Unilateral eyeball enucleation differentially alters AMPA-, NMDA- and kainate glutamate receptor binding in the newborn rat brain.
The aim of the present work was to evaluate the neurochemical effects of early unilateral visual deprivation as a model of impaired visual maturation. For this purpose, binding to the different ionotropic glutamate receptor subtypes was quantified in vision-related and vision-unrelated brain structures of control and unilaterally deprived newborn rats. At post-natal (PN) day 10, male Sprague-Dawley rats underwent either unilateral eyeball enucleation (enucleation group, n = 12) or sham operation (control group, n = 12). In each group, brains were obtained either at post-natal day 20 (n = 6) or post-natal day 30 (n = 6) and processed for quantitative in vitro autoradiography selective for NMDA, kainate, and AMPA glutamate-binding sites, as well as for the presynaptic adenosine A1 receptor as a control of the deafferentation efficacy. In control animals, quantitative autoradiography revealed an increase in NMDA (e.g. +45% in superior colliculus) and kainate receptor binding (e.g. +55% in visual cortex, layer IV) from post-natal day 20 to post-natal day 30, associated with stable levels of AMPA receptor binding, in the vision-related structures. In the deafferented visual structures, monocular enucleation induced a marked decrease in A1 site density (e.g. -38 to -52%, in the superficial layer of superior colliculi, at PN day 20 and PN day 30, respectively) in parallel with a mild increase in both NMDA (e.g. +8 to 9%, in superior colliculi and visual cortex, layer IV at PN day 30, respectively) and AMPA (e.g. +16%, in layer IV of the visual cortex at PN day 30). Superimposed on marked bilateral decreases at PN day 30 in the enucleated rats, kainate receptor binding also revealed a slight but significant decrease (-5%) in the deafferented superior colliculus as compared to the non-deafferented side. The present findings (different time-courses of, and differential effects of deafferentation on, the NMDA, kainate and AMPA glutamate receptor subtypes throughout the visual brain structures) further support the involvement of these receptors in distinctive roles during maturation of the visual system.
Kiyosawa
M
M
Department of Ophthalmology, School of Medicine, Tokyo Medical and Dental University, Japan. m.kiyosawa.oph@med.tmd.ac.jp
Dauphin
F
F
Kawasaki
T
T
Rioux
P
P
Tokoro
T
T
MacKenzie
E T
ET
Baron
J C
JC
D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D015353:Eye Enucleation; D007608:Kainic Acid / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D014793:Visual Cortex / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D007608:Kainic Acid; D016202:N-Methylaspartate; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D018047:Receptors, Purinergic P1; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid