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
DOI: 10.1016/j.nbd.2006.02.003
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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.
Author information:
(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.
DOI: 10.1016/j.nbd.2006.02.003
PMID: 16545572 [Indexed for MEDLINE]