title: Age-dependent differences in survival of striatal somatostatin-NPY-NADPH-diaphorase-containing interneurons versus striatal projection neurons after intrastriatal injection of quinolinic acid in rats.
abstract: Some authors have reported greater sparing of neurons containing somatostatin (SS)-neuropeptide Y (NPY)-NADPH-diaphorase (NADPHd) than projection neurons after intrastriatal injection of quinolinic acid (QA), an excitotoxin acting at NMDA receptors. Such findings have been used to support the NMDA receptor excitotoxin hypothesis of Huntington's disease (HD) and to claim that intrastriatal QA produces an animal model of HD. Other studies have, however, reported that SS/NPY/NADPHd interneurons are highly vulnerable to QA. We examined the influence of animal age (young versus mature), QA concentration (225 mM versus 50 mM), and injection speed (3 min versus 15 min) on the relative SS/NPY/NADPHd neuron survival in eight groups of rats that varied along these parameters to determine the basis of such prior discrepancies. Two weeks after QA injection, we analyzed the relative survival of neurons labeled by NADPHd histochemistry, SS/NPY immunohistochemistry, or cresyl violet staining (which stains all striatal neurons, the majority of which are projection neurons) in the so-called lesion transition zone (i.e., the zone of 40-60% neuronal survival). We found that age, and to a lesser extent injection speed, had a significant effect on relative SS/NPY/NADPHd interneuron survival. The NADPHd- and SS/NPY-labeled neurons typically survived better than projection neurons in young rats and more poorly in mature rats. This trend was greatly accentuated with fast QA injection. Age-related differences may be attributable to declines in projection neuron sensitivity to QA with age. Since rapid QA injections result in excitotoxin efflux, we interpret the effect of injection speed to suggest that brief exposure to a large dose of QA (with fast injection) may better accentuate the differential vulnerabilities of NADPHd/SS/NPY interneurons and projection neurons than does exposure to the same total amount of QA delivered more gradually (slow injection). These findings reconcile the discordant results found by previous authors and suggest that QA injected into rat striatum does reproduce the neurochemical traits of HD under some circumstances. These findings are consistent with a role of excitotoxicity in HD pathogenesis, and they also have implications for the basis of the more pernicious nature of striatal neuron loss in juvenile onset HD.
authors.affiliation: Department of Anatomy and Neurobiology, The University of Tennessee Health Sciences Center, Memphis 38163, USA.
authors.forename: G
authors.initials: G
authors.lastname: Figueredo-Cardenas
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Reiner
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002470:Cell Survival; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D007267:Injections; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000378:metabolism*; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D009478:Neuropeptide Y; D013004:Somatostatin; D009252:NADPH Dehydrogenase; D017378:Quinolinic Acid