5-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson’s disease.
Neurobiology of Disease. 2006-07-01; 23(1): 77-86
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1. Neurobiol Dis. 2006 Jul;23(1):77-86. Epub 2006 Mar 20.
5-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and
macaque models of Parkinson’s disease.
Bezard E(1), Gerlach I, Moratalla R, Gross CE, Jork R.
(1)CNRS UMR 5543, Laboratoire de Physiologie et Physiopathologie de la
Signalisation Cellulaire, Université de Bordeaux 2, 146 rue Leo Saignat, 33076
Bordeaux Cedex, France.
Excitotoxicity-mediated cell death is involved in Parkinson’s disease (PD).
5-HT1A receptor agonists can protect from such mechanisms. The current study
demonstrates that the 5-HT1A agonists BAY 639044 and repinotan have
neuroprotective effects in a subacute
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In
addition, we also show that both compounds delay the appearance of parkinsonian
motor abnormalities in a MPTP monkey model that recapitulates the progressive
nature of PD. Thus, BAY 639044 or repinotan treatment was initiated when there
was 30% neuronal death in the substantia nigra pars compacta, and nerve terminal
loss in the striatum was 40%, i.e., compatible with the clinical situation where
early symptomatic patients would receive such a treatment. The delay in
appearance of parkinsonian motor abnormalities is a consequence of partial
neuroprotection of nigrostriatal dopamine neurons, both at neuronal and terminal
levels as shown for BAY 639044. These results suggest that 5-HT1A agonists, such
as BAY 639044, may protect from neurodegeneration and delay the worsening of
motor symptoms in Parkinson patients.
PMID: 16545572 [Indexed for MEDLINE]