Activation of the subthalamic nucleus and pedunculopontine tegmentum: Does it affect dopamine levels in the Substantia nigra, Nucleus accumbens and striatum?

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dc.contributor.authorJaffer A.
dc.contributor.authorVan der Spuy G.D.
dc.contributor.authorRussell V.A.
dc.contributor.authorMintz M.
dc.contributor.authorTaljaard J.J.F.
dc.contributor.authorJaffer A.
dc.contributor.authorVan der Spuy G.D.
dc.contributor.authorRussell V.A.
dc.contributor.authorMintz M.
dc.contributor.authorTaljaard J.J.F.
dc.date.accessioned2011-05-15T16:17:29Z
dc.date.accessioned2011-05-15T16:17:29Z
dc.date.available2011-05-15T16:17:29Z
dc.date.available2011-05-15T16:17:29Z
dc.date.issued1995
dc.date.issued1995
dc.description.abstractParkinson's disease is a neurodegenerative disorder, of which the most prominent morphological feature is the progressive loss of dopaminergic nigrostriatal neurons. Increased glutamatergic transmission in the basal ganglia has been implicated in the pathophysiology of Parkinson's disease (PD). This study investigated whether death of substantia nigra (SN) dopaminergic neurons could be caused by the hyperactivity of afferent pathways resulting in the release of a toxic dose of excitatory amino acids in the SN. Twice-daily unilateral stimulation of the subthalamic nucleus (STN) for 21 days, using two different pulse frequencies and current strengths, significantly increased amphetamine-induced rotation, whereas sham stimulated rats showed significantly reduced rotation. Striatal and SN dopamine (DA) levels were unaffected when compared to naive and sham stimulated rats. However, levels of the DA metabolite, homovanillic acid (HVA), were significantly higher in the ipsilateral anterior striata of rats that had been stimulated at high frequency (100 Hz) and low current (100 μA) as compared to sham treated animals. Stimulation of the pedunculopontine tegmentum (PPT), using a single kainic acid injection, did not affect DA concentration in the ipsilateral striatum and nucleus accumbens when compared to sham-treated rats. DA levels in the contralateral striatum and nucleus accumbens of lesioned rats were significantly higher than ipsilateral levels. DOPAC/DA ratios were lower in the contralateral striatum and nucleus accumbens, suggesting decreased DA turnover. Glutamic acid decarboxylase activity was significantly higher in the ipsilateral than the contralateral SN. The physical manifestations of PD require a large reduction in caudate and putamen DA levels and no such depletion was measured in this study. These results, therefore, do not support the hypothesis that Parkinson's disease may result from an overstimulation of substantia nigral DA neurons by glutamate afferents originating from the STN or PPT.
dc.description.abstractParkinson's disease is a neurodegenerative disorder, of which the most prominent morphological feature is the progressive loss of dopaminergic nigrostriatal neurons. Increased glutamatergic transmission in the basal ganglia has been implicated in the pathophysiology of Parkinson's disease (PD). This study investigated whether death of substantia nigra (SN) dopaminergic neurons could be caused by the hyperactivity of afferent pathways resulting in the release of a toxic dose of excitatory amino acids in the SN. Twice-daily unilateral stimulation of the subthalamic nucleus (STN) for 21 days, using two different pulse frequencies and current strengths, significantly increased amphetamine-induced rotation, whereas sham stimulated rats showed significantly reduced rotation. Striatal and SN dopamine (DA) levels were unaffected when compared to naive and sham stimulated rats. However, levels of the DA metabolite, homovanillic acid (HVA), were significantly higher in the ipsilateral anterior striata of rats that had been stimulated at high frequency (100 Hz) and low current (100 μA) as compared to sham treated animals. Stimulation of the pedunculopontine tegmentum (PPT), using a single kainic acid injection, did not affect DA concentration in the ipsilateral striatum and nucleus accumbens when compared to sham-treated rats. DA levels in the contralateral striatum and nucleus accumbens of lesioned rats were significantly higher than ipsilateral levels. DOPAC/DA ratios were lower in the contralateral striatum and nucleus accumbens, suggesting decreased DA turnover. Glutamic acid decarboxylase activity was significantly higher in the ipsilateral than the contralateral SN. The physical manifestations of PD require a large reduction in caudate and putamen DA levels and no such depletion was measured in this study. These results, therefore, do not support the hypothesis that Parkinson's disease may result from an overstimulation of substantia nigral DA neurons by glutamate afferents originating from the STN or PPT.
dc.description.versionArticle
dc.description.versionArticle
dc.identifier.citationNeurodegeneration
dc.identifier.citation4
dc.identifier.citation2
dc.identifier.citationNeurodegeneration
dc.identifier.citation4
dc.identifier.citation2
dc.identifier.issn10558330
dc.identifier.issn10558330
dc.identifier.other10.1006/neur.1995.0017
dc.identifier.other10.1006/neur.1995.0017
dc.identifier.urihttp://hdl.handle.net/10019.1/14237
dc.identifier.urihttp://hdl.handle.net/10019.1/14237
dc.subjectdopamine; excitatory amino acid; glutamate decarboxylase; homovanillic acid; kainic acid; animal experiment; animal model; animal tissue; article; controlled study; corpus striatum; dopamine metabolism; dopaminergic nerve cell; electrostimulation; enzyme activity; male; nonhuman; nucleus accumbens; parkinson disease; pons; priority journal; rat; sensory nerve; substantia nigra; subthalamic nucleus; tegmentum; 3,4-Dihydroxyphenylacetic Acid; Analysis of Variance; Animal; Corpus Striatum; Dopamine; Electric Stimulation; Glutamate Decarboxylase; Homovanillic Acid; Male; Neurons; Nucleus Accumbens; Rats; Rats, Wistar; Substantia Nigra; Support, Non-U.S. Gov't; Tegmentum Mesencephali; Thalamic Nuclei
dc.subjectdopamine
dc.subjectexcitatory amino acid
dc.subjectglutamate decarboxylase
dc.subjecthomovanillic acid
dc.subjectkainic acid
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectarticle
dc.subjectcontrolled study
dc.subjectcorpus striatum
dc.subjectdopamine metabolism
dc.subjectdopaminergic nerve cell
dc.subjectelectrostimulation
dc.subjectenzyme activity
dc.subjectmale
dc.subjectnonhuman
dc.subjectnucleus accumbens
dc.subjectparkinson disease
dc.subjectpons
dc.subjectpriority journal
dc.subjectrat
dc.subjectsensory nerve
dc.subjectsubstantia nigra
dc.subjectsubthalamic nucleus
dc.subjecttegmentum
dc.subject3,4-Dihydroxyphenylacetic Acid
dc.subjectAnalysis of Variance
dc.subjectAnimal
dc.subjectCorpus Striatum
dc.subjectDopamine
dc.subjectElectric Stimulation
dc.subjectGlutamate Decarboxylase
dc.subjectHomovanillic Acid
dc.subjectMale
dc.subjectNeurons
dc.subjectNucleus Accumbens
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectSubstantia Nigra
dc.subjectSupport, Non-U.S. Gov't
dc.subjectTegmentum Mesencephali
dc.subjectThalamic Nuclei
dc.titleActivation of the subthalamic nucleus and pedunculopontine tegmentum: Does it affect dopamine levels in the Substantia nigra, Nucleus accumbens and striatum?
dc.titleActivation of the subthalamic nucleus and pedunculopontine tegmentum: Does it affect dopamine levels in the Substantia nigra, Nucleus accumbens and striatum?
dc.typeArticle
dc.typeArticle
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