Immediate-early gene expression in structures outside the basal ganglia is associated to l-DOPA-induced dyskinesia.
Neurobiology of Disease. 2014-02-01; 62: 179-192
DOI: 10.1016/j.nbd.2013.09.020
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1. Neurobiol Dis. 2014 Feb;62:179-92. doi: 10.1016/j.nbd.2013.09.020. Epub 2013 Oct
6.
Immediate-early gene expression in structures outside the basal ganglia is
associated to l-DOPA-induced dyskinesia.
Bastide MF(1), Dovero S(1), Charron G(1), Porras G(1), Gross CE(1), Fernagut
PO(1), Bézard E(2).
Author information:
(1)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000
Bordeaux, France.
(2)Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33000
Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000
Bordeaux, France. Electronic address: .
Long-term l-3,4-dihydroxyphenylalanine (l-DOPA) treatment in Parkinson’s disease
(PD) leads to l-DOPA-induced dyskinesia (LID), a condition thought to primarily
involve the dopamine D1 receptor-expressing striatal medium spiny neurons.
Activation of the D1 receptor results in increased expression of several
molecular markers, in particular the members of the immediate-early gene (IEG)
family, a class of genes rapidly transcribed in response to an external stimulus.
However, several dopaminoceptive structures in the brain that are likely to be
affected by the exogenously produced DA have received little attention although
they might play a key role in mediating those l-DOPA-induced abnormal behaviours.
ΔFosB, ARC, FRA2 and Zif268 IEGs expression patterns were thus characterised,
using unbiased stereological methods, in the whole brain of dyskinetic and
non-dyskinetic rats to identify brain nuclei displaying a transcriptional
response specifically related to LID. Within the basal ganglia, the striatum and
the substantia nigra pars reticulata showed an increased expression of all four
IEGs in dyskinetic compared to non-dyskinetic rats. Outside the basal ganglia,
there was a striking increased expression of the four IEGs in the motor cortex,
the bed nucleus of the stria terminalis, the dorsal hippocampus, the pontine
nuclei, the cuneiform nucleus and the pedunculopontine nuclei. Moreover, the zona
incerta and the lateral habenula displayed an overexpression of ΔFosB, ARC and
Zif268. Among these structures, the IEG expression in the striatum, the bed
nucleus of the stria terminalis, the lateral habenula, the pontine nuclei and the
cuneiform nucleus correlate with LID severity. These results illustrate a global
transcriptional response to a dyskinetic state in the whole brain suggesting the
possible involvement of these structures in LID.
© 2013.
DOI: 10.1016/j.nbd.2013.09.020
PMID: 24103779 [Indexed for MEDLINE]