Chronic quinolinic acid lesions in rats closely resemble Huntington's disease
- PMID: 1710657
- PMCID: PMC6575424
- DOI: 10.1523/JNEUROSCI.11-06-01649.1991
Chronic quinolinic acid lesions in rats closely resemble Huntington's disease
Abstract
We previously found a relative sparing of somatostatin and neuropeptide Y neurons 1 week after producing striatal lesions with NMDA receptor agonists. These results are similar to postmortem findings in Huntington's disease (HD), though in this illness there are two- to threefold increases in striatal somatostatin and neuropeptide Y concentrations, which may be due to striatal atrophy. In the present study, we examined the effects of striatal excitotoxin lesions at 6 months and 1 yr, because these lesions exhibit striatal shrinkage and atrophy similar to that occurring in HD striatum. At 6 months and 1 yr, lesions with the NMDA receptor agonist quinolinic acid (QA) resulted in significant increases (up to twofold) in concentrations of somatostatin and neuropeptide Y immunoreactivity, while concentrations of GABA, substance P immunoreactivity, and ChAT activity were significantly reduced. In contrast, somatostatin and neuropeptide Y concentrations did not increase 6 months after kainic acid (KA) or alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) lesions. At both 6 months and 1 yr, QA lesions showed striking sparing of NADPH-diaphorase neurons as compared with both AMPA and KA lesions, neither of which showed preferential sparing of these neurons. Long-term QA lesions also resulted in significant increases in concentrations of both 5-HT and 5-hydroxyindoleacetic acid (HIAA), similar to findings in HD. Chronic QA lesions therefore closely resemble the neurochemical features of HD, because they result in increases in somatostatin and neuropeptide Y and in 5-HT and HIAA. These findings strengthen the possibility that an NMDA receptor-mediated excitotoxic process could play a role in the pathogenesis of HD.
Similar articles
-
Differential sparing of somatostatin-neuropeptide Y and cholinergic neurons following striatal excitotoxin lesions.Synapse. 1989;3(1):38-47. doi: 10.1002/syn.890030106. Synapse. 1989. PMID: 2563916
-
Neurochemical characterization of excitotoxin lesions in the cerebral cortex.J Neurosci. 1991 Jan;11(1):147-58. doi: 10.1523/JNEUROSCI.11-01-00147.1991. J Neurosci. 1991. PMID: 1670782 Free PMC article.
-
Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid.Nature. 1986 May 8-14;321(6066):168-71. doi: 10.1038/321168a0. Nature. 1986. PMID: 2422561
-
Chemical anatomy of striatal interneurons in normal individuals and in patients with Huntington's disease.Brain Res Brain Res Rev. 2000 Nov;34(1-2):80-101. doi: 10.1016/s0165-0173(00)00039-4. Brain Res Brain Res Rev. 2000. PMID: 11086188 Review.
-
Glutamate and Huntington's disease.Med J Aust. 1981 Oct 31;2(9):460-5. doi: 10.5694/j.1326-5377.1981.tb112939.x. Med J Aust. 1981. PMID: 6119604 Review.
Cited by
-
Regenerative Approaches in Huntington's Disease: From Mechanistic Insights to Therapeutic Protocols.Front Neurosci. 2018 Nov 2;12:800. doi: 10.3389/fnins.2018.00800. eCollection 2018. Front Neurosci. 2018. PMID: 30450032 Free PMC article. Review.
-
Purification and molecular cloning of rat 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase.Biochem J. 2002 Feb 1;361(Pt 3):567-75. doi: 10.1042/0264-6021:3610567. Biochem J. 2002. PMID: 11802786 Free PMC article.
-
Cell-Autonomous and Non-cell-Autonomous Pathogenic Mechanisms in Huntington's Disease: Insights from In Vitro and In Vivo Models.Neurotherapeutics. 2019 Oct;16(4):957-978. doi: 10.1007/s13311-019-00782-9. Neurotherapeutics. 2019. PMID: 31529216 Free PMC article. Review.
-
G-Protein-Coupled Receptors in CNS: A Potential Therapeutic Target for Intervention in Neurodegenerative Disorders and Associated Cognitive Deficits.Cells. 2020 Feb 23;9(2):506. doi: 10.3390/cells9020506. Cells. 2020. PMID: 32102186 Free PMC article. Review.
-
Purinergic Receptors in Neurological Diseases With Motor Symptoms: Targets for Therapy.Front Pharmacol. 2018 Apr 10;9:325. doi: 10.3389/fphar.2018.00325. eCollection 2018. Front Pharmacol. 2018. PMID: 29692728 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical