Characterization of striatal cultures with the effect of QUIN and NMDA.
The degeneration of selective and specific types of neurons is a characteristic feature in several neurodegenerative disorders. N-methyl-D-aspartate receptor (NMDAR) agonist quinolinic acid (QUIN)-induced excitotoxicity has been implicated in neurodegeneration and mimics Huntington's disease (HD) by the loss of medium-sized spiny projection neurons while sparing medium-sized aspiny interneurons in the striatum. Previous work suggests that somatostatin/neuropeptide Y (SST/NPY)-containing neurons are selectively preserved in HD due to the presence of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) and the lack of NMDAR. In the present study, the distribution of somatostatin (SST), neuropeptide Y (NPY), nitric oxide synthase (nNOS), NMDA receptor type-1 (NR1), and the enzyme NADPH-d was determined in cultured striatal neurons with the effect of QUIN and N-methyl-D-aspartate (NMDA). SST/NPY-positive neurons, which constitute approximately 8-10% of striatal neurons, are selectively spared in QUIN/NMDA-treated cultures. nNOS and NADPH-d-positive neurons, comprising 3.8% of the neuronal population, also exhibit selective resistance to excitotoxicity. Most NR1-positive neurons, which constitute >80% of the total neuronal population, are lost in majority upon treatment with QUIN and NMDA. SST and NADPH-d-positive neurons also colocalize with Cu/Zn superoxide dismutase (Cu/Zn SOD). In conclusion, our results thus demonstrate that SST/NPY/nNOS-positive neurons are selectively spared in NMDA agonist-induced excitotoxicity, which could be attributed to the presence of Cu/Zn SOD and NADPH-d in addition to the low abundance of NMDAR on these neurons.
Kumar
Ujendra
U
Fraser Laboratories, Department of Medicine, Room M3-15, Royal Victoria Hospital, McGill University, 687 Pine Avenue West, Montreal, Que., Canada H3A 1A1. ujendra.kumar@muhc.mcgill.ca
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D016202:N-Methylaspartate / Q000494:pharmacology*; D009249:NADP / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D018690:Excitatory Amino Acid Agonists; C409466:NR1 NMDA receptor; D009478:Neuropeptide Y; D016194:Receptors, N-Methyl-D-Aspartate; D013004:Somatostatin; D009249:NADP; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D013482:Superoxide Dismutase; D017378:Quinolinic Acid