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Ventral tegmental area dopamine neurons are resistant to human mutant alpha-synuclein overexpression.
Neurobiol Dis. 2006 Sep; 23(3):522-32.ND

Abstract

Parkinson's disease (PD) is characterized by the formation of intracytoplasmic inclusions, which contain alpha-synuclein (alpha-syn) protein. While most profound neurodegeneration is seen in the dopamine (DA) synthesizing neurons located in the ventral midbrain, it is unclear why some DA cell groups are more susceptible than others. In the midbrain, the degeneration of the substantia nigra (SN) DA neurons is severe, whereas the involvement of the ventral tegmental area (VTA) neurons is relatively spared. In the present study, we overexpressed human A53T alpha-syn in the VTA neurons and found that A53T toxicity did not affect their survival. There was, however, a mild functional impairment seen as altered open field locomotor activity. Overexpression of A53T in the SN, on the other hand, led to profound cell loss. These results suggest that the selective susceptibility of nigral DA neurons is at least in part associated with factor(s) involved in handling of alpha-syn that is not shared by the VTA neurons. Secondly, these results highlight the fact that impaired but surviving neurons can have a substantial impact on DA-dependent behavior and should therefore be considered as a critical part of animal models where novel therapeutic interventions are tested.

Authors+Show Affiliations

Department of Experimental Medical Science, Section of Neuroscience, CNS Disease Modeling Unit, Lund University, Wallenberg Neuroscience Center, BMCA11, S-22184 Lund, Sweden. matthew.maingay@med.lu.seNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16806952

Citation

Maingay, Matthew, et al. "Ventral Tegmental Area Dopamine Neurons Are Resistant to Human Mutant Alpha-synuclein Overexpression." Neurobiology of Disease, vol. 23, no. 3, 2006, pp. 522-32.
Maingay M, Romero-Ramos M, Carta M, et al. Ventral tegmental area dopamine neurons are resistant to human mutant alpha-synuclein overexpression. Neurobiol Dis. 2006;23(3):522-32.
Maingay, M., Romero-Ramos, M., Carta, M., & Kirik, D. (2006). Ventral tegmental area dopamine neurons are resistant to human mutant alpha-synuclein overexpression. Neurobiology of Disease, 23(3), 522-32.
Maingay M, et al. Ventral Tegmental Area Dopamine Neurons Are Resistant to Human Mutant Alpha-synuclein Overexpression. Neurobiol Dis. 2006;23(3):522-32. PubMed PMID: 16806952.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ventral tegmental area dopamine neurons are resistant to human mutant alpha-synuclein overexpression. AU - Maingay,Matthew, AU - Romero-Ramos,Marina, AU - Carta,Manolo, AU - Kirik,Deniz, Y1 - 2006/06/30/ PY - 2006/02/17/received PY - 2006/04/12/revised PY - 2006/04/24/accepted PY - 2006/6/30/pubmed PY - 2006/11/2/medline PY - 2006/6/30/entrez SP - 522 EP - 32 JF - Neurobiology of disease JO - Neurobiol Dis VL - 23 IS - 3 N2 - Parkinson's disease (PD) is characterized by the formation of intracytoplasmic inclusions, which contain alpha-synuclein (alpha-syn) protein. While most profound neurodegeneration is seen in the dopamine (DA) synthesizing neurons located in the ventral midbrain, it is unclear why some DA cell groups are more susceptible than others. In the midbrain, the degeneration of the substantia nigra (SN) DA neurons is severe, whereas the involvement of the ventral tegmental area (VTA) neurons is relatively spared. In the present study, we overexpressed human A53T alpha-syn in the VTA neurons and found that A53T toxicity did not affect their survival. There was, however, a mild functional impairment seen as altered open field locomotor activity. Overexpression of A53T in the SN, on the other hand, led to profound cell loss. These results suggest that the selective susceptibility of nigral DA neurons is at least in part associated with factor(s) involved in handling of alpha-syn that is not shared by the VTA neurons. Secondly, these results highlight the fact that impaired but surviving neurons can have a substantial impact on DA-dependent behavior and should therefore be considered as a critical part of animal models where novel therapeutic interventions are tested. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/16806952/Ventral_tegmental_area_dopamine_neurons_are_resistant_to_human_mutant_alpha_synuclein_overexpression_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(06)00093-3 DB - PRIME DP - Unbound Medicine ER -