Linked Life Data

18410503

Source:http://linkedlifedata.com/resource/pubmed/id/18410503

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-8-8
pubmed:abstractText
Progressive degeneration and intraneuronal Lewy bodies made of filamentous alpha-synuclein (alpha-syn) in dopaminergic cells of the nigrostriatal system are characteristics of Parkinson's disease (PD). Glucose uptake is reduced in some of the brain regions affected by PD neurodegenerative changes. Defects in mitochondrial activity in the substantia nigra have been observed in the brain of patients affected by PD and substantia nigra lesions can induce the onset of a secondary parkinsonism. Thus, energy starvation and consequently metabolic impairment to dopaminergic neurons may be related to the onset of PD. On this line, we evaluated the effect of nutrient starvation, reproduced 'in vitro' by glucose deprivation (GD), in primary mesecephalic neuronal cultures and dopaminergic-differentiated SH-SY5Y cells, to evaluate if decreased glucose support to dopaminergic cells can lead to mitochondrial damage, neurodegeneration and alpha-syn misfolding. Furthermore, we investigated the effect of dopamine (DA) treatment in the presence of a DA-uptake inhibitor or of the D(2)/D(3) receptor (D(2)R/D(3)R) agonist quinpirole on GD-treated cells, to evaluate the efficacy of these therapeutic compounds. We found that GD induced the formation of fibrillary aggregated alpha-syn inclusions containing the DA transporter in dopaminergic cells. These alterations were accompanied by dopaminergic cell death and were exacerbated by DA overload. Conversely, the block of DA uptake and D(2)R/D(3)R agonist treatment exerted neuroprotective effects. These data indicate that glucose starvation is likely involved in the induction of PD-related pathological changes in dopaminergic neurons. These changes may be counteracted by the block of DA uptake and by dopaminergic agonist treatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1471-4159
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
106
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
560-77
pubmed:meshHeading
pubmed-meshheading:18410503-Analysis of Variance, pubmed-meshheading:18410503-Animals, pubmed-meshheading:18410503-Cell Death, pubmed-meshheading:18410503-Cells, Cultured, pubmed-meshheading:18410503-Dopamine, pubmed-meshheading:18410503-Dopamine Agents, pubmed-meshheading:18410503-Dopamine Plasma Membrane Transport Proteins, pubmed-meshheading:18410503-Embryo, Mammalian, pubmed-meshheading:18410503-Formazans, pubmed-meshheading:18410503-Gene Expression Regulation, pubmed-meshheading:18410503-Glucose, pubmed-meshheading:18410503-Mesencephalon, pubmed-meshheading:18410503-Mice, pubmed-meshheading:18410503-Mitochondria, pubmed-meshheading:18410503-Nerve Degeneration, pubmed-meshheading:18410503-Nerve Tissue Proteins, pubmed-meshheading:18410503-Neurons, pubmed-meshheading:18410503-Protein Transport, pubmed-meshheading:18410503-Receptors, Dopamine D2, pubmed-meshheading:18410503-Tetrazolium Salts, pubmed-meshheading:18410503-Thiazoles, pubmed-meshheading:18410503-alpha-Synuclein
pubmed:year
2008
pubmed:articleTitle
Alpha-synuclein aggregation and cell death triggered by energy deprivation and dopamine overload are counteracted by D2/D3 receptor activation.
pubmed:affiliation
Division of Pharmacology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy. bellucci@med.unibs.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't