ParkinsonCanadaV1, PascalFrancis, Corpus, bibRecord, 000632

A multitarget basal ganglia dopaminergic and GABAergic transplantation strategy enhances behavioural recovery in parkinsonian rats

Identifieur interne : 000632 ( PascalFrancis/Corpus ); précédent : 000631; suivant : 000633

A multitarget basal ganglia dopaminergic and GABAergic transplantation strategy enhances behavioural recovery in parkinsonian rats

Auteurs : K. Mukhida ; M. Hong ; G. B. Miles ; T. Phillips ; B. A. Baghbaderani ; M. Mcleod ; N. Kobayashi ; A. Sen ; L. A. Behie ; R. M. Brownstone ; I. Mendez

Source :

Brain [ 0006-8950 ] ; 2008.

RBID : Pascal:08-0387596

Descripteurs français

Pascal (Inist)
- Maladie de Parkinson, Pathologie du système nerveux, Noyau gris central, Transplantation, Stratégie, Récupération, Animal, Rat, Noyau sousthalamique, GABA.

English descriptors

KwdEn :
- Animal, Basal ganglion, GABA, Nervous system diseases, Parkinson disease, Rat, Recovery, Strategy, Subthalamic nucleus, Transplantation.

Abstract

The current transplantation paradigm for Parkinson's disease that places foetal dopaminergic cells in the striatum neither normalizes neuronal activity in basal ganglia structures such as the substantia nigra (SN) and subthalamic nucleus (STN) nor leads to complete functional recovery. It was hypothesized that restoration of parkinsonian deficits requires inhibition of the pathological overactivity of the STN and SN in addition to restoration of dopaminergic activity in the striatum. To achieve inhibition, a multitargeted basal ganglia transplantation strategy using GABAergic cells derived from either foetal striatal primordia (FSP) cells or human neural precursor cells (hNPCs) expanded in suspension bioreactors was investigated. In hemiparkinsonian rats, transplantation of foetal rat dopaminergic cells in the striatum in conjunction with GABAergic grafts in the STN and/or SN promoted significant improvement in forelimb akinesia and motor function compared to transplantation of intrastriatal dopaminergic grafts alone or in conjunction with undifferentiated hNPCs. In culture, FSP cells exhibited neuronal electrophysiological properties. However, recordings from GABAergic hNPCs revealed limited ionic conductances and an inability to fire action potentials. Despite this, they were almost as efficacious as FSP cells in inducing functional recovery following transplantation, suggesting that such recovery may have been mediated by secretion of GABA rather than by functional integration into the host. Thus, restoration of dopaminergic activity to the striatum in concert with inhibition of the STN and SN by GABAergic grafts may be beneficial for improving clinical outcomes in patients with Parkinson's disease and potential clinical application of this strategy may be enhanced by the use of differentiated hNPCs.

Notice en format standard (ISO 2709)

Pour connaître la documentation sur le format Inist Standard.

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C01	`01`		`ENG`	@0 The current transplantation paradigm for Parkinson's disease that places foetal dopaminergic cells in the striatum neither normalizes neuronal activity in basal ganglia structures such as the substantia nigra (SN) and subthalamic nucleus (STN) nor leads to complete functional recovery. It was hypothesized that restoration of parkinsonian deficits requires inhibition of the pathological overactivity of the STN and SN in addition to restoration of dopaminergic activity in the striatum. To achieve inhibition, a multitargeted basal ganglia transplantation strategy using GABAergic cells derived from either foetal striatal primordia (FSP) cells or human neural precursor cells (hNPCs) expanded in suspension bioreactors was investigated. In hemiparkinsonian rats, transplantation of foetal rat dopaminergic cells in the striatum in conjunction with GABAergic grafts in the STN and/or SN promoted significant improvement in forelimb akinesia and motor function compared to transplantation of intrastriatal dopaminergic grafts alone or in conjunction with undifferentiated hNPCs. In culture, FSP cells exhibited neuronal electrophysiological properties. However, recordings from GABAergic hNPCs revealed limited ionic conductances and an inability to fire action potentials. Despite this, they were almost as efficacious as FSP cells in inducing functional recovery following transplantation, suggesting that such recovery may have been mediated by secretion of GABA rather than by functional integration into the host. Thus, restoration of dopaminergic activity to the striatum in concert with inhibition of the STN and SN by GABAergic grafts may be beneficial for improving clinical outcomes in patients with Parkinson's disease and potential clinical application of this strategy may be enhanced by the use of differentiated hNPCs.
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Format Inist (serveur)

NO :	PASCAL 08-0387596 INIST
ET :	A multitarget basal ganglia dopaminergic and GABAergic transplantation strategy enhances behavioural recovery in parkinsonian rats
AU :	MUKHIDA (K.); HONG (M.); MILES (G. B.); PHILLIPS (T.); BAGHBADERANI (B. A.); MCLEOD (M.); KOBAYASHI (N.); SEN (A.); BEHIE (L. A.); BROWNSTONE (R. M.); MENDEZ (I.)
AF :	Cell Restoration Laboratory, Dalhousie University/Halifax, Nova Scotia/Canada (1 aut., 2 aut., 4 aut., 6 aut., 7 aut., 11 aut.); Motor Control Laboratory, Departments of Anatomy & Neurobiology and Surgery (Neurosurgery), Dalhousie University/Halifax, Nova Scotia/Canada (3 aut., 10 aut.); Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary/Calgary, Alberta/Canada (5 aut., 8 aut., 9 aut.)
DT :	Publication en série; Niveau analytique
SO :	Brain; ISSN 0006-8950; Royaume-Uni; Da. 2008; Vol. 131; No. p. 8; Pp. 2106-2126; Bibl. 3 p.
LA :	Anglais
EA :	The current transplantation paradigm for Parkinson's disease that places foetal dopaminergic cells in the striatum neither normalizes neuronal activity in basal ganglia structures such as the substantia nigra (SN) and subthalamic nucleus (STN) nor leads to complete functional recovery. It was hypothesized that restoration of parkinsonian deficits requires inhibition of the pathological overactivity of the STN and SN in addition to restoration of dopaminergic activity in the striatum. To achieve inhibition, a multitargeted basal ganglia transplantation strategy using GABAergic cells derived from either foetal striatal primordia (FSP) cells or human neural precursor cells (hNPCs) expanded in suspension bioreactors was investigated. In hemiparkinsonian rats, transplantation of foetal rat dopaminergic cells in the striatum in conjunction with GABAergic grafts in the STN and/or SN promoted significant improvement in forelimb akinesia and motor function compared to transplantation of intrastriatal dopaminergic grafts alone or in conjunction with undifferentiated hNPCs. In culture, FSP cells exhibited neuronal electrophysiological properties. However, recordings from GABAergic hNPCs revealed limited ionic conductances and an inability to fire action potentials. Despite this, they were almost as efficacious as FSP cells in inducing functional recovery following transplantation, suggesting that such recovery may have been mediated by secretion of GABA rather than by functional integration into the host. Thus, restoration of dopaminergic activity to the striatum in concert with inhibition of the STN and SN by GABAergic grafts may be beneficial for improving clinical outcomes in patients with Parkinson's disease and potential clinical application of this strategy may be enhanced by the use of differentiated hNPCs.
CC :	002B17; 002B25J01
FD :	Maladie de Parkinson; Pathologie du système nerveux; Noyau gris central; Transplantation; Stratégie; Récupération; Animal; Rat; Noyau sousthalamique; GABA
FG :	Rodentia; Mammalia; Vertebrata; Encéphale; Système nerveux central; Pathologie de l'encéphale; Syndrome extrapyramidal; Maladie dégénérative; Pathologie du système nerveux central; Neurotransmetteur
ED :	Parkinson disease; Nervous system diseases; Basal ganglion; Transplantation; Strategy; Recovery; Animal; Rat; Subthalamic nucleus; GABA
EG :	Rodentia; Mammalia; Vertebrata; Encephalon; Central nervous system; Cerebral disorder; Extrapyramidal syndrome; Degenerative disease; Central nervous system disease; Neurotransmitter
SD :	Parkinson enfermedad; Sistema nervioso patología; Núcleo basal; Trasplantación; Estrategia; Recuperación; Animal; Rata; Núcleo subtalámico; GABA
LO :	INIST-998.354000196455150130
ID :	08-0387596

Links to Exploration step

Pascal:08-0387596

Le document en format XML

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<front><div type="abstract" xml:lang="en">The current transplantation paradigm for Parkinson's disease that places foetal dopaminergic cells in the striatum neither normalizes neuronal activity in basal ganglia structures such as the substantia nigra (SN) and subthalamic nucleus (STN) nor leads to complete functional recovery. It was hypothesized that restoration of parkinsonian deficits requires inhibition of the pathological overactivity of the STN and SN in addition to restoration of dopaminergic activity in the striatum. To achieve inhibition, a multitargeted basal ganglia transplantation strategy using GABAergic cells derived from either foetal striatal primordia (FSP) cells or human neural precursor cells (hNPCs) expanded in suspension bioreactors was investigated. In hemiparkinsonian rats, transplantation of foetal rat dopaminergic cells in the striatum in conjunction with GABAergic grafts in the STN and/or SN promoted significant improvement in forelimb akinesia and motor function compared to transplantation of intrastriatal dopaminergic grafts alone or in conjunction with undifferentiated hNPCs. In culture, FSP cells exhibited neuronal electrophysiological properties. However, recordings from GABAergic hNPCs revealed limited ionic conductances and an inability to fire action potentials. Despite this, they were almost as efficacious as FSP cells in inducing functional recovery following transplantation, suggesting that such recovery may have been mediated by secretion of GABA rather than by functional integration into the host. Thus, restoration of dopaminergic activity to the striatum in concert with inhibition of the STN and SN by GABAergic grafts may be beneficial for improving clinical outcomes in patients with Parkinson's disease and potential clinical application of this strategy may be enhanced by the use of differentiated hNPCs.</div>
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<fC01 i1="01" l="ENG"><s0>The current transplantation paradigm for Parkinson's disease that places foetal dopaminergic cells in the striatum neither normalizes neuronal activity in basal ganglia structures such as the substantia nigra (SN) and subthalamic nucleus (STN) nor leads to complete functional recovery. It was hypothesized that restoration of parkinsonian deficits requires inhibition of the pathological overactivity of the STN and SN in addition to restoration of dopaminergic activity in the striatum. To achieve inhibition, a multitargeted basal ganglia transplantation strategy using GABAergic cells derived from either foetal striatal primordia (FSP) cells or human neural precursor cells (hNPCs) expanded in suspension bioreactors was investigated. In hemiparkinsonian rats, transplantation of foetal rat dopaminergic cells in the striatum in conjunction with GABAergic grafts in the STN and/or SN promoted significant improvement in forelimb akinesia and motor function compared to transplantation of intrastriatal dopaminergic grafts alone or in conjunction with undifferentiated hNPCs. In culture, FSP cells exhibited neuronal electrophysiological properties. However, recordings from GABAergic hNPCs revealed limited ionic conductances and an inability to fire action potentials. Despite this, they were almost as efficacious as FSP cells in inducing functional recovery following transplantation, suggesting that such recovery may have been mediated by secretion of GABA rather than by functional integration into the host. Thus, restoration of dopaminergic activity to the striatum in concert with inhibition of the STN and SN by GABAergic grafts may be beneficial for improving clinical outcomes in patients with Parkinson's disease and potential clinical application of this strategy may be enhanced by the use of differentiated hNPCs.</s0>
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<ET>A multitarget basal ganglia dopaminergic and GABAergic transplantation strategy enhances behavioural recovery in parkinsonian rats</ET>
<AU>MUKHIDA (K.); HONG (M.); MILES (G. B.); PHILLIPS (T.); BAGHBADERANI (B. A.); MCLEOD (M.); KOBAYASHI (N.); SEN (A.); BEHIE (L. A.); BROWNSTONE (R. M.); MENDEZ (I.)</AU>
<AF>Cell Restoration Laboratory, Dalhousie University/Halifax, Nova Scotia/Canada (1 aut., 2 aut., 4 aut., 6 aut., 7 aut., 11 aut.); Motor Control Laboratory, Departments of Anatomy & Neurobiology and Surgery (Neurosurgery), Dalhousie University/Halifax, Nova Scotia/Canada (3 aut., 10 aut.); Pharmaceutical Production Research Facility, Schulich School of Engineering, University of Calgary/Calgary, Alberta/Canada (5 aut., 8 aut., 9 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Brain; ISSN 0006-8950; Royaume-Uni; Da. 2008; Vol. 131; No. p. 8; Pp. 2106-2126; Bibl. 3 p.</SO>
<LA>Anglais</LA>
<EA>The current transplantation paradigm for Parkinson's disease that places foetal dopaminergic cells in the striatum neither normalizes neuronal activity in basal ganglia structures such as the substantia nigra (SN) and subthalamic nucleus (STN) nor leads to complete functional recovery. It was hypothesized that restoration of parkinsonian deficits requires inhibition of the pathological overactivity of the STN and SN in addition to restoration of dopaminergic activity in the striatum. To achieve inhibition, a multitargeted basal ganglia transplantation strategy using GABAergic cells derived from either foetal striatal primordia (FSP) cells or human neural precursor cells (hNPCs) expanded in suspension bioreactors was investigated. In hemiparkinsonian rats, transplantation of foetal rat dopaminergic cells in the striatum in conjunction with GABAergic grafts in the STN and/or SN promoted significant improvement in forelimb akinesia and motor function compared to transplantation of intrastriatal dopaminergic grafts alone or in conjunction with undifferentiated hNPCs. In culture, FSP cells exhibited neuronal electrophysiological properties. However, recordings from GABAergic hNPCs revealed limited ionic conductances and an inability to fire action potentials. Despite this, they were almost as efficacious as FSP cells in inducing functional recovery following transplantation, suggesting that such recovery may have been mediated by secretion of GABA rather than by functional integration into the host. Thus, restoration of dopaminergic activity to the striatum in concert with inhibition of the STN and SN by GABAergic grafts may be beneficial for improving clinical outcomes in patients with Parkinson's disease and potential clinical application of this strategy may be enhanced by the use of differentiated hNPCs.</EA>
<CC>002B17; 002B25J01</CC>
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<FG>Rodentia; Mammalia; Vertebrata; Encéphale; Système nerveux central; Pathologie de l'encéphale; Syndrome extrapyramidal; Maladie dégénérative; Pathologie du   système nerveux central; Neurotransmetteur</FG>
<ED>Parkinson disease; Nervous system diseases; Basal ganglion; Transplantation; Strategy; Recovery; Animal; Rat; Subthalamic nucleus; GABA</ED>
<EG>Rodentia; Mammalia; Vertebrata; Encephalon; Central nervous system; Cerebral disorder; Extrapyramidal syndrome; Degenerative disease; Central nervous system disease; Neurotransmitter</EG>
<SD>Parkinson enfermedad; Sistema nervioso patología; Núcleo basal; Trasplantación; Estrategia; Recuperación; Animal; Rata; Núcleo subtalámico; GABA</SD>
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	La maladie de Parkinson au Canada (serveur d'exploration)
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La maladie de Parkinson au Canada (serveur d'exploration)

A multitarget basal ganglia dopaminergic and GABAergic transplantation strategy enhances behavioural recovery in parkinsonian rats

A multitarget basal ganglia dopaminergic and GABAergic transplantation strategy enhances behavioural recovery in parkinsonian rats

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