Positive and negative modulation by AMPA- and kainate-receptors of striatal kainate injection-induced neuronal loss in rat forebrain.
We investigated the roles of ionotropic glutamate receptor subtypes in mediating striatal kainate injection-induced neuronal loss in rat forebrain, using subtype-specific antagonists and histochemical staining. Our study demonstrates that kainate injected unilaterally into the striatum induces a massive neuronal loss in the rat ipsilateral forebrain through activation of kainate receptors and, to a limited extent, a consequent involvement of M-methyl-D-aspartate (NMDA) receptors, whereas activation of alpha-amino-3-hydroxy-5-methylisoxazol-4-propionate (AMPA) receptors shows a neuroprotective effect. These and previous results suggest that three subtypes of ionotropic glutamate receptors play differential roles in mediating excitatory amino acid (EAA)-induced neurodegeneration.
Zhu
X
X
Department of Pharmacology, Faculty of Medicine, The National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260.
Jin
S
S
Ng
Y K
YK
Lee
W L
WL
Wong
P T
PT
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D004347:Drug Interactions / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000378:metabolism* / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007608:Kainic Acid; D018696:Neuroprotective Agents; D009498:Neurotoxins; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate