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Selective loss of dopaminergic neurons and formation of Lewy body-like aggregations in alpha-synuclein transgenic fly neuronal cultures.
Eur J Neurosci. 2006 Jun; 23(11):2908-14.EJ

Abstract

A key pathological feature of Parkinson's disease (PD) is the selective loss of dopaminergic neurons accompanied by the formation of Lewy bodies (LB). Given the complex nature of the disease, it is imperative to develop a model system suitable for molecular and cellular manipulation in order to study the mechanisms underlying the pathogenesis of PD. Here, we report that a new in vitro model of PD has been developed by using Drosophila melanogaster primary neuronal cultures expressing a human mutant alpha-synuclein (alpha-Syn; A30P). The selective loss of dopaminergic (DA) neurons was observed when alpha-Syn was pan-neuronally expressed while non-dopaminergic neurons (e.g. GABAergic) were not influenced. This degeneration was also observed even when alpha-Syn was specifically expressed in DA neurons, demonstrating alpha-Syn toxicity is DA cell-autonomous. In all experiments, cultures 5 days or older showed clear degeneration of DA neurons whereas this degeneration was not significant in 3-day-old cultures. In addition, there were intracellular aggregations in 5-day or older alpha-Syn neurons that were recognized by anti-alpha-Syn or ubiquitin antibodies, demonstrating the formation of LB-like inclusions. By contrast, no such aggregations were found in 3-day-old neurons. The results demonstrate that mutated human alpha-Syn expressed in Drosophila primary neuronal cultures causes the selective loss of DA neurons and the formation of cellular aggregations. Therefore, this is one of the first in vitro models recapitulating two important cellular features of PD and will be useful in examining mechanisms underlying selective neurodegeneration mediated by alpha-Syn.

Authors+Show Affiliations

Neuroscience Program, Department of Biological Sciences, Ohio University, Athens, 45701, USA.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16819979

Citation

Park, Soon S., and Daewoo Lee. "Selective Loss of Dopaminergic Neurons and Formation of Lewy Body-like Aggregations in Alpha-synuclein Transgenic Fly Neuronal Cultures." The European Journal of Neuroscience, vol. 23, no. 11, 2006, pp. 2908-14.
Park SS, Lee D. Selective loss of dopaminergic neurons and formation of Lewy body-like aggregations in alpha-synuclein transgenic fly neuronal cultures. Eur J Neurosci. 2006;23(11):2908-14.
Park, S. S., & Lee, D. (2006). Selective loss of dopaminergic neurons and formation of Lewy body-like aggregations in alpha-synuclein transgenic fly neuronal cultures. The European Journal of Neuroscience, 23(11), 2908-14.
Park SS, Lee D. Selective Loss of Dopaminergic Neurons and Formation of Lewy Body-like Aggregations in Alpha-synuclein Transgenic Fly Neuronal Cultures. Eur J Neurosci. 2006;23(11):2908-14. PubMed PMID: 16819979.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selective loss of dopaminergic neurons and formation of Lewy body-like aggregations in alpha-synuclein transgenic fly neuronal cultures. AU - Park,Soon S, AU - Lee,Daewoo, PY - 2006/7/6/pubmed PY - 2006/9/29/medline PY - 2006/7/6/entrez SP - 2908 EP - 14 JF - The European journal of neuroscience JO - Eur J Neurosci VL - 23 IS - 11 N2 - A key pathological feature of Parkinson's disease (PD) is the selective loss of dopaminergic neurons accompanied by the formation of Lewy bodies (LB). Given the complex nature of the disease, it is imperative to develop a model system suitable for molecular and cellular manipulation in order to study the mechanisms underlying the pathogenesis of PD. Here, we report that a new in vitro model of PD has been developed by using Drosophila melanogaster primary neuronal cultures expressing a human mutant alpha-synuclein (alpha-Syn; A30P). The selective loss of dopaminergic (DA) neurons was observed when alpha-Syn was pan-neuronally expressed while non-dopaminergic neurons (e.g. GABAergic) were not influenced. This degeneration was also observed even when alpha-Syn was specifically expressed in DA neurons, demonstrating alpha-Syn toxicity is DA cell-autonomous. In all experiments, cultures 5 days or older showed clear degeneration of DA neurons whereas this degeneration was not significant in 3-day-old cultures. In addition, there were intracellular aggregations in 5-day or older alpha-Syn neurons that were recognized by anti-alpha-Syn or ubiquitin antibodies, demonstrating the formation of LB-like inclusions. By contrast, no such aggregations were found in 3-day-old neurons. The results demonstrate that mutated human alpha-Syn expressed in Drosophila primary neuronal cultures causes the selective loss of DA neurons and the formation of cellular aggregations. Therefore, this is one of the first in vitro models recapitulating two important cellular features of PD and will be useful in examining mechanisms underlying selective neurodegeneration mediated by alpha-Syn. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/16819979/Selective_loss_of_dopaminergic_neurons_and_formation_of_Lewy_body_like_aggregations_in_alpha_synuclein_transgenic_fly_neuronal_cultures_ L2 - https://doi.org/10.1111/j.1460-9568.2006.04844.x DB - PRIME DP - Unbound Medicine ER -