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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-10-21
pubmed:abstractText
The long-term effects of intrastriatal injections of the agonist of N-methyl-D-aspartate receptors, quinolinic acid, have been extensively characterized. Much less is known, however, about the early molecular and neurochemical changes which occur within a few hours of the toxin injection. In the present study, we have performed intrastriatal injections of low doses of quinolinic acid which induce DNA damage 10-12 h post-lesion, and selective death of striatal projection neurons two weeks later. We examined the time-course of alterations in the microtubule-associated protein 2, an early marker of cytoskeletal disruption, and enkephalin and substance P, two neuropeptides present in largely distinct subpopulations of striatal efferent neurons projecting to the globus pallidus and entopeduncular nucleus, respectively. Immunoreactivity for microtubule-associated protein 2 was decreased at the periphery of the lesion 10 h after quinolinate injection. Levels of enkephalin messenger RNA were markedly decreased as early as 6 h post-lesion; however, a significant decrease in enkephalin immunoreactivity was not observed in the globus pallidus (external pallidum) until 12 h post-injection. Levels of substance P messenger RNA were decreased 12 h post-injection in striatal neurons. However, in contrast to enkephalin immunoreactivity, immunolabeling for substance P was not significantly decreased at this time-point in the internal pallidum, a finding reminiscent of early grades of Huntington's disease. The results reveal the time-course of change in messenger RNA and peptide levels in striatal efferent neurons shortly after an excitotoxic insult. These data have implications for the interpretation of findings in post mortem brain and mouse models of Huntington's disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
843-53
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed-meshheading:10473250-Animals, pubmed-meshheading:10473250-Basal Ganglia, pubmed-meshheading:10473250-Corpus Striatum, pubmed-meshheading:10473250-Cytoskeleton, pubmed-meshheading:10473250-DNA Damage, pubmed-meshheading:10473250-Disease Models, Animal, pubmed-meshheading:10473250-Efferent Pathways, pubmed-meshheading:10473250-Enkephalins, pubmed-meshheading:10473250-Excitatory Amino Acid Agonists, pubmed-meshheading:10473250-Globus Pallidus, pubmed-meshheading:10473250-Huntington Disease, pubmed-meshheading:10473250-Injections, pubmed-meshheading:10473250-Male, pubmed-meshheading:10473250-Mice, pubmed-meshheading:10473250-Mice, Neurologic Mutants, pubmed-meshheading:10473250-Microtubule-Associated Proteins, pubmed-meshheading:10473250-Nerve Tissue Proteins, pubmed-meshheading:10473250-Neurons, pubmed-meshheading:10473250-Quinolinic Acid, pubmed-meshheading:10473250-RNA, Messenger, pubmed-meshheading:10473250-Rats, pubmed-meshheading:10473250-Rats, Sprague-Dawley, pubmed-meshheading:10473250-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:10473250-Substance P
pubmed:year
1999
pubmed:articleTitle
Early effects of intrastriatal injections of quinolinic acid on microtubule-associated protein-2 and neuropeptides in rat basal ganglia.
pubmed:affiliation
Department of Pharmacology, University of Pennsylvania, Philadelphia 19104, USA.
pubmed:publicationType
Journal Article