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 : 000367 ( PascalFrancis/Corpus ); précédent : 000366; suivant : 000368The 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 ; Aderbal S. Jr Aguiar ; Eduardo L. G. Moreira ; Filipe C. Matheus ; Adalberto A. Castro ; Roger Walz ; Andreza F. De Bem ; Alexandra Latini ; Carla I. Tasca ; Marcelo Farina ; Rita Raisman-VozariSource :
- Current pharmaceutical design : (Print) [ 1381-6128 ] ; 2011.
Descripteurs français
- Pascal (Inist)
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.
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NO : | PASCAL 11-0416745 INIST |
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ET : | 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 |
AU : | PREDIGER (Rui D. S.); AGUIAR (Aderbal S. JR); MOREIRA (Eduardo L. G.); MATHEUS (Filipe C.); CASTRO (Adalberto A.); WALZ (Roger); DE BEM (Andreza F.); LATINI (Alexandra); TASCA (Carla I.); FARINA (Marcelo); RAISMAN-VOZARI (Rita); HERRADON (Gonzalo) |
AF : | Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC/Florianópolis-SC/Brésil (1 aut., 2 aut., 4 aut.); Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário, Universidade Federal de Santa Catarina, UFSC/Florianópolis, SC/Brésil (1 aut., 3 aut., 6 aut., 8 aut., 9 aut., 10 aut.); Departamento de Bioquímica, Universidade Federal de Santa Catarina, UFSC/Florianópolis, SC/Brésil (5 aut., 7 aut., 8 aut., 9 aut., 10 aut.); Departamento de Clínica Médica, Hospital Universitário, Universidade Federal de Santa Catarina, UFSC/Florianópolis, SC/Brésil (6 aut.); 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/Paris/France (11 aut.); Department of Pharmaceutical and Food Sciences, Faculty of Pharmacy, University San Pablo CEU/Madrid/Espagne (1 aut.) |
DT : | Publication en série; Niveau analytique |
SO : | Current pharmaceutical design : (Print); ISSN 1381-6128; Emirats Arabes Unis; Da. 2011; Vol. 17; No. 5; Pp. 489-507; Bibl. 212 ref. |
LA : | Anglais |
EA : | 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. |
CC : | 002B17G; 002B17A01; 002B02B06 |
FD : | Voie intranasale; Neurotoxine; Rodentia; Animal; Modèle animal; Neuroprotecteur; Maladie de Parkinson; Trouble moteur; Pathogénie; Antiparkinsonien; Médicament; Article synthèse; MPTP |
FG : | Toxine; Mammalia; Vertebrata; Maladie dégénérative; Pathologie du système nerveux; Pathologie de l'encéphale; Syndrome extrapyramidal; Pathologie du système nerveux central; Trouble neurologique |
ED : | Intranasal administration; Neurotoxin; Rodentia; Animal; Animal model; Neuroprotective agent; Parkinson disease; Motor system disorder; Pathogenesis; Antiparkinson agent; Drug; Review |
EG : | Toxin; Mammalia; Vertebrata; Degenerative disease; Nervous system diseases; Cerebral disorder; Extrapyramidal syndrome; Central nervous system disease; Neurological disorder |
SD : | Vía intranasal; Neurotoxina; Rodentia; Animal; Modelo animal; Neuroprotector; Parkinson enfermedad; Trastorno motor; Patogenia; Antiparkinsoniano; Medicamento; Artículo síntesis |
LO : | INIST-26320.354000189800790070 |
ID : | 11-0416745 |
Links to Exploration step
Pascal:11-0416745Le 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>
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<author><name sortKey="Farina, Marcelo" sort="Farina, Marcelo" uniqKey="Farina M" first="Marcelo" last="Farina">Marcelo Farina</name>
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<author><name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name>
<affiliation><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>
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<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>
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<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>
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<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>
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<fA09 i1="01" i2="1" l="ENG"><s1>Novel Therapeutic Strategies in Neural Diseases Uncover Unexpected Disease Connections: From Neurodegeneration and Addiction to Pain and Depression</s1>
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<fA11 i1="01" i2="1"><s1>PREDIGER (Rui D. S.)</s1>
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<fA12 i1="01" i2="1"><s1>HERRADON (Gonzalo)</s1>
<s9>ed.</s9>
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<fA14 i1="01"><s1>Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC</s1>
<s2>Florianópolis-SC</s2>
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<fA14 i1="04"><s1>Departamento de Clínica Médica, Hospital Universitário, Universidade Federal de Santa Catarina, UFSC</s1>
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<sZ>6 aut.</sZ>
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<s2>Paris</s2>
<s3>FRA</s3>
<sZ>11 aut.</sZ>
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<fA15 i1="01"><s1>Department of Pharmaceutical and Food Sciences, Faculty of Pharmacy, University San Pablo CEU</s1>
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<fC01 i1="01" l="ENG"><s0>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.</s0>
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<server><NO>PASCAL 11-0416745 INIST</NO>
<ET>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</ET>
<AU>PREDIGER (Rui D. S.); AGUIAR (Aderbal S. JR); MOREIRA (Eduardo L. G.); MATHEUS (Filipe C.); CASTRO (Adalberto A.); WALZ (Roger); DE BEM (Andreza F.); LATINI (Alexandra); TASCA (Carla I.); FARINA (Marcelo); RAISMAN-VOZARI (Rita); HERRADON (Gonzalo)</AU>
<AF>Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, UFSC/Florianópolis-SC/Brésil (1 aut., 2 aut., 4 aut.); Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário, Universidade Federal de Santa Catarina, UFSC/Florianópolis, SC/Brésil (1 aut., 3 aut., 6 aut., 8 aut., 9 aut., 10 aut.); Departamento de Bioquímica, Universidade Federal de Santa Catarina, UFSC/Florianópolis, SC/Brésil (5 aut., 7 aut., 8 aut., 9 aut., 10 aut.); Departamento de Clínica Médica, Hospital Universitário, Universidade Federal de Santa Catarina, UFSC/Florianópolis, SC/Brésil (6 aut.); 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/Paris/France (11 aut.); Department of Pharmaceutical and Food Sciences, Faculty of Pharmacy, University San Pablo CEU/Madrid/Espagne (1 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Current pharmaceutical design : (Print); ISSN 1381-6128; Emirats Arabes Unis; Da. 2011; Vol. 17; No. 5; Pp. 489-507; Bibl. 212 ref.</SO>
<LA>Anglais</LA>
<EA>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.</EA>
<CC>002B17G; 002B17A01; 002B02B06</CC>
<FD>Voie intranasale; Neurotoxine; Rodentia; Animal; Modèle animal; Neuroprotecteur; Maladie de Parkinson; Trouble moteur; Pathogénie; Antiparkinsonien; Médicament; Article synthèse; MPTP</FD>
<FG>Toxine; Mammalia; Vertebrata; Maladie dégénérative; Pathologie du système nerveux; Pathologie de l'encéphale; Syndrome extrapyramidal; Pathologie du système nerveux central; Trouble neurologique</FG>
<ED>Intranasal administration; Neurotoxin; Rodentia; Animal; Animal model; Neuroprotective agent; Parkinson disease; Motor system disorder; Pathogenesis; Antiparkinson agent; Drug; Review</ED>
<EG>Toxin; Mammalia; Vertebrata; Degenerative disease; Nervous system diseases; Cerebral disorder; Extrapyramidal syndrome; Central nervous system disease; Neurological disorder</EG>
<SD>Vía intranasal; Neurotoxina; Rodentia; Animal; Modelo animal; Neuroprotector; Parkinson enfermedad; Trastorno motor; Patogenia; Antiparkinsoniano; Medicamento; Artículo síntesis</SD>
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<ID>11-0416745</ID>
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