Elsevier

Neurobiology of Disease

Volume 10, Issue 3, August 2002, Pages 387-395
Neurobiology of Disease

Regular Article
Experimental Parkinsonism Modulates Multiple Genes Involved in the Transduction of Dopaminergic Signals in the Striatum

https://doi.org/10.1006/nbdi.2002.0525Get rights and content

Abstract

The irreversible loss of the dopamine-mediated control of striatal function is considered the functional substrate of the motor symptoms of Parkinson's disease. This pathological event causes a complex rearrangement of neuronal activity which involves specific dopamine-regulated cellular functions and, secondarily, several other cellular properties and transmitter systems. In the present study, we applied recently developed cDNA microarray technology to investigate the genetic correlates of the alterations produced by 6-hydroxydopamine-induced dopamine denervation in the nucleus striatum. We found that chronic dopamine denervation caused the modulation of 50 different genes involved in several cellular functions. In particular, products of the genes modulated by this experimental manipulation are involved both in the intracellular transduction of dopamine signal and in the regulation of glutamate transmission in striatal neurons, providing some information on the possible neuronal events which lead to the reorganization of glutamate transmission in the striatum of parkinsonian rats.

References (47)

  • S.M. Papa et al.

    Opposite effects of NMDA and AMPA receptor blockade on catalepsy induced by dopamine receptor antagonists

    Eur. J. Pharmacol.

    (1993)
  • R. Raisman-Vozari et al.

    Lack of change in striatal DARPP-32 levels following nigrostriatal dopaminergic lesions in animals and in parkinsonian syndromes in man

    Brain Res.

    (1990)
  • R.K.W. Schwarting et al.

    Unilateral 6-hydroxydopamine lesions of mesostriatal dopamine neurons and their physiological sequelae

    Prog. Neurobiol.

    (1996)
  • J.A. Bibb et al.

    Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons

    Nature

    (1999)
  • P. Calabresi et al.

    Long-term depression in the striatum: Physiological and pharmacological characterization

    J. Neurosci.

    (1992)
  • P. Calabresi et al.

    Electrophysiology of dopamine-denervated striatal neurons: Implications for Parkinson's disease

    Brain

    (1993)
  • D. Centonze et al.

    Unilateral dopamine denervation blocks corticostriatal LTP

    J. Neurophysiol.

    (1999)
  • T.N. Chase et al.

    Neostriatal mechanisms in Parkinson's disease

    Neurology

    (1998)
  • F. Desdouits et al.

    Dopamine- and cAMP-regulated phosphoprotein DARPP-32: Phosphorylation of Ser-137 by casein kinase I inhibits dephosphorylation of Thr-34 by calcineurin

    Proc. Natl. Acad. Sci. USA

    (1995)
  • A.W. Dunah et al.

    Alterations in subunit expression, composition, and phosphorylation of striatal N-methyl-d-aspartate glutamate receptors in a rat 6-hydroxydopamine model of Parkinson's disease

    Mol. Pharmacol.

    (2000)
  • A. Fernandez et al.

    Protein phosphatase type-1, not type-2A, modulates actin microfilament integrity and myosin light chain phosphorylation in living nonmuscle cells

    J. Cell Biol.

    (1990)
  • J.A. Girault et al.

    Phosphorylation of DARPP-32, a dopamine- and cAMP-regulated phosphoprotein, by casein kinase II

    J. Biol. Chem.

    (1989)
  • J.A. Girault et al.

    Striatal phosphoproteins in Parkinson disease and progressive supranuclear palsy

    Proc. Natl. Acad. Sci. USA

    (1989)

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