The role of striatopallidal neurones utilizing gamma-aminobutyric acid in the pathophysiology of MPTP-induced parkinsonism in the primate: evidence from [3H]flunitrazepam autoradiography

Robertson, R. G. H.; Clarke, Charlie; Boyce, S.; Sambrook, M.A.; Crossman, Alan R.

doi:10.1016/0006-8993(90)90762-z

Cited by 69 publications

(24 citation statements)

References 51 publications

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“…In nonhuman primates, administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (M P TP), either systemically or by intracarotid inf usion, has resulted in marked increases in preproenkephalin (PPE) gene expression, particularly in the dorsolateral sensorimotor striatal territories (Augood et al, 1989;Asselin et al, 1994;Herrero et al, 1995). These data, as well as findings from a number of other studies (Voorn et al, 1987;Robertson et al, 1990;Sivam and Krause, 1990), support the proposal that DA exerts a tonic inhibitory control, mediated via D2 receptors, over enkephalin-containing striatopallidal output neurons.…”

Section: Abstract: Enkephalin; Striatum; Parkinsonism; Dopamine; Monsupporting

confidence: 62%

Striatal Preproenkephalin Gene Expression Is Upregulated in Acute but Not Chronic Parkinsonian Monkeys: Implications for the Contribution of the Indirect Striatopallidal Circuit to Parkinsonian Symptomatology

1999

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This study examined the extent of striatal dopamine (DA) denervation and coincident expression of preproenkephalin (PPE) mRNA in monkeys made parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. Some animals (n ϭ 4) became moderately parkinsonian after receiving large doses of MPTP over short periods of time and were symptomatic for only a short period of time (1-3 months; acute parkinsonian group). Other animals became moderately parkinsonian after receiving either escalating doses of MPTP over long periods (4-6 months; n ϭ 5) or a high dose of MPTP over a short period (Ͻ1 month; n ϭ 1) and remained symptomatic for an extended period (Ͼ8 months; chronic parkinsonian group). Despite similar symptomatology and similar degrees of striatal DA denervation at the time of their deaths, only acute parkinsonian animals had significantly increased PPE expression in sensorimotor striatal regions. PPE expression in chronic parkinsonian animals was either not changed or significantly decreased in most striatal regions. These findings suggest that the duration and not the extent of striatal DA denervation is a critical factor in modulating changes in striatal PPE expression. Furthermore, these results question the role of increased activity in the enkephalin-containing indirect striatopallidal pathway in the expression of parkinsonian symptoms.

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Section: Abstract: Enkephalin; Striatum; Parkinsonism; Dopamine; Monsupporting

confidence: 62%

Striatal Preproenkephalin Gene Expression Is Upregulated in Acute but Not Chronic Parkinsonian Monkeys: Implications for the Contribution of the Indirect Striatopallidal Circuit to Parkinsonian Symptomatology

1999

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“…Changes in pallidal BZ binding sites were also noticed in animal models of PD. MPTP-treated monkeys show an increased level of GABA/BZ binding in the GPi which could be reversed by treatment with the long acting D2 receptor agonist, cabergoline, but not by the Dl receptor agonist, SKF 82958 (Robertson et al, 1990;Calon et al, 1995Calon et al, , 1999. In contrast, the density of GABA/BZ binding sites is decreased in GPe after MPTP treatment (Griffiths et al, 1990;Robertson et al, 1990).…”

Section: Gaba-a Receptorsmentioning

confidence: 99%

“…MPTP-treated monkeys show an increased level of GABA/BZ binding in the GPi which could be reversed by treatment with the long acting D2 receptor agonist, cabergoline, but not by the Dl receptor agonist, SKF 82958 (Robertson et al, 1990;Calon et al, 1995Calon et al, , 1999. In contrast, the density of GABA/BZ binding sites is decreased in GPe after MPTP treatment (Griffiths et al, 1990;Robertson et al, 1990). This up-and downregulation of GABA-A receptors in GPi and GPe, respectively, is consistent with the current functional model of basal ganglia circuitry which suggests that the activity of the "so-called" direct striato-GPi pathway is decreased in PD whereas the activity of the "indirect" striato-GPe projection is increased (Albin et al, 1989;.…”

Section: Gaba-a Receptorsmentioning

confidence: 99%

Kainate Receptors in the Striatum: Implications for Excitoxicity in Huntington's Disease

Smith¹

2002

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Section: Gab A-a Receptorsmentioning

confidence: 99%

“…MPTP-treated monkeys show an increased level of GABA/BZ binding in the GPi which could be reversed by treatment with the long acting D2 receptor agonist, cabergoline, but not by the Dl receptor agonist, SKF 82958 (Robertson et al, 1990;Calon et al, 1995;. In contrast, the density of GABA/BZ binding sites is decreased in GPe after MPTP treatment (Griffiths et al, 1990;Robertson et al,' 1990). This up-and downregulation of GABA-A receptors in GPi and GPe, respectively, is consistent with the current functional model of basal ganglia circuitry which suggests that the activity of the "so-called" direct striato-GPi pathway is decreased in Parkinson's disease whereas the activity of the "indirect" striato-GPe projection is increased (Albin et al, 1989;DeLong, 1990).…”

Section: Gab A-a Receptorsmentioning

confidence: 99%

Kainate Receptors in the Striatum: Implications for Excitotoxicity in Huntington's Disease

Smith¹

2003

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and yolands@rmy.emory.edu Huntington's disease (HD) is a neurodegenerative condition characterized by a loss of projection neurons in the striatum. Although various hypotheses have been proposed to explain the mechanisms that underlie the striatal neuronal death, excitotoxicity still deserves major interest. Recent findings indicate that changes in the genotype of the kainate receptor subunit, GluR6, are associated with variation in the age of onset of HD, which implicates the kainate receptors in the pathogenesis of HD. The rationale of this project is that pre-synaptic kainate receptors control the release of glutamate from cortical or thalamic terminals, and that an abnormal regulation of these receptors is involved in the death of striatal neurons in HD. We, therefore, propose to use state-of-the-art electron microscope techniques to test a series of hypotheses that will help to elucidate the localization and understand better the role of kainate receptors in the primate striatum. The results of these studies will provide a strong basis for studying the potential mechanisms by which these receptors participate in the death of striatofugal neurons in HD. Moreover, they will help the development of novel therapeutic strategies aimed at targeting presynaptic kainate receptors in HD and other basal ganglia disorders. PERFORMING ORGANIZATION NAME(S) AND ÄDDRESS(ES)Emory SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES)U SUBJECT TERMS INTRODUCTION:Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by the death of striatal neurons. Chorea is the most common involuntary movement in patients who suffer of HD. This could be combined with cognitive and memory deficits at a later stage of the disease. The HD mutation was identified in 1993 as an unstable expansion of CAG (trinucleotide) repeats on the gene which encodes the protein "Huntingtin" on chromosome 4. In more than 60% of HD patients, there is a high degree of inverse correlation between the number of CAG repeats and the age of onset of the disease or degree of striatal degeneration (Vonsatell and DiFiglia, 1998). However, about 15% of the HD cases of which the age of onset cannot be explained by the CAG repeats, were found to have mutations in the gene encoding the GluR6 subunit of the glutamatergic kainate receptor (Rubinztein et al., 1997;MacDonald et al., 1999) which highlight the importance of those receptors in the pathogene...

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The role of striatopallidal neurones utilizing gamma-aminobutyric acid in the pathophysiology of MPTP-induced parkinsonism in the primate: evidence from [3H]flunitrazepam autoradiography

Cited by 69 publications

References 51 publications

Striatal Preproenkephalin Gene Expression Is Upregulated in Acute but Not Chronic Parkinsonian Monkeys: Implications for the Contribution of the Indirect Striatopallidal Circuit to Parkinsonian Symptomatology

Striatal Preproenkephalin Gene Expression Is Upregulated in Acute but Not Chronic Parkinsonian Monkeys: Implications for the Contribution of the Indirect Striatopallidal Circuit to Parkinsonian Symptomatology

Kainate Receptors in the Striatum: Implications for Excitoxicity in Huntington's Disease

Kainate Receptors in the Striatum: Implications for Excitotoxicity in Huntington's Disease

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