Molecular and cellular alterations in the Pitx3-deficient midbrain dopaminergic system

Molecular and cellular alterations in the Pitx3-deficient midbrain dopaminergic system Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of midbrain dopaminergic (mDA) neurons in the substantia nigra compacta (SNc). In order to provide insights into adaptive mechanisms of the mDA system in pathology, specific molecular and cellular parameters of the mDA system were studied in Pitx3-deficient Aphakia ( ak ) mice, which suffer from severe developmental failure of SNc mDA neurons. Here, we demonstrate differential changes in striatal gene expression, reflecting the specific neuronal loss in these mice. In addition, the neuronal activity of remaining mDA neurons in the ventral tegmental area (VTA) was significantly increased in ak mice. In conclusion, ak mice display specific molecular and cellular alterations in the mDA system that provide new insights in compensatory mechanisms present in mDA-associated disorders such as PD. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular and Cellular Neuroscience Elsevier

Molecular and cellular alterations in the Pitx3-deficient midbrain dopaminergic system

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Publisher
Elsevier
Copyright
Copyright © 2005 Elsevier Inc.
ISSN
1044-7431
DOI
10.1016/j.mcn.2005.07.018
Publisher site
See Article on Publisher Site

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by loss of midbrain dopaminergic (mDA) neurons in the substantia nigra compacta (SNc). In order to provide insights into adaptive mechanisms of the mDA system in pathology, specific molecular and cellular parameters of the mDA system were studied in Pitx3-deficient Aphakia ( ak ) mice, which suffer from severe developmental failure of SNc mDA neurons. Here, we demonstrate differential changes in striatal gene expression, reflecting the specific neuronal loss in these mice. In addition, the neuronal activity of remaining mDA neurons in the ventral tegmental area (VTA) was significantly increased in ak mice. In conclusion, ak mice display specific molecular and cellular alterations in the mDA system that provide new insights in compensatory mechanisms present in mDA-associated disorders such as PD.

Journal

Molecular and Cellular NeuroscienceElsevier

Published: Nov 1, 2005

References

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    Fauchey, V.; Jaber, M.; Caron, M.G.; Bloch, B.; Le Moine, C.
  • The neostriatal mosaic: multiple levels of compartmental organization
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  • Dopamine and baclofen inhibit the hyperpolarization-activated cation current in rat ventral tegmental neurones
    Jiang, Z.G.; Pessia, M.; North, R.A.
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  • Queer current and pacemaker: the hyperpolarization-activated cation current in neurons
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    Rieger, D.K.; Reichenberger, E.; McLean, W.; Sidow, A.; Olsen, B.R.
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    Roeper, J.; Pongs, O.
  • Deletion in the promoter region and altered expression of Pitx3 homeobox gene in aphakia mice
    Semina, E.V.; Murray, J.C.; Reiter, R.; Hrstka, R.F.; Graw, J.
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