5-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson's disease
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-tetrahydro...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2006-07-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996106000349 |
| _version_ | 1818648781022822400 |
|---|---|
| author | Erwan Bezard Irene Gerlach Rosario Moratalla Christian E. Gross Reinhard Jork |
| author_facet | Erwan Bezard Irene Gerlach Rosario Moratalla Christian E. Gross Reinhard Jork |
| author_sort | Erwan Bezard |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T01:23:53Z |
| format | Article |
| id | doaj.art-2ee4aa71c51b4daa84382af4db728c31 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T01:23:53Z |
| publishDate | 2006-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-2ee4aa71c51b4daa84382af4db728c312022-12-21T22:08:45ZengElsevierNeurobiology of Disease1095-953X2006-07-0123177865-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson's diseaseErwan Bezard0Irene Gerlach1Rosario Moratalla2Christian E. Gross3Reinhard Jork4CNRS UMR 5543, Laboratoire de Physiologie et Physiopathologie de la Signalisation Cellulaire, Université de Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux Cedex, France; Corresponding author. Fax: +33556901421.BAYERHealthCare AG, Pharma Product Development, Wuppertal, GermanyInstituto Cajal, CSIC, Madrid, SpainCNRS UMR 5543, Laboratoire de Physiologie et Physiopathologie de la Signalisation Cellulaire, Université de Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux Cedex, FranceBAYERHealthCare AG, Pharma Product Development, Wuppertal, GermanyExcitotoxicity-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.http://www.sciencedirect.com/science/article/pii/S0969996106000349StereologySubstantia nigraDopamine transporterCytochrome oxidaseDorsal raphe nucleus |
| spellingShingle | Erwan Bezard Irene Gerlach Rosario Moratalla Christian E. Gross Reinhard Jork 5-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson's disease Neurobiology of Disease Stereology Substantia nigra Dopamine transporter Cytochrome oxidase Dorsal raphe nucleus |
| title | 5-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson's disease |
| title_full | 5-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson's disease |
| title_fullStr | 5-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson's disease |
| title_full_unstemmed | 5-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson's disease |
| title_short | 5-HT1A receptor agonist-mediated protection from MPTP toxicity in mouse and macaque models of Parkinson's disease |
| title_sort | 5 ht1a receptor agonist mediated protection from mptp toxicity in mouse and macaque models of parkinson s disease |
| topic | Stereology Substantia nigra Dopamine transporter Cytochrome oxidase Dorsal raphe nucleus |
| url | http://www.sciencedirect.com/science/article/pii/S0969996106000349 |
| work_keys_str_mv | AT erwanbezard 5ht1areceptoragonistmediatedprotectionfrommptptoxicityinmouseandmacaquemodelsofparkinsonsdisease AT irenegerlach 5ht1areceptoragonistmediatedprotectionfrommptptoxicityinmouseandmacaquemodelsofparkinsonsdisease AT rosariomoratalla 5ht1areceptoragonistmediatedprotectionfrommptptoxicityinmouseandmacaquemodelsofparkinsonsdisease AT christianegross 5ht1areceptoragonistmediatedprotectionfrommptptoxicityinmouseandmacaquemodelsofparkinsonsdisease AT reinhardjork 5ht1areceptoragonistmediatedprotectionfrommptptoxicityinmouseandmacaquemodelsofparkinsonsdisease |