Kainate-induced degeneration of neostriatal neurons: dependency upon corticostriatal tract

McGeer, Edith G.; McGeer, Patrick L.; Singh, Kartar

doi:10.1016/0006-8993(78)90941-1

Cited by 317 publications

(65 citation statements)

References 6 publications

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“…Complementary evidence has been obtained by other groups to suggest that corticostriate fibres also release an amino acid, probably glutamate (Spencer, 1976;Divac, Fonnum & Storm-Mathisen, 1977;McGeer, McGeer & Singh, 1978). It is therefore possible that all cortical efferent excitatory axons utilize an amino acid transmitter.…”

Section: Introductionsupporting

confidence: 57%

Amino Acids as Neurotransmitters of Corticofugal Neurones in the Rat: A Comparison of Glutamate and Aspartate

Stone

1979

British J Pharmacology

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Section: Introductionsupporting

confidence: 57%

Amino Acids as Neurotransmitters of Corticofugal Neurones in the Rat: A Comparison of Glutamate and Aspartate

Stone

1979

British J Pharmacology

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“…Striatal lesions produced by quinolinic acid, NMDA, and kainic acid are all attenuated after lesions of the nigrostriatal dopaminergic pathway (McGeer et al, 1978;Biziere and Coyle, 1979;Chapman et al, 1989;Buisson et al, 1991). Striatal lesions produced by the mitochondrial toxins malonate and 3-nitropropionic acid are also both markedly attenuated by lesions of the nigrostriatal pathway (Maragos et al, 1998;Reynolds et al, 1998;Jakel and Maragos, 2000;Moy et al, 2000;Calabresi et al, 2001).…”

Section: Discussionmentioning

confidence: 98%

“…It is well established that striatal excitotoxic lesions depend on corticostriatal glutamatergic inputs (McGeer et al, 1978;Biziere and Coyle, 1979). There is also a substantial body of evidence indicating that striatal excitotoxic lesions are dependent on dopaminergic inputs from the substantia nigra (McGeer et al, 1978;Biziere and Coyle, 1979;Meldrum et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…There is also a substantial body of evidence indicating that striatal excitotoxic lesions are dependent on dopaminergic inputs from the substantia nigra (McGeer et al, 1978;Biziere and Coyle, 1979;Meldrum et al, 2001). Nigrostriatal dopaminergic neurotransmission is altered in HD based on early and dramatic changes in related receptors and may contribute to striatal vulnerability in HD.…”

Section: Introductionmentioning

confidence: 99%

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Neuroprotective Effects of Synaptic Modulation in Huntington's Disease R6/2 Mice

Stack¹,

Dedeoglu²,

Smith³

et al. 2007

J. Neurosci.

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Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder in which the neostriatum degenerates early and most severely, with involvement of other brain regions. There is significant evidence that excitotoxicity may play a role in striatal degeneration through altered afferent corticostriatal and nigrostriatal projections that may modulate synaptically released striatal glutamate. Glutamate is a central tenant in provoking excitotoxic cell death in striatal neurons already weakened by the collective molecular events occurring in HD. In addition, transcriptional suppression of trophic factors occurs in human and transgenic mouse models of HD, suggesting that a loss of trophic support might contribute to degeneration. Since anti-glutamate approaches have been effective in improving disease phenotype in HD mice, we examined whether deafferentation of the corticostriatal and nigrostriatal pathways may mitigate striatal stress and neurodegeneration. Both surgical and chemical lesions of the corticostriatal and nigrostriatal pathways, respectively, improved the behavioral, neuropathological, and biochemical phenotype in R6/2 transgenic mice and extended survival. Decortication ameliorated hindlimb clasping, striatal neuron atrophy, and huntingtin-positive aggregates, improved N-acetyl aspartate/creatine levels, reduced oxidative stress, and significantly lowered striatal glutamate levels. In addition, 6-hydroxydopamine lesioned mice showed extended survival along with a significant reduction in striatal glutamate. These results suggest that synaptic stress is likely to contribute to neurodegeneration in HD, whereas transsynaptic trophic influences may not be as salient. Thus, modulation of synaptic influences continues to have therapeutic potential in HD.

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“…Injections of kainic acid into the striatum have, indeed, been known to cause cell death in striatal projection neurons, but to have no such effect on axons crossing or terminating in the area (Coyle and Schwarcz, 1976;McGeer and McGeer, 1976). The fact that these neurotoxic effects of kainate in the striatum are attenuated after decortication (McGeer et al, 1978;Biziere and Coyle, 1979), implies that these effects are mediated via cortical terminal glutamate release. In line with these observations, recent findings from our laboratory have demonstrated the presence of KAR immunoreactivity on glutamatergic nerve terminals in the monkey striatum (Charara et al, 1999).…”

Section: Abstract: Huntington's Disease; Excitotoxicity; Presynapticmentioning

confidence: 99%

Subcellular and Subsynaptic Localization of Presynaptic and Postsynaptic Kainate Receptor Subunits in the Monkey Striatum

et al. 2001

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The localization and functions of kainate receptors (KARs) in the CNS are still poorly known. In the striatum, GluR6/7 and KA2 immunoreactivity is expressed presynaptically in a subpopulation of glutamatergic terminals and postsynaptically in dendrites and spines. The goal of this study was to further characterize the subcellular and subsynaptic localization of kainate receptor subunits in the monkey striatum. Immunoperoxidase data reveal that the relative abundance of GluR6/7-and KA2-immunoreactive terminals is homogeneous throughout the striatum irrespective of the differential degree of striatal degeneration in Huntington's disease. Pre-embedding and post-embedding immunogold data indicate that Ͼ70% of the presynaptic or postsynaptic GluR6/7 and KA2 labeling is expressed intracellularly. In material stained with the post-embedding immunogold method, approximately one-third of plasma membrane-bound gold particles labeling in axon terminals and spines is associated with asymmetric synapses, thereby representing synaptic kainate receptor subunits. On the other hand, Ͼ60% of the plasmamembrane bound labeling is extrasynaptic. Both GluR6/7 and KA2 labeling in glutamatergic terminals often occurs in clusters of gold particles along the membrane of large vesicular organelles located at various distances from the presynaptic grid. Anterograde labeling from the primary motor cortex or the centromedian thalamic nucleus indicate that both corticostriatal and thalamostriatal terminals express presynaptic GluR6/7 and KA2 immunoreactivity in the postcommissural putamen. In conclusion, these data demonstrate that kainate receptors in the striatum display a pattern of subcellular distribution different from other ionotropic glutamate receptor subtypes, but consistent with their metabotropic-like functions recently shown in the hippocampus.

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Kainate-induced degeneration of neostriatal neurons: dependency upon corticostriatal tract

Cited by 317 publications

References 6 publications

Amino Acids as Neurotransmitters of Corticofugal Neurones in the Rat: A Comparison of Glutamate and Aspartate

Amino Acids as Neurotransmitters of Corticofugal Neurones in the Rat: A Comparison of Glutamate and Aspartate

Neuroprotective Effects of Synaptic Modulation in Huntington's Disease R6/2 Mice

Subcellular and Subsynaptic Localization of Presynaptic and Postsynaptic Kainate Receptor Subunits in the Monkey Striatum

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