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Ventral tegmental area dopamine neurons are resistant to human mutant alpha-synuclein overexpression.

In English

Författare

  • Matthew Maingay
  • Marina Romero-Ramos
  • Manolo Carta
  • Deniz Kirik

Summary, in English

Parkinson's disease (PD) is characterized by the formation of intracytoplasmic inclusions, which contain α-synuclein (α-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 α-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 α-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.

Publiceringsår

2006

Språk

Engelska

Sidor

522-532

Publikation/Tidskrift/Serie

Neurobiology of Disease

Volym

23

Issue

3

Dokumenttyp

Artikel i tidskrift

Förlag

Elsevier

Ämne

  • Neurosciences

Nyckelord

  • Cell death
  • Mesolimbic
  • α-synuclein
  • Recombinant adeno-associated virus
  • Parkinson's disease
  • Stereology
  • Tyrosine hydroxylase
  • Open field activity

Status

Published

Forskningsgrupp

  • Brain Repair and Imaging in Neural Systems (BRAINS)

ISBN/ISSN/Övrigt

  • ISSN: 0969-9961