The Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP): A New Rodent Model to Test Palliative and Neuroprotective Agents for Parkinson's disease
Identifieur interne : 001806 ( Main/Exploration ); précédent : 001805; suivant : 001807The Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP): A New Rodent Model to Test Palliative and Neuroprotective Agents for Parkinson's disease
Auteurs : Rui D. S. Prediger [Brésil] ; Aderbal S. Jr Aguiar [Brésil] ; Eduardo L. G. Moreira [Brésil] ; Filipe C. Matheus [Brésil] ; Adalberto A. Castro [Brésil] ; Roger Walz [Brésil] ; Andreza F. De Bem [Brésil] ; Alexandra Latini [Brésil] ; Carla I. Tasca [Brésil] ; Marcelo Farina [Brésil] ; Rita Raisman-Vozari [France]Source :
- Current pharmaceutical design : (Print) [ 1381-6128 ] ; 2011.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Médicament.
English descriptors
- KwdEn :
Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting approximately 1% of the population older than 60 years. Classically, PD is considered to be a motor system disease and its diagnosis is based on the presence of a set of cardinal motor signs that are consequence of a pronounced death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Nowadays there is considerable evidence showing that non-dopaminergic degeneration also occurs in other brain areas which seems to be responsible for the deficits in olfactory, emotional and memory functions that precede the classical motor symptoms in PD. Dopamine-replacement therapy has dominated the treatment of PD and although the currently approved antiparkinsonian agents offer effective relief of the motor deficits, they have not been found to alleviate the non-motor features as well as the underlying dopaminergic neuron degeneration and thus drug efficacy is gradually lost. Another major limitation of chronic dopaminergic therapy is the numerous adverse effects such as dyskinesias, psychosis and behavioral disturbance. The development of new therapies in PD depends on the existence of representative animal models to facilitate the evaluation of new pharmacological agents before they are applied in clinical trials. We have recently proposed a new experimental model of PD consisting of a single intranasal (i.n.) administration of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 1 mg/nostril) in rodents. Our findings demonstrated that rats and mice treated intranasally with MPTP suffer impairments in olfactory, cognitive, emotional and motor functions conceivably analogous to those observed during different stages of PD. Such infusion causes time-dependent loss of tyrosine hydroxylase in the olfactory bulb and SNc, resulting in significant dopamine depletion in different brain areas. We have also identified some pathogenic mechanisms possibly involved in the neurodegeneration induced by i.n. administration of MPTP including mitochondrial dysfunction, oxidative stress, activation of apoptotic cell death mechanisms and glutamatergic excitotoxicity. Therefore, the present review attempts to provide a comprehensive picture of the i.n. MPTP model and to highlight recent findings from our group showing its potential as a valuable rodent model for testing novel drugs that may provide alternative or adjunctive treatment for both motor and non-motor symptoms relief with a reduced side-effect profile as well as the discovery of compounds to modify the course of PD.
Affiliations:
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Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">The Intranasal Administration of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP): A New Rodent Model to Test Palliative and Neuroprotective Agents for Parkinson's disease</title>
<author><name sortKey="Prediger, Rui D S" sort="Prediger, Rui D S" uniqKey="Prediger R" first="Rui D. S." last="Prediger">Rui D. S. Prediger</name>
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<affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Departamento de Bioquímica, Universidade Federal de Santa Catarina, UFSC</s1>
<s2>Florianópolis, SC</s2>
<s3>BRA</s3>
<sZ>5 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>Brésil</country>
<placeName><region type="state">Santa Catarina</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Farina, Marcelo" sort="Farina, Marcelo" uniqKey="Farina M" first="Marcelo" last="Farina">Marcelo Farina</name>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário, Universidade Federal de Santa Catarina, UFSC</s1>
<s2>Florianópolis, SC</s2>
<s3>BRA</s3>
<sZ>1 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>Brésil</country>
<placeName><region type="state">Santa Catarina</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Departamento de Bioquímica, Universidade Federal de Santa Catarina, UFSC</s1>
<s2>Florianópolis, SC</s2>
<s3>BRA</s3>
<sZ>5 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>Brésil</country>
<placeName><region type="state">Santa Catarina</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name>
<affiliation wicri:level="3"><inist:fA14 i1="05"><s1>UMR 975 INSERM - Université Pierre et Marie Curie. Centre de Recheche de l'Institut du cerveau et de la moelle épinière CRICM Thérapeutique Expérimentale de La neurodégénérescence. Hôpital de la Salpêtrière</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Current pharmaceutical design : (Print)</title>
<title level="j" type="abbreviated">Curr. pharm. des. : (Print)</title>
<idno type="ISSN">1381-6128</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Current pharmaceutical design : (Print)</title>
<title level="j" type="abbreviated">Curr. pharm. des. : (Print)</title>
<idno type="ISSN">1381-6128</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal</term>
<term>Animal model</term>
<term>Antiparkinson agent</term>
<term>Drug</term>
<term>Intranasal administration</term>
<term>Motor system disorder</term>
<term>Neuroprotective agent</term>
<term>Neurotoxin</term>
<term>Parkinson disease</term>
<term>Pathogenesis</term>
<term>Review</term>
<term>Rodentia</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Voie intranasale</term>
<term>Neurotoxine</term>
<term>Rodentia</term>
<term>Animal</term>
<term>Modèle animal</term>
<term>Neuroprotecteur</term>
<term>Maladie de Parkinson</term>
<term>Trouble moteur</term>
<term>Pathogénie</term>
<term>Antiparkinsonien</term>
<term>Médicament</term>
<term>Article synthèse</term>
<term>MPTP</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Médicament</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting approximately 1% of the population older than 60 years. Classically, PD is considered to be a motor system disease and its diagnosis is based on the presence of a set of cardinal motor signs that are consequence of a pronounced death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Nowadays there is considerable evidence showing that non-dopaminergic degeneration also occurs in other brain areas which seems to be responsible for the deficits in olfactory, emotional and memory functions that precede the classical motor symptoms in PD. Dopamine-replacement therapy has dominated the treatment of PD and although the currently approved antiparkinsonian agents offer effective relief of the motor deficits, they have not been found to alleviate the non-motor features as well as the underlying dopaminergic neuron degeneration and thus drug efficacy is gradually lost. Another major limitation of chronic dopaminergic therapy is the numerous adverse effects such as dyskinesias, psychosis and behavioral disturbance. The development of new therapies in PD depends on the existence of representative animal models to facilitate the evaluation of new pharmacological agents before they are applied in clinical trials. We have recently proposed a new experimental model of PD consisting of a single intranasal (i.n.) administration of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 1 mg/nostril) in rodents. Our findings demonstrated that rats and mice treated intranasally with MPTP suffer impairments in olfactory, cognitive, emotional and motor functions conceivably analogous to those observed during different stages of PD. Such infusion causes time-dependent loss of tyrosine hydroxylase in the olfactory bulb and SNc, resulting in significant dopamine depletion in different brain areas. We have also identified some pathogenic mechanisms possibly involved in the neurodegeneration induced by i.n. administration of MPTP including mitochondrial dysfunction, oxidative stress, activation of apoptotic cell death mechanisms and glutamatergic excitotoxicity. Therefore, the present review attempts to provide a comprehensive picture of the i.n. MPTP model and to highlight recent findings from our group showing its potential as a valuable rodent model for testing novel drugs that may provide alternative or adjunctive treatment for both motor and non-motor symptoms relief with a reduced side-effect profile as well as the discovery of compounds to modify the course of PD.</div>
</front>
</TEI>
<affiliations><list><country><li>Brésil</li>
<li>France</li>
</country>
<region><li>Santa Catarina</li>
<li>Île-de-France</li>
</region>
<settlement><li>Paris</li>
</settlement>
</list>
<tree><country name="Brésil"><region name="Santa Catarina"><name sortKey="Prediger, Rui D S" sort="Prediger, Rui D S" uniqKey="Prediger R" first="Rui D. S." last="Prediger">Rui D. S. Prediger</name>
</region>
<name sortKey="Aguiar, Aderbal S Jr" sort="Aguiar, Aderbal S Jr" uniqKey="Aguiar A" first="Aderbal S. Jr" last="Aguiar">Aderbal S. Jr Aguiar</name>
<name sortKey="Castro, Adalberto A" sort="Castro, Adalberto A" uniqKey="Castro A" first="Adalberto A." last="Castro">Adalberto A. Castro</name>
<name sortKey="De Bem, Andreza F" sort="De Bem, Andreza F" uniqKey="De Bem A" first="Andreza F." last="De Bem">Andreza F. De Bem</name>
<name sortKey="Farina, Marcelo" sort="Farina, Marcelo" uniqKey="Farina M" first="Marcelo" last="Farina">Marcelo Farina</name>
<name sortKey="Farina, Marcelo" sort="Farina, Marcelo" uniqKey="Farina M" first="Marcelo" last="Farina">Marcelo Farina</name>
<name sortKey="Latini, Alexandra" sort="Latini, Alexandra" uniqKey="Latini A" first="Alexandra" last="Latini">Alexandra Latini</name>
<name sortKey="Latini, Alexandra" sort="Latini, Alexandra" uniqKey="Latini A" first="Alexandra" last="Latini">Alexandra Latini</name>
<name sortKey="Matheus, Filipe C" sort="Matheus, Filipe C" uniqKey="Matheus F" first="Filipe C." last="Matheus">Filipe C. Matheus</name>
<name sortKey="Moreira, Eduardo L G" sort="Moreira, Eduardo L G" uniqKey="Moreira E" first="Eduardo L. G." last="Moreira">Eduardo L. G. Moreira</name>
<name sortKey="Prediger, Rui D S" sort="Prediger, Rui D S" uniqKey="Prediger R" first="Rui D. S." last="Prediger">Rui D. S. Prediger</name>
<name sortKey="Tasca, Carla I" sort="Tasca, Carla I" uniqKey="Tasca C" first="Carla I." last="Tasca">Carla I. Tasca</name>
<name sortKey="Tasca, Carla I" sort="Tasca, Carla I" uniqKey="Tasca C" first="Carla I." last="Tasca">Carla I. Tasca</name>
<name sortKey="Walz, Roger" sort="Walz, Roger" uniqKey="Walz R" first="Roger" last="Walz">Roger Walz</name>
<name sortKey="Walz, Roger" sort="Walz, Roger" uniqKey="Walz R" first="Roger" last="Walz">Roger Walz</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name>
</region>
</country>
</tree>
</affiliations>
</record>
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