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Slow and selective death of spinal motor neurons in vivo by intrathecal infusion of kainic acid: implications for AMPA receptor-mediated excitotoxicity in ALS.
J Neurochem. 2006 Aug; 98(3):782-91.JN

Abstract

Excitotoxicity mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors has been proposed to play a major role in the selective death of motor neurons in sporadic amyotrophic lateral sclerosis (ALS), and motor neurons are more vulnerable to AMPA receptor-mediated excitotoxicity than are other neuronal subclasses. On the basis of the above evidence, we aimed to develop a rat model of ALS by the long-term activation of AMPA receptors through continuous infusion of kainic acid (KA), an AMPA receptor agonist, into the spinal subarachnoid space. These rats displayed a progressive motor-selective behavioral deficit with delayed loss of spinal motor neurons, mimicking the clinicopathological characteristics of ALS. These changes were significantly ameliorated by co-infusion with 6-nitro-7-sulfamobenso(f)quinoxaline-2,3-dione (NBQX), but not with d(-)-2-amino-5-phosphonovaleric acid (APV), and were exacerbated by co-infusion with cyclothiazide, indicative of an AMPA receptor-mediated mechanism. Among the four AMPA receptor subunits, expression of GluR3 mRNA was selectively up-regulated in motor neurons but not in dorsal horn neurons of the KA-infused rats. The up-regulation of GluR3 mRNA in this model may cause a molecular change that induces the selective vulnerability of motor neurons to KA by increasing the proportion of GluR2-lacking (i.e. calcium-permeable) AMPA receptors. This rat model may be useful in investigating ALS etiology.

Authors+Show Affiliations

Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16893420

Citation

Sun, Hui, et al. "Slow and Selective Death of Spinal Motor Neurons in Vivo By Intrathecal Infusion of Kainic Acid: Implications for AMPA Receptor-mediated Excitotoxicity in ALS." Journal of Neurochemistry, vol. 98, no. 3, 2006, pp. 782-91.
Sun H, Kawahara Y, Ito K, et al. Slow and selective death of spinal motor neurons in vivo by intrathecal infusion of kainic acid: implications for AMPA receptor-mediated excitotoxicity in ALS. J Neurochem. 2006;98(3):782-91.
Sun, H., Kawahara, Y., Ito, K., Kanazawa, I., & Kwak, S. (2006). Slow and selective death of spinal motor neurons in vivo by intrathecal infusion of kainic acid: implications for AMPA receptor-mediated excitotoxicity in ALS. Journal of Neurochemistry, 98(3), 782-91.
Sun H, et al. Slow and Selective Death of Spinal Motor Neurons in Vivo By Intrathecal Infusion of Kainic Acid: Implications for AMPA Receptor-mediated Excitotoxicity in ALS. J Neurochem. 2006;98(3):782-91. PubMed PMID: 16893420.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Slow and selective death of spinal motor neurons in vivo by intrathecal infusion of kainic acid: implications for AMPA receptor-mediated excitotoxicity in ALS. AU - Sun,Hui, AU - Kawahara,Yukio, AU - Ito,Kyoko, AU - Kanazawa,Ichiro, AU - Kwak,Shin, PY - 2006/8/9/pubmed PY - 2006/9/9/medline PY - 2006/8/9/entrez SP - 782 EP - 91 JF - Journal of neurochemistry JO - J Neurochem VL - 98 IS - 3 N2 - Excitotoxicity mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors has been proposed to play a major role in the selective death of motor neurons in sporadic amyotrophic lateral sclerosis (ALS), and motor neurons are more vulnerable to AMPA receptor-mediated excitotoxicity than are other neuronal subclasses. On the basis of the above evidence, we aimed to develop a rat model of ALS by the long-term activation of AMPA receptors through continuous infusion of kainic acid (KA), an AMPA receptor agonist, into the spinal subarachnoid space. These rats displayed a progressive motor-selective behavioral deficit with delayed loss of spinal motor neurons, mimicking the clinicopathological characteristics of ALS. These changes were significantly ameliorated by co-infusion with 6-nitro-7-sulfamobenso(f)quinoxaline-2,3-dione (NBQX), but not with d(-)-2-amino-5-phosphonovaleric acid (APV), and were exacerbated by co-infusion with cyclothiazide, indicative of an AMPA receptor-mediated mechanism. Among the four AMPA receptor subunits, expression of GluR3 mRNA was selectively up-regulated in motor neurons but not in dorsal horn neurons of the KA-infused rats. The up-regulation of GluR3 mRNA in this model may cause a molecular change that induces the selective vulnerability of motor neurons to KA by increasing the proportion of GluR2-lacking (i.e. calcium-permeable) AMPA receptors. This rat model may be useful in investigating ALS etiology. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/16893420/Slow_and_selective_death_of_spinal_motor_neurons_in_vivo_by_intrathecal_infusion_of_kainic_acid:_implications_for_AMPA_receptor_mediated_excitotoxicity_in_ALS_ L2 - https://doi.org/10.1111/j.1471-4159.2006.03903.x DB - PRIME DP - Unbound Medicine ER -