-Dawley; Sitosterols

2015
Panax ginseng is neuroprotective in a novel progressive model of Parkinson's disease.
    Experimental gerontology, 2014, Volume: 50

    Panax ginseng has been used in traditional Chinese medicine for centuries. Among its various benefits is a pluripotent targeting of the various events involved in neuronal cell death. This includes anti-inflammatory, anti-oxidant, and anti-apoptotic effects. Indeed, ginseng extract and its individual ginsenosides have been demonstrated to influence a number of biochemical markers implicated in Parkinson's disease (PD) pathogenesis. We have reported previously that administration of the ginseng extract, G115, afforded robust neuroprotection in two rodent models of PD. However, these traditional rodent models are acute in nature and do accurately recapitulate the progressive nature of the disease. Chronic exposure to the dietary phytosterol glucoside, β-sitosterol β-d-glucoside (BSSG) triggers the progressive development of neurological deficits, with behavioral and cellular features that closely approximate those observed in PD patients. Clinical signs and histopathology continue to develop for several months following cessation of exposure to the neurotoxic insult. Here, we utilized this model to further characterize the neuroprotective effects of the ginseng extract, G115. Oral administration of this extract significantly reduced dopaminergic cell loss, microgliosis, and accumulation of α-synuclein aggregates. Further, G115 administration fully prevented the development of locomotor deficits, in the form of reduced locomotor activity and coordination. These results suggest that ginseng extract may be a potential neuroprotective therapy for the treatment of PD.

    Topics: alpha-Synuclein; Animals; Cell Death; Disease Models, Animal; Disease Progression; Drug Evaluation, Preclinical; Encephalitis; Female; Gait Disorders, Neurologic; Neuroprotective Agents; Panax; Parkinson Disease, Secondary; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Sitosterols; Substantia Nigra

2014