Relative survival of striatal projection neurons and interneurons after intrastriatal injection of quinolinic acid in rats

G. Figueredo-Cardenas, K. D. Anderson, Q. Chen, C. L. Veenman, Anton Reiner

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

An excitotoxic process mediated by the NMDA type glutamate receptor may be involved in striatal neuron death in Huntington’s disease (HD). To explore this possibility, we have injected an NMDA-receptor-specific excitotoxin, quinolinic acid (QA), into the striatum in adult rats and 2-4 months postlesion explored the relative patterns of survival for the various different types of striatal projection neurons and interneurons and for the striatal efferent fibers in the different striatal projection areas. The perikarya of specific types of striatal neurons were identified by neurotransmitter immunohistochemical labeling or by retrograde labeling from striatal target areas, while the striatal efferent fiber plexuses were identified by neurotransmitter immunohistochemical labeling. The pattern of survival for the perikarya of each neuron type as a function of distance from the center of the injection site was determined, and the relative survival of each type was compared. For the fibers in target areas, computer-assisted image analysis was used to determine the degree of fiber loss for each projection target. In the study of perikaryal vulnerability, we found that the somatostatin-neuropeptide Y (SS/NPY) interneurons were the most vulnerable to QA and the cholinergic neurons were invulnerable to QA. The perikarya of all projection neuron types (striatopallidal, striatonigral, and striato-entopeduncular) were less vulnerable than the SS/NPY interneurons and more vulnerable than the cholinergic interneurons. Among projection neuron perikarya, there was evidence of differential vulnerability, with striatonigral neurons appearing to be the most vulnerable. Examination of immunolabeled striatal fibers in the striatal target areas indicated that striato-entopeduncular fibers better survived intrastriatal QA than did striatopallidal or striatonigral fibers. The apparent order of vulnerability observed in this study among projection neurons and/or their efferent fiber plexuses and the invulnerability observed in this study of cholinergic interneurons is similar to that observed in HD. The vulnerability of the SS/NPY interneurons to QA is, however, in stark contrast to their invulnerability in HD. The results thus suggest that although the excitotoxin hypothesis of striatal neuron death in HD has merit, QA injections into adult rat striatum do not strictly mimic the outcome in HD. This suggests that either adult rats are not a completely suitable subject for mimicking HD or the HD excitotoxic process does not involve a freely circulating excitotoxin such as QA.

Original languageEnglish (US)
Pages (from-to)37-56
Number of pages20
JournalExperimental Neurology
Volume129
Issue number1
DOIs
StatePublished - Jan 1 1994

Fingerprint

Quinolinic Acid
Corpus Striatum
Interneurons
Huntington Disease
Neurons
Injections
Neuropeptide Y
Neurotoxins
Somatostatin
N-Methyl-D-Aspartate Receptors
Cholinergic Agents
Neurotransmitter Agents
Cholinergic Neurons
Computer-Assisted Image Processing
Glutamate Receptors

All Science Journal Classification (ASJC) codes

  • Neurology
  • Developmental Neuroscience

Cite this

Relative survival of striatal projection neurons and interneurons after intrastriatal injection of quinolinic acid in rats. / Figueredo-Cardenas, G.; Anderson, K. D.; Chen, Q.; Veenman, C. L.; Reiner, Anton.

In: Experimental Neurology, Vol. 129, No. 1, 01.01.1994, p. 37-56.

Research output: Contribution to journalArticle

Figueredo-Cardenas, G. ; Anderson, K. D. ; Chen, Q. ; Veenman, C. L. ; Reiner, Anton. / Relative survival of striatal projection neurons and interneurons after intrastriatal injection of quinolinic acid in rats. In: Experimental Neurology. 1994 ; Vol. 129, No. 1. pp. 37-56.
@article{d5a7f15600994e1392e8fc2a3bc09e8a,
title = "Relative survival of striatal projection neurons and interneurons after intrastriatal injection of quinolinic acid in rats",
abstract = "An excitotoxic process mediated by the NMDA type glutamate receptor may be involved in striatal neuron death in Huntington’s disease (HD). To explore this possibility, we have injected an NMDA-receptor-specific excitotoxin, quinolinic acid (QA), into the striatum in adult rats and 2-4 months postlesion explored the relative patterns of survival for the various different types of striatal projection neurons and interneurons and for the striatal efferent fibers in the different striatal projection areas. The perikarya of specific types of striatal neurons were identified by neurotransmitter immunohistochemical labeling or by retrograde labeling from striatal target areas, while the striatal efferent fiber plexuses were identified by neurotransmitter immunohistochemical labeling. The pattern of survival for the perikarya of each neuron type as a function of distance from the center of the injection site was determined, and the relative survival of each type was compared. For the fibers in target areas, computer-assisted image analysis was used to determine the degree of fiber loss for each projection target. In the study of perikaryal vulnerability, we found that the somatostatin-neuropeptide Y (SS/NPY) interneurons were the most vulnerable to QA and the cholinergic neurons were invulnerable to QA. The perikarya of all projection neuron types (striatopallidal, striatonigral, and striato-entopeduncular) were less vulnerable than the SS/NPY interneurons and more vulnerable than the cholinergic interneurons. Among projection neuron perikarya, there was evidence of differential vulnerability, with striatonigral neurons appearing to be the most vulnerable. Examination of immunolabeled striatal fibers in the striatal target areas indicated that striato-entopeduncular fibers better survived intrastriatal QA than did striatopallidal or striatonigral fibers. The apparent order of vulnerability observed in this study among projection neurons and/or their efferent fiber plexuses and the invulnerability observed in this study of cholinergic interneurons is similar to that observed in HD. The vulnerability of the SS/NPY interneurons to QA is, however, in stark contrast to their invulnerability in HD. The results thus suggest that although the excitotoxin hypothesis of striatal neuron death in HD has merit, QA injections into adult rat striatum do not strictly mimic the outcome in HD. This suggests that either adult rats are not a completely suitable subject for mimicking HD or the HD excitotoxic process does not involve a freely circulating excitotoxin such as QA.",
author = "G. Figueredo-Cardenas and Anderson, {K. D.} and Q. Chen and Veenman, {C. L.} and Anton Reiner",
year = "1994",
month = "1",
day = "1",
doi = "10.1006/exnr.1994.1145",
language = "English (US)",
volume = "129",
pages = "37--56",
journal = "Experimental Neurology",
issn = "0014-4886",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Relative survival of striatal projection neurons and interneurons after intrastriatal injection of quinolinic acid in rats

AU - Figueredo-Cardenas, G.

AU - Anderson, K. D.

AU - Chen, Q.

AU - Veenman, C. L.

AU - Reiner, Anton

PY - 1994/1/1

Y1 - 1994/1/1

N2 - An excitotoxic process mediated by the NMDA type glutamate receptor may be involved in striatal neuron death in Huntington’s disease (HD). To explore this possibility, we have injected an NMDA-receptor-specific excitotoxin, quinolinic acid (QA), into the striatum in adult rats and 2-4 months postlesion explored the relative patterns of survival for the various different types of striatal projection neurons and interneurons and for the striatal efferent fibers in the different striatal projection areas. The perikarya of specific types of striatal neurons were identified by neurotransmitter immunohistochemical labeling or by retrograde labeling from striatal target areas, while the striatal efferent fiber plexuses were identified by neurotransmitter immunohistochemical labeling. The pattern of survival for the perikarya of each neuron type as a function of distance from the center of the injection site was determined, and the relative survival of each type was compared. For the fibers in target areas, computer-assisted image analysis was used to determine the degree of fiber loss for each projection target. In the study of perikaryal vulnerability, we found that the somatostatin-neuropeptide Y (SS/NPY) interneurons were the most vulnerable to QA and the cholinergic neurons were invulnerable to QA. The perikarya of all projection neuron types (striatopallidal, striatonigral, and striato-entopeduncular) were less vulnerable than the SS/NPY interneurons and more vulnerable than the cholinergic interneurons. Among projection neuron perikarya, there was evidence of differential vulnerability, with striatonigral neurons appearing to be the most vulnerable. Examination of immunolabeled striatal fibers in the striatal target areas indicated that striato-entopeduncular fibers better survived intrastriatal QA than did striatopallidal or striatonigral fibers. The apparent order of vulnerability observed in this study among projection neurons and/or their efferent fiber plexuses and the invulnerability observed in this study of cholinergic interneurons is similar to that observed in HD. The vulnerability of the SS/NPY interneurons to QA is, however, in stark contrast to their invulnerability in HD. The results thus suggest that although the excitotoxin hypothesis of striatal neuron death in HD has merit, QA injections into adult rat striatum do not strictly mimic the outcome in HD. This suggests that either adult rats are not a completely suitable subject for mimicking HD or the HD excitotoxic process does not involve a freely circulating excitotoxin such as QA.

AB - An excitotoxic process mediated by the NMDA type glutamate receptor may be involved in striatal neuron death in Huntington’s disease (HD). To explore this possibility, we have injected an NMDA-receptor-specific excitotoxin, quinolinic acid (QA), into the striatum in adult rats and 2-4 months postlesion explored the relative patterns of survival for the various different types of striatal projection neurons and interneurons and for the striatal efferent fibers in the different striatal projection areas. The perikarya of specific types of striatal neurons were identified by neurotransmitter immunohistochemical labeling or by retrograde labeling from striatal target areas, while the striatal efferent fiber plexuses were identified by neurotransmitter immunohistochemical labeling. The pattern of survival for the perikarya of each neuron type as a function of distance from the center of the injection site was determined, and the relative survival of each type was compared. For the fibers in target areas, computer-assisted image analysis was used to determine the degree of fiber loss for each projection target. In the study of perikaryal vulnerability, we found that the somatostatin-neuropeptide Y (SS/NPY) interneurons were the most vulnerable to QA and the cholinergic neurons were invulnerable to QA. The perikarya of all projection neuron types (striatopallidal, striatonigral, and striato-entopeduncular) were less vulnerable than the SS/NPY interneurons and more vulnerable than the cholinergic interneurons. Among projection neuron perikarya, there was evidence of differential vulnerability, with striatonigral neurons appearing to be the most vulnerable. Examination of immunolabeled striatal fibers in the striatal target areas indicated that striato-entopeduncular fibers better survived intrastriatal QA than did striatopallidal or striatonigral fibers. The apparent order of vulnerability observed in this study among projection neurons and/or their efferent fiber plexuses and the invulnerability observed in this study of cholinergic interneurons is similar to that observed in HD. The vulnerability of the SS/NPY interneurons to QA is, however, in stark contrast to their invulnerability in HD. The results thus suggest that although the excitotoxin hypothesis of striatal neuron death in HD has merit, QA injections into adult rat striatum do not strictly mimic the outcome in HD. This suggests that either adult rats are not a completely suitable subject for mimicking HD or the HD excitotoxic process does not involve a freely circulating excitotoxin such as QA.

UR - http://www.scopus.com/inward/record.url?scp=0028114866&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028114866&partnerID=8YFLogxK

U2 - 10.1006/exnr.1994.1145

DO - 10.1006/exnr.1994.1145

M3 - Article

VL - 129

SP - 37

EP - 56

JO - Experimental Neurology

JF - Experimental Neurology

SN - 0014-4886

IS - 1

ER -