Upregulation of striatal preproenkephalin gene expression occurs before the appearance of parkinsonian signs in 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine monkeys.
Neurobiology of Disease. 2001-04-01; 8(2): 343-350
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1. Neurobiol Dis. 2001 Apr;8(2):343-50.
Upregulation of striatal preproenkephalin gene expression occurs before the
appearance of parkinsonian signs in 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine
Bezard E(1), Ravenscroft P, Gross CE, Crossman AR, Brotchie JM.
(1)Manchester Movement Disorder Laboratory, Division of Neuroscience, School of
Biological Sciences, University of Manchester, 1.124 Stopford Building,
Manchester, M13 9 PT, United Kingdom.
GABA and enkephalin-utilizing efferents from the striatum to the external segment
of the pallidal complex (GPe) are thought to be overactive in Parkinson’s disease
(PD). This overactivity is generally held to play a major role in the genesis of
parkinsonian symptoms, which are thought to appear when dopaminergic neuronal
death exceeds a critical threshold. Little is known, however, regarding the
activity of this pathway during disease progression and more particularly, prior
to the emergence of parkinsonian symptoms. In order to test the hypothesis that
an upregulation of striatal preproenkephalin-A (PPE-A) mRNA levels occurs before
the appearance of parkinsonian motor disabilities, the present study assessed
PPE-A mRNA expression and striatal dopamine (DA) content following a chronic
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration protocol in
monkeys that produces a progressive parkinsonian state. Groups ranged from normal
to full parkinsonian through asymptomatic lesioned monkeys. The key finding of
this study is that PPE-A expression is already upregulated in
asymptomatic-lesioned monkeys showing a marked DA depletion (56%). Importantly,
this up-regulation is restricted to motor regions of the basal ganglia circuitry.
The increased PPE-A mRNA expression observed in asymptomatic, but DA-depleted
animals, supports our initial hypothesis of such an upregulation occurring before
the appearance of parkinsonian motor disabilities. Furthermore, when considered
with recent electrophysiological and histochemical data, these findings question
the functional significance of upregulated enkephalin transmission in the
indirect striatopallidal pathway.
Copyright 2001 Academic Press.
PMID: 11300729 [Indexed for MEDLINE]