NMDA-NR1 and AMPA-GluR4 receptor subunit immunoreactivities in the absence epileptic WAG/Rij rat.
From an age of 2-3 months onwards, the WAG/Rij rat, a genetic model for absence epilepsy, develops spike-wave discharges (SWD). SWD start in the peri-oral somatosensory cortex (POsc), whereas the rostral reticular thalamic nucleus (rRTN) contributes to synchronizing the thalamo-cortical oscillations. We hypothesize that N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptors in the POsc and rRTN are involved in, respectively, the initiation and synchronization of SWD activity. As a first step to test this hypothesis, 3 months old non-epileptic and 6 months old absence epileptic WAG/Rij rats were compared with age-matched non-epileptic ACI control rats. The presence of NMDA and AMPA receptors was assessed by quantifying immunostaining for the NMDA-NR1 subunit and the AMPA-GluR4 subunit, respectively. In the POsc, WAG/Rij rats of both ages showed less NMDA-NR1 (-14.7%) and AMPA-GluR4 (-8.7%) subunit staining than ACI rats. From 3 to 6 months, AMPA-GluR4 subunit staining more strongly increased in the rRTN of WAG/Rij rats than of ACI rats. Further studies should support our assumption that in the POsc of the WAG/Rij rat, SWD start as a result of reduced NMDA- and AMPA-mediated glutamatergic stimulation, and that AMPA-GluR4 containing neurons in the rRTN of this rat strain contribute to synchronization of thalamic and cortical neurons.
van de Bovenkamp-Janssen
Maartje C
MC
Department of Cellular Animal Physiology, Institute for Neuroscience, Radboud University Nijmegen, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands.
van der Kloet
Joeri C
JC
van Luijtelaar
Gilles
G
Roubos
Eric W
EW
D000375:Aging / Q000502:physiology; D000818:Animals; D020643:Anterior Thalamic Nuclei / Q000378:metabolism*; D004195:Disease Models, Animal; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism*; D051381:Rats; D011912:Rats, Inbred ACI; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013003:Somatosensory Cortex / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism*
C409466:NR1 NMDA receptor; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C104724:glutamate receptor ionotropic, AMPA 4; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid