Glutamate receptor agonist kainate enhances primary dendrite number and length from immature mouse cortical neurons in vitro.
Glutamate is an important regulator of dendrite development that may inhibit, (during ischemic injury), or facilitate (during early development) dendrite growth. Previous studies have reported mainly on the N-methyl-D-aspartate (NMDA) receptor-mediated dendrite growth-promoting effect of glutamate. In this study, we examined how the non-NMDA receptor agonist kainate influenced dendrite growth. E18 mouse cortical neurons were grown for 3 days in vitro and immunolabeled with anti-microtubule-associated protein 2 (MAP2) and anti-neurofilament (NF-H), to identify dendrites and axons, respectively. Exposure of cortical neurons to kainate increased dendrite growth without affecting neuron survival. This effect was dose-dependent, reversible and blocked by the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA)/kainate receptor antagonist NBQX and the low-affinity kainate receptor antagonist NS-102, but not by the AMPA receptor antagonist CFM-2. In addition, the NMDA receptor antagonist MK-801 had no effect on kainate-induced dendrite growth. Immunolabeling and Western blot analysis of kainate receptors using antibodies against the GluR6 and KA2 subunits, demonstrated that the immature cortical neurons used in this study express kainate receptor proteins. These results suggest that kainate-induced non-NMDA receptor activation promotes dendrite growth, and in particular primary dendrite number and length, from immature cortical neurons in vitro, and that kainate receptors may be directly involved in this process. Furthermore, these data support the possibility that like NMDA receptors, kainate receptor activation may also contribute to early neurite growth from cortical neurons in vitro.
Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19107, USA.
Hubert
H
Monnerie
Peter D
PD
Le Roux
D000818:Animals; D001369:Axons / Q000187:drug effects; D001570:Benzodiazepinones / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology; D003712:Dendrites / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D010091:Oximes / Q000494:pharmacology; D018092:Kainic Acid Receptors / Q000378:metabolism; D013997:Time Factors
D001570:Benzodiazepinones; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D007608:Kainic Acid; D010091:Oximes; D018092:Kainic Acid Receptors; C119033:CFM 2; C084273:5-nitro-6,7,8,9-tetrahydrobenzo(G)indole-2,3-dione-3-oxime